Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1

PubMed Central

2014-01-01

Background Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor specific stem cell marker in colorectal and pancreatic cancer. Previous in vitro and in vivo studies have demonstrated the therapeutic effects of inhibiting DCLK1 with small interfering RNA (siRNA) as well as genetically targeting the DCLK1+ cell for deletion. However, the effects of inhibiting DCLK1 kinase activity have not been studied directly. Therefore, we assessed the effects of inhibiting DCLK1 kinase activity using the novel small molecule kinase inhibitor, LRRK2-IN-1, which demonstrates significant affinity for DCLK1. Results Here we report that LRRK2-IN-1 demonstrates potent anti-cancer activity including inhibition of cancer cell proliferation, migration, and invasion as well as induction of apoptosis and cell cycle arrest. Additionally we found that it regulates stemness, epithelial-mesenchymal transition, and oncogenic targets on the molecular level. Moreover, we show that LRRK2-IN-1 suppresses DCLK1 kinase activity and downstream DCLK1 effector c-MYC, and demonstrate that DCLK1 kinase activity is a significant factor in resistance to LRRK2-IN-1. Conclusions Given DCLK1’s tumor stem cell marker status, a strong understanding of its biological role and interactions in gastrointestinal tumors may lead to discoveries that improve patient outcomes. The results of this study suggest that small molecule inhibitors of DCLK1 kinase should be further investigated as they may hold promise as anti-tumor stem cell drugs. PMID:24885928

Streamlined design and self reliant hardware for active control of precision space structures

NASA Technical Reports Server (NTRS)

Hyland, David C.; King, James A.; Phillips, Douglas J.

1994-01-01

Precision space structures may require active vibration control to satisfy critical performance requirements relating to line-of-sight pointing accuracy and the maintenance of precise, internal alignments. In order for vibration control concepts to become operational, it is necessary that their benefits be practically demonstrated in large scale ground-based experiments. A unique opportunity to carry out such demonstrations on a wide variety of experimental testbeds was provided by the NASA Control-Structure Integration (CSI) Guest Investigator (GI) Program. This report surveys the experimental results achieved by the Harris Corporation GI team on both Phases 1 and 2 of the program and provides a detailed description of Phase 2 activities. The Phase 1 results illustrated the effectiveness of active vibration control for space structures and demonstrated a systematic methodology for control design, implementation test. In Phase 2, this methodology was significantly streamlined to yield an on-site, single session design/test capability. Moreover, the Phase 2 research on adaptive neural control techniques made significant progress toward fully automated, self-reliant space structure control systems. As a further thrust toward productized, self-contained vibration control systems, the Harris Phase II activity concluded with experimental demonstration of new vibration isolation hardware suitable for a wide range of space-flight and ground-based commercial applications.The CSI GI Program Phase 1 activity was conducted under contract NASA1-18872, and the Phase 2 activity was conducted under NASA1-19372.

Antibody-Dependent Cell-Mediated Cytotoxicity Effector-Enhanced EphA2 Agonist Monoclonal Antibody Demonstrates Potent Activity against Human Tumors1

PubMed Central

Bruckheimer, Elizabeth M; Fazenbaker, Christine A; Gallagher, Sandra; Mulgrew, Kathy; Fuhrmann, Stacy; Coffman, Karen T; Walsh, William; Ready, Shannon; Cook, Kim; Damschroder, Melissa; Kinch, Michael; Kiener, Peter A; Woods, Rob; Gao, Changshou; Dall'Acqua, William; Wu, Herren; Coats, Steven

2009-01-01

EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vitro and in vivo antibody-dependent cell-mediated cytotoxicity (ADCC) activity of EphA2 effector-enhanced agonist monoclonal antibodies was evaluated. With tumor cell lines and healthy human peripheral blood monocytes, the EphA2 antibodies demonstrated ∼80% tumor cell killing. In a dose-dependent manner, natural killer (NK) cells were required for the in vitro ADCC activity and became activated as demonstrated by the induction of cell surface expression of CD107a. To assess the role of NK cells on antitumor efficacy in vivo, the EphA2 antibodies were evaluated in xenograft models in severe compromised immunodeficient (SCID) mice (which have functional NK cells and monocytes) and SCID nonobese diabetic (NOD) mice (which largely lack functional NK cells and monocytes). Dosing of EphA2 antibody in the SCID murine tumor model resulted in a 6.2-fold reduction in tumor volume, whereas the SCID/nonobese diabetic model showed a 1.6-fold reduction over the isotype controls. Together, these results demonstrate that the anti-EphA2 monoclonal antibodies may function through at least two mechanisms of action: EphA2 receptor activation and ADCC-mediated activity. These novel EphA2 monoclonal antibodies provide additional means by which host effector mechanisms can be activated for selective destruction of EphA2-expressing tumor cells. PMID:19484140

Effects of alpha-2 agonists on renal function in hypertensive humans.

PubMed

Goldberg, M; Gehr, M

1985-01-01

Centrally acting adrenergic agonists, by decreasing peripheral adrenergic activity, are effective antihypertensive agents. The older agents, however, especially methyldopa, have been associated with weight gain, clinical edema, and antihypertensive tolerance when used as monotherapy. While acute studies in humans have demonstrated weight gain and sodium retention with clonidine and guanabenz, chronic administration results in a decrease in weight and plasma volume. The absence of chronic weight gain and of sodium retention could be the result of a counterbalance between hypotension-related antinatriuresis, secondary to a decrease in glomerular filtration rate and renal blood flow, and natriuretic activity, as a result of a decrease in renal sympathetic tone. Whereas natriuresis and water diuresis have been demonstrated in animals with acute clonidine or guanabenz administration, this has not been demonstrated in humans. Recent studies in which saline administration was used to precondition humans to a subsequent natriuretic stimulus (i.e., guanabenz-induced decreased renal adrenergic activity) resulted in stabilization of renal blood flow and natriuresis. Selective reduction renal sympathetic activity affecting salt and water transport may explain why guanabenz and probably also clonidine seem to be devoid of the sodium/fluid-retaining properties that are common with other antihypertensive agents. Because agents of this class have effects other than pure central alpha-2 agonism (such as alpha-1 activity), they might have confounding and counterbalancing side effects leading to sodium and water retention.

Localized, Non-Harmonic Active Flap Motions for Low Frequency In-Plane Rotor Noise Reduction

NASA Technical Reports Server (NTRS)

Sim, Ben W.; Potsdam, Mark; Kitaplioglu, Cahit; LeMasurier, Philip; Lorber, Peter; Andrews, Joseph

2012-01-01

A first-of-its-kind demonstration of the use of localized, non-harmonic active flap motions, for suppressing low frequency, in-plane rotor noise, is reported in this paper. Operational feasibility is verified via testing of the full-scale AATD/Sikorsky/UTRC active flap demonstration rotor in the NFAC's 40- by 80-Foot anechoic wind tunnel. Effectiveness of using localized, non-harmonic active flap motions are compared to conventional four-per-rev harmonic flap motions, and also active flap motions derived from closed-loop acoustics implementations. All three approaches resulted in approximately the same noise reductions over an in-plane three-by-three microphone array installed forward and near in-plane of the rotor in the nearfield. It is also reported that using an active flap in this localized, non-harmonic manner, resulted in no more that 2% rotor performance penalty, but had the tendency to incur higher hub vibration levels.

Fostering young children's interest in numeracy through demonstration of its value: the Footsteps Study

NASA Astrophysics Data System (ADS)

Colliver, Yeshe

2017-07-01

Children's early mathematical abilities are fundamental to their later academic achievement. An interest in mathematics in the early years is likely to establish a positive attitude to later mathematical learning, hopefully sustaining continued interest in mathematics and mathematical learning. Approaches to early mathematics teaching in the early years, however, are typically adult-initiated, which may fail to capture children's interest. Given the importance of children's motivation and sustained interest, the study described here strove to spark children's interests in mathematical problems in everyday life. The study sought to determine if children would incorporate more numeracy-related concepts into their free play if exposed to adult demonstrations of age-appropriate numeracy activities such as patterning. For at least 15 min three times weekly, participating children's parents and educators demonstrated numeracy problem-solving nearby, while children engaged in other activities. Demonstrations were thought to ascribe social value to the problem-solving activities. If children became interested in participating, adults told them to wait until the demonstrations finished, further indicating social value. Results show these children chose to play with numeracy-related activities in their free play time at preschool significantly more than children in a control group. These results suggest that seeking to foster children's interest in mathematics through child-initiated play, rather than prescribing adult-initiated mathematics activities, may be an important means of laying the foundation for lifelong mathematics learning. Ascribing social value to numeracy applications is proposed as a new approach to teaching mathematics in the early years.

Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite.

PubMed

Ricciardi, M R; Licchetta, R; Mirabilii, S; Scarpari, M; Parroni, A; Fabbri, A A; Cescutti, P; Reverberi, M; Fanelli, C; Tafuri, A

2017-01-01

Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor , on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity.

Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite

PubMed Central

Scarpari, M.; Parroni, A.; Fabbri, A. A.; Cescutti, P.; Reverberi, M.; Fanelli, C.

2017-01-01

Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor, on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity. PMID:29270245

DEMONSTRATION OF SORBENT INJECTION TECHNOLOGY ON A TANGENTIALLY COAL-FIRED UTILITY BOILER (YORKTOWN LIMB DEMONSTRATION)

EPA Science Inventory

The report summarizes activities conducted and results achieved in an EPA-sponsored program to demonstrate Limestone Injection Multistage Burner (LIMB) technology on a tangentially fired coal-burning utility boiler, Virginia Power's 180-MWe Yorktown Unit No. 2. his successfully d...

Analysis and optimization of the active rigidity joint

NASA Astrophysics Data System (ADS)

Manzo, Justin; Garcia, Ephrahim

2009-12-01

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

Active vibration control testing of the SPICES program: final demonstration article

NASA Astrophysics Data System (ADS)

Dunne, James P.; Jacobs, Jack H.

1996-05-01

The Synthesis and Processing of Intelligent Cost Effective Structures (SPICES) Program is a partnership program sponsored by the Advanced Research Projects Agency. The mission of the program is to develop cost effective material processing and synthesis technologies to enable new products employing active vibration suppression and control devices to be brought to market. The two year program came to fruition in 1995 through the fabrication of the final smart components and testing of an active plate combined with two trapezoidal rails, forming an active mount. Testing of the SPICES combined active mount took place at McDonnell Douglas facilities in St. Louis, MO, in October-December 1995. Approximately 15 dB reduction in overall response of a motor mounted on the active structure was achieved. Further details and results of the SPICES combined active mount demonstration testing are outlined. Results of numerous damping and control strategies that were developed and employed in the testing are presented, as well as aspects of the design and fabrication of the SPICES active mount components.

From a marine neuropeptide to antimicrobial pseudopeptides containing aza-β(3)-amino acids: structure and activity

PubMed Central

Laurencin, Mathieu; Legrand, Baptiste; Duval, Emilie; Henry, Joël; Baudy-Floc'H, Michèle; Zatylny-Gaudin, Céline; Bondon, Arnaud

2012-01-01

Incorporation of aza-β3-amino acids into endogenous neuropeptide from mollusks (ALSGDAFLRF-NH2) with weak antimicrobial activities allows us to design new AMPs sequences. We find that, depending on the nature of the substitution, these could result either in inactive pseudopeptides or in a drastic enhancement of the antimicrobial activity without high cytotoxicity resulted. Structural studies perform by NMR and circular dichroism on the pseudopeptides show the impact of aza-β3-amino acids on the peptide structures. We obtain the first three-dimensional structures of pseudopeptides containing aza-β3-amino acids in aqueous micellar SDS and demonstrate that hydrazino turn can be formed in aqueous solution. Overall, these results demonstrate the ability to modulate AMPs activities through structural modifications induced by the nature and the position of these amino acid analogs in the peptide sequences. PMID:22320306

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop*

PubMed Central

Quintero, Omar A.; Unrath, William C.; Stevens, Stanley M.; Manor, Uri; Kachar, Bechara; Yengo, Christopher M.

2013-01-01

Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells. PMID:24214986

Myosin 3A kinase activity is regulated by phosphorylation of the kinase domain activation loop.

PubMed

Quintero, Omar A; Unrath, William C; Stevens, Stanley M; Manor, Uri; Kachar, Bechara; Yengo, Christopher M

2013-12-27

Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells.

Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

PubMed Central

Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

2010-01-01

Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

Coding stimulus amplitude by correlated neural activity

NASA Astrophysics Data System (ADS)

Metzen, Michael G.; Ávila-Åkerberg, Oscar; Chacron, Maurice J.

2015-04-01

While correlated activity is observed ubiquitously in the brain, its role in neural coding has remained controversial. Recent experimental results have demonstrated that correlated but not single-neuron activity can encode the detailed time course of the instantaneous amplitude (i.e., envelope) of a stimulus. These have furthermore demonstrated that such coding required and was optimal for a nonzero level of neural variability. However, a theoretical understanding of these results is still lacking. Here we provide a comprehensive theoretical framework explaining these experimental findings. Specifically, we use linear response theory to derive an expression relating the correlation coefficient to the instantaneous stimulus amplitude, which takes into account key single-neuron properties such as firing rate and variability as quantified by the coefficient of variation. The theoretical prediction was in excellent agreement with numerical simulations of various integrate-and-fire type neuron models for various parameter values. Further, we demonstrate a form of stochastic resonance as optimal coding of stimulus variance by correlated activity occurs for a nonzero value of noise intensity. Thus, our results provide a theoretical explanation of the phenomenon by which correlated but not single-neuron activity can code for stimulus amplitude and how key single-neuron properties such as firing rate and variability influence such coding. Correlation coding by correlated but not single-neuron activity is thus predicted to be a ubiquitous feature of sensory processing for neurons responding to weak input.

Active tuning of high-Q dielectric metasurfaces

DOE PAGES

Parry, Matthew; Komar, Andrei; Hopkins, Ben; ...

2017-08-02

Here, we demonstrate the active tuning of all-dielectric metasurfaces exhibiting high-quality factor (high-Q) resonances. The active control is provided by embedding the asymmetric silicon meta-atoms with liquid crystals, which allows the relative index of refraction to be controlled through heating. It is found that high quality factor resonances (Q = 270 ± 30) can be tuned over more than three resonance widths. Our results demonstrate the feasibility of using all-dielectric metasurfaces to construct tunable narrow-band filters.

Dynamic restructuring drives catalytic activity on nanoporous gold–silver alloy catalysts

DOE PAGES

Zugic, Branko; Wang, Lucun; Heine, Christian; ...

2016-12-19

Bimetallic, nanostructured materials hold promise for improving catalyst activity and selectivity, yet little is known about the dynamic compositional and structural changes that these systems undergo during pretreatment that leads to efficient catalyst function. Here we use ozone-activated silver–gold alloys in the form of nanoporous gold as a case study to demonstrate the dynamic behaviour of bimetallic systems during activation to produce a functioning catalyst. We show that it is these dynamic changes that give rise to the observed catalytic activity. Advanced in situ electron microscopy and X-ray photoelectron spectroscopy are used to demonstrate that major restructuring and compositional changesmore » occur along the path to catalytic function for selective alcohol oxidation. Transient kinetic measurements correlate the restructuring to three types of oxygen on the surface. The direct influence of changes in surface silver concentration and restructuring at the nanoscale on oxidation activity is demonstrated. Finally, our results demonstrate that characterization of these dynamic changes is necessary to unlock the full potential of bimetallic catalytic materials.« less

Dynamic restructuring drives catalytic activity on nanoporous gold–silver alloy catalysts

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

Zugic, Branko; Wang, Lucun; Heine, Christian

Bimetallic, nanostructured materials hold promise for improving catalyst activity and selectivity, yet little is known about the dynamic compositional and structural changes that these systems undergo during pretreatment that leads to efficient catalyst function. Here we use ozone-activated silver–gold alloys in the form of nanoporous gold as a case study to demonstrate the dynamic behaviour of bimetallic systems during activation to produce a functioning catalyst. We show that it is these dynamic changes that give rise to the observed catalytic activity. Advanced in situ electron microscopy and X-ray photoelectron spectroscopy are used to demonstrate that major restructuring and compositional changesmore » occur along the path to catalytic function for selective alcohol oxidation. Transient kinetic measurements correlate the restructuring to three types of oxygen on the surface. The direct influence of changes in surface silver concentration and restructuring at the nanoscale on oxidation activity is demonstrated. Finally, our results demonstrate that characterization of these dynamic changes is necessary to unlock the full potential of bimetallic catalytic materials.« less

The effect of science demonstrations as a community service activity on pre-service science teachers' teaching practices

NASA Astrophysics Data System (ADS)

Gurel, Derya Kaltakci

2016-03-01

In the scope of this study, pre-service science teachers (PSST) developed and carried out science demonstrations with everyday materials for elementary school students as a community service activity. 17 PSST enrolled in the community services practices course at Kocaeli University comprised the sample of the present study. Community service practices aim to develop consciousness of social responsibility and professional skills, as well as to gain awareness of social and community problems and find solutions for pre-service teachers. With this aim, each PSST developed five science demonstration activities and their brochures during a semester. At the end of the semester, a total of 85 demonstrations were carried out at public elementary schools, which are especially located in socioeconomically poor districts of Kocaeli, Turkey. In the present case study, the effect of developing and carrying out science demonstrations for elementary school students on six of the PSST' teaching practices on density and buoyancy concept was investigated. 30-minute interviews conducted with each PSST, videos recorded during their demonstration performances, brochures they prepared for their demonstration activities, and reflection papers were used as data collection tools of the study. The results showed that community service practices with science demonstrations had positive effects on PSST' science content knowledge and pedagogical content knowledge.

Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells.

PubMed

Jeong, Kwon; Kim, Kiyoon; Kim, Hunsung; Oh, Yoojung; Kim, Seong-Jin; Jo, Yunhee; Choe, Wonchae

2015-06-01

Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions.

Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells

PubMed Central

JEONG, KWON; KIM, KIYOON; KIM, HUNSUNG; OH, YOOJUNG; KIM, SEONG-JIN; JO, YUNHEE; CHOE, WONCHAE

2015-01-01

Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions. PMID:26137159

A DNA Logic Gate Automaton for Detection of Rabies and Other Lyssaviruses.

PubMed

Vijayakumar, Pavithra; Macdonald, Joanne

2017-07-05

Immediate activation of biosensors is not always desirable, particularly if activation is due to non-specific interactions. Here we demonstrate the use of deoxyribozyme-based logic gate networks arranged into visual displays to precisely control activation of biosensors, and demonstrate a prototype molecular automaton able to discriminate between seven different genotypes of Lyssaviruses, including Rabies virus. The device uses novel mixed-base logic gates to enable detection of the large diversity of Lyssavirus sequence populations, while an ANDNOT logic gate prevents non-specific activation across genotypes. The resultant device provides a user-friendly digital-like, but molecule-powered, dot-matrix text output for unequivocal results read-out that is highly relevant for point of care applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis

PubMed Central

Concannon, Caoimhín G.; Tuffy, Liam P.; Weisová, Petronela; Bonner, Helena P.; Dávila, David; Bonner, Caroline; Devocelle, Marc C.; Strasser, Andreas; Ward, Manus W.

2010-01-01

Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate–activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)–only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca2+ deregulation, mitochondrial depolarization, and apoptosis-inducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis. PMID:20351066

Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality and performance

PubMed Central

Paolone, Giovanna; Lee, Theresa M.; Sarter, Martin

2012-01-01

Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred irrespective of whether the SAT was practiced during the light or dark phase or in constant light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark period but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed time performance and, if practiced during the light phase, contributes to a diurnal activity pattern. PMID:22933795

Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality, and performance.

PubMed

Paolone, Giovanna; Lee, Theresa M; Sarter, Martin

2012-08-29

Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed-time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here, we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred regardless of whether the SAT was practiced during the light or dark phase or in constant-light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark phase but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed-time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed-time performance and, if practiced during the light phase, contributes to a diurnal activity pattern.

Validation of a Scalable Solar Sailcraft

NASA Technical Reports Server (NTRS)

Murphy, D. M.

2006-01-01

The NASA In-Space Propulsion (ISP) program sponsored intensive solar sail technology and systems design, development, and hardware demonstration activities over the past 3 years. Efforts to validate a scalable solar sail system by functional demonstration in relevant environments, together with test-analysis correlation activities on a scalable solar sail system have recently been successfully completed. A review of the program, with descriptions of the design, results of testing, and analytical model validations of component and assembly functional, strength, stiffness, shape, and dynamic behavior are discussed. The scaled performance of the validated system is projected to demonstrate the applicability to flight demonstration and important NASA road-map missions.

Classification of activity engagement in individuals with severe physical disabilities using signals of the peripheral nervous system.

PubMed

Kushki, Azadeh; Andrews, Alexander J; Power, Sarah D; King, Gillian; Chau, Tom

2012-01-01

Communication barriers often result in exclusion of children and youth with disabilities from activities and social settings that are essential to their psychosocial development. In particular, difficulties in describing their experiences of activities and social settings hinder our understanding of the factors that promote inclusion and participation of this group of individuals. To address this specific communication challenge, we examined the feasibility of developing a language-free measure of experience in youth with severe physical disabilities. To do this, we used the activity of the peripheral nervous system to detect patterns of psychological arousal associated with activities requiring different patterns of cognitive/affective and interpersonal involvement (activity engagement). We demonstrated that these signals can differentiate among patterns of arousal associated with these activities with high accuracy (two levels: 81%, three levels: 74%). These results demonstrate the potential for development of a real-time, motor- and language-free measure for describing the experiences of children and youth with disabilities.

12 CFR 268.707 - Program accessibility: Existing facilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Programs and Activities Because of Physical or Mental Disability § 268.707 Program accessibility: Existing facilities. (a) General. The Board shall operate each program or activity so that the program or activity... can demonstrate would result in a fundamental alteration in the nature of a program or activity or in...

12 CFR 268.707 - Program accessibility: Existing facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs and Activities Because of Physical or Mental Disability § 268.707 Program accessibility: Existing facilities. (a) General. The Board shall operate each program or activity so that the program or activity... can demonstrate would result in a fundamental alteration in the nature of a program or activity or in...

16 CFR 6.150 - Program accessibility: Existing facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF PRACTICE ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES.... The Commission shall operate each program or activity so that the program or activity, when viewed in... demonstrate would result in a fundamental alteration in the nature of a program or activity or in undue...

The Afrocentric Paradigm in Health-Related Physical Activity.

ERIC Educational Resources Information Center

Pittman, Beverly D.

2003-01-01

Examines the potential role of culture in health-related physical activity participation, discussing kinesiology and reporting results from a health-related physical activity study of women, some of whom had taken a culturally designed aerobics class. Participants demonstrated the positive impact of culture on physical activity participation.…

Cosmogenically-produced isotopes in natural and enriched high-purity germanium detectors for the MAJORANA DEMONSTRATOR

NASA Astrophysics Data System (ADS)

Gilliss, Thomas; MAJORANA DEMONSTRATOR Collaboration

2017-01-01

The MAJORANA DEMONSTRATOR advances toward measurements of the neutrinoless double-beta decay of 76Ge. Detectors employed in the DEMONSTRATOR are subject to cosmogenic spallation during production and processing, resulting in activation of certain long-lived radioisotopes. Activation of these cosmogenic isotopes is mitigated by shielded storage of detectors and through underground operation of the DEMONSTRATOR at the 4850 ft level of the Sanford Underground Research Facility. In this work, we explore the appearance and reduction of cosmogenic contributions to the DEMONSTRATOR background spectrum. This work is supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, the Particle Astrophysics and Nuclear Physics Programs of the National Science Foundation, and the Sanford Underground Research Facility.

Development through Dissent: Campus Activism as Civic Learning

ERIC Educational Resources Information Center

Biddix, J. Patrick

2014-01-01

This chapter traces two decades of published research on learning outcomes related to campus activism and reports results from a speculative study considering civic outcomes from participation in campus political and war demonstrations.

Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin.

PubMed

Xu, Wei; Hong, Seok Jong; Zeitchek, Michael; Cooper, Garry; Jia, Shengxian; Xie, Ping; Qureshi, Hannan A; Zhong, Aimei; Porterfield, Marshall D; Galiano, Robert D; Surmeier, D James; Mustoe, Thomas A

2015-03-01

Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from wounds decreases scar formation. We hypothesized that hydration status changes sodium homeostasis and induces sodium flux in keratinocytes, which result in activation of pathways responsible for keratinocyte-fibroblast signaling and ultimately lead to activation of fibroblasts. Here, we demonstrate that perturbations in epithelial barrier function lead to increased sodium flux in keratinocytes. We identified that sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs) and causes increased secretion of proinflammatory cytokines, which activate fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway. Similar changes in signal transduction and sodium flux occur by increased sodium concentration, which simulates reduced hydration, in the media in epithelial cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin synthesis, or PGE2 receptors all reduce markers of fibroblast activation and collagen synthesis. In addition, employing a validated in vivo excessive scar model in the rabbit ear, we demonstrate that utilization of either an ENaC blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other experiments demonstrate that the activation of COX-2 in response to increased sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis.

Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

NASA Astrophysics Data System (ADS)

Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

2016-08-01

Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

Survey of Active Vibration Isolation Systems for Microgravity Applications

NASA Technical Reports Server (NTRS)

Grodsinsky, Carlos M.; Whorton, Mark S.

2000-01-01

In view of the utility of space vehicles as orbiting science laboratories, the need for vibration isolation systems for acceleration-sensitive experiments has gained increasing visibility. To date, three active microgravity vibration isolation systems have successfully been demonstrated in flight. A tutorial discussion of the microgravity vibration isolation problem, including a description of the acceleration environment of the International Space Station and attenuation requirements, as well as a comparison or the dynamics of passive isolation, active rack-level isolation, and active payload-level isolation is provided. The flight test results of the three demonstrated systems: suppression of transient accelerations by levitation, the microgravity vibration isolation mount, and the active rack isolation system are surveyed.

Inhibitory effects of methamphetamine on mast cell activation and cytokine/chemokine production stimulated by lipopolysaccharide in C57BL/6J mice.

PubMed

Xue, Li; Geng, Yan; Li, Ming; Jin, Yao-Feng; Ren, Hui-Xun; Li, Xia; Wu, Feng; Wang, Biao; Cheng, Wei-Ying; Chen, Teng; Chen, Yan-Jiong

2018-04-01

Previous studies have demonstrated that methamphetamine (MA) influences host immunity; however, the effect of MA on lipopolysaccharide (LPS)-induced immune responses remains unknown. Mast cells (MCs) are considered to serve an important role in the innate and acquired immune response, but it remains unknown whether MA modulates MC activation and LPS-stimulated cytokine production. The present study aimed to investigate the effect of MA on LPS-induced MC activation and the production of MC-derived cytokines in mice. Markers for MC activation, including cluster of differentiation 117 and the type I high affinity immunoglobulin E receptor, were assessed in mouse intestines. Levels of MC-derived cytokines in the lungs and thymus were also examined. The results demonstrated that cytokines were produced in the bone marrow-derived mast cells (BMMCs) of mice. The present study demonstrated that MA suppressed the LPS-mediated MC activation in mouse intestines. MA also altered the release of MC cytokines in the lung and thymus following LPS stimulation. In addition, LPS-stimulated cytokines were decreased in the BMMCs of mice following treatment with MA. The present study demonstrated that MA may regulate LPS-stimulated MC activation and cytokine production.

An aeroelastician's perspective of wind tunnel and flight experiences with active control of structural response and stability

NASA Technical Reports Server (NTRS)

Hanson, P. W.

1984-01-01

Active controls technology is assessed based on a review of most of the wind-tunnel and flight tests and actual applications of active control concepts since the late sixties. The distinction is made between so-called ""rigid-body'' active control functions and those that involve significant modification of structural elastic response or stability. Both areas are reviewed although the focus is on the latter area. The basic goals and major results of the various studies or applications are summarized, and the anticipated use of active controls on current and near-future research and demonstration aircraft is discussed. Some of the ""holes'' remaining in the feasbility/benefits demonstration of active controls technology are examined.

1 CFR 457.150 - Program accessibility: Existing facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE NATIONAL CAPITAL PLANNING COMMISSION § 457... activity so that the program or activity, when viewed in its entirety, is readily accessible to and usable... can demonstrate would result in a fundamental alteration in the nature of a program or activity or in...

Cytochemical demonstration of extraperoxisomal catalase. I. Sheep liver.

PubMed

Roels, F

1976-06-01

In sheep hepatocytes catalase activity was demonstrated both within peroxisomes and within the cytosol. In the cytosol the catalase reaction product is contiguous to the plasma membrane and surrounds the nuclei, rough endoplasmic reticulum, cisternae, mitochondria and Golgi apparatus. This is the first cytochemical demonstration of guine extraperoxisomal catalase. No catalase reaction product was seen in the cytosol of nonparenchymal cells. To demonstrate catalase, both glutaraldehyde and formaldehyde fixation were used, followed by a diaminobenzidine technique modified from Novikoff and Goldfischer. Control reactions were performed to distinguish catalase reaction product from adsorption of oxidized diaminobenzidine and from precipitate due to oxidase-, peroxidase- or heat-stable peroxidatic activities. The results were evaluated in the light and electron microscopes.

NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1

PubMed Central

Baig, Mirza Saqib; Zaichick, Sofia V.; Mao, Mao; de Abreu, Andre L.; Bakhshi, Farnaz R.; Hart, Peter C.; Saqib, Uzma; Deng, Jing; Chatterjee, Saurabh; Block, Michelle L.; Vogel, Stephen M.; Malik, Asrar B.; Consolaro, Marcia E.L.; Christman, John W.; Minshall, Richard D.

2015-01-01

The NF-κB pathway is central to the regulation of inflammation. Here, we demonstrate that the low-output nitric oxide (NO) synthase 1 (NOS1 or nNOS) plays a critical role in the inflammatory response by promoting the activity of NF-κB. Specifically, NOS1-derived NO production in macrophages leads to proteolysis of suppressor of cytokine signaling 1 (SOCS1), alleviating its repression of NF-κB transcriptional activity. As a result, NOS1−/− mice demonstrate reduced cytokine production, lung injury, and mortality when subjected to two different models of sepsis. Isolated NOS1−/− macrophages demonstrate similar defects in proinflammatory transcription on challenge with Gram-negative bacterial LPS. Consistently, we found that activated NOS1−/− macrophages contain increased SOCS1 protein and decreased levels of p65 protein compared with wild-type cells. NOS1-dependent S-nitrosation of SOCS1 impairs its binding to p65 and targets SOCS1 for proteolysis. Treatment of NOS1−/− cells with exogenous NO rescues both SOCS1 degradation and stabilization of p65 protein. Point mutation analysis demonstrated that both Cys147 and Cys179 on SOCS1 are required for its NO-dependent degradation. These findings demonstrate a fundamental role for NOS1-derived NO in regulating TLR4-mediated inflammatory gene transcription, as well as the intensity and duration of the resulting host immune response. PMID:26324446

[Ecological demonstration activity and eco-civilization construction mode: review and prospects].

PubMed

Mao, Hui-ping; He, Xuan; He, Jia; Niu, Dong-jie; Bao, Cun-kuan

2013-04-01

Ecological civilization is to normalize human development behaviors to harmonize the relationships between social and ecological development and eco-environment protection. In this paper, a comparative analysis was made on the ecological demonstration activities of ecological demonstration areas led by the Ministry of Environmental Protection, exemplar cities of national environmental protection, and ecological provinces, cities, and counties. It was considered that all the ecological demonstration activities had the problems of lacking pertinence of construction goals, disordered construction subjects, inefficient construction processes, and lacking continuous incentive mechanisms of assessment. In the meantime, through the analysis of the connotations of eco-civilization, the relationships between eco-civilization and eco-demonstration constructions were approached, and the eco-civilization construction mode was put forward in terms of construction goal, construction subject, and construction processes and assessment. The construction mode included the construction goal based on regional characteristics; the synergistic cooperation of construction subjects, the expanding ways of public participation, and the establishment of evaluation system for comprehensively measuring the 'actions and results'.

Design and implementation of robust decentralized control laws for the ACES structure at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Collins, Emmanuel G., Jr.; Phillips, Douglas J.; Hyland, David C.

1990-01-01

Many large space system concepts will require active vibration control to satisfy critical performance requirements such as line-of-sight accuracy. In order for these concepts to become operational it is imperative that the benefits of active vibration control be practically demonstrated in ground based experiments. The results of the experiment successfully demonstrate active vibration control for a flexible structure. The testbed is the Active Control Technique Evaluation for Spacecraft (ACES) structure at NASA Marshall Space Flight Center. The ACES structure is dynamically traceable to future space systems and especially allows the study of line-of-sight control issues.

Development of a laboratory demonstration model active cleaning device

NASA Technical Reports Server (NTRS)

Shannon, R. L.; Gillette, R. B.

1975-01-01

A laboratory demonstration model of a device for removing contaminant films from optical surfaces in space was developed. The development of a plasma tube, which would produce the desired cleaning effects under high vacuum conditions, represented the major problem in the program. This plasma tube development is discussed, and the resulting laboratory demonstration-model device is described.

Activating Event Knowledge

ERIC Educational Resources Information Center

Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

2009-01-01

An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

Specificity of sexual arousal for sexual activities in men and women with conventional and masochistic sexual interests.

PubMed

Chivers, Meredith L; Roy, Carolyn; Grimbos, Teresa; Cantor, James M; Seto, Michael C

2014-07-01

Prior studies consistently report that men's genital responses correspond to their sexual activity interests (consenting vs. coercive sex) whereas women's responses do not. For women, however, these results may be confounded by the sexual activities studied and lack of suitable controls. We examined the subjective and genital arousal responses of men and women with conventional (22 men and 15 women) or masochistic sexual interests (16 men and 17 women) to narratives describing conventional sex or masochistic sex. The aims of the studies were twofold: (1) to examine whether gender differences in the specificity of sexual arousal previously observed for gender also exist for sexual activity interests; and (2) to examine whether men and women with masochistic sexual interests demonstrate specificity of sexual response for their preferred sexual activities. Surprisingly, the pattern of results was very similar for men and women. Both men and women with conventional sexual interests (WCI) reported more sexual arousal, and responded more genitally, to conventional than to masochistic sex, demonstrating specificity of sexual arousal for their preferred sexual activities. Despite showing specificity for conventional sexual activities, the genital responses of WCI were still gender nonspecific. In contrast, women and men with masochistic sexual interests demonstrated nonspecific subjective and genital responses to conventional and masochistic sex. Indices of genital and subjective sexual arousal to masochistic versus conventional stimuli were positively and significantly correlated with self-reported thoughts, fantasies, interests, and behaviors involving masochism. The results suggest that gender similarities in the specificity of sexual arousal for sexual activity exist despite consistent gender differences in the specificity of sexual arousal for gender.

In vitro Reactivity to Implant Metals Demonstrates a Person Dependent Association with both T-Cell and B-Cell Activation

PubMed Central

Hallab, Nadim James; Caicedo, Marco; Epstein, Rachael; McAllister, Kyron; Jacobs, Joshua J

2009-01-01

Hypersensitivity to metallic implants remains relatively unpredictable and poorly understood. We initially hypothesized that metal-induced lymphocyte proliferation responses to soluble metal challenge (ions) are mediated exclusively by early T-cell activation (not B-cells), typical of a Delayed-Type-Hypersensitivity response. We tested this by comparing proliferation (6-days) of primary lymphocytes with early T-cell and B-cell activation (48-hours) in three groups of subjects likely to demonstrate elevated metal-reactivity: Group 1(n=12) history of metal-sensitivity with no implant; Group 2a(n=6) well performing metal-on-metal THRs, and Group 2b(n=20) subjects with poorly performing metal-on-polymer total joint arthroplasties (TJA). Group 1 showed 100%(12/12) metal reactivity (Stimulation Index>2) to Ni. Group 2a&2b were 83%(5/6) and 75%(15/22) metal reactive (to Co, Cr or Ni) respectively. Of the n=32 metal reactive subjects to Co, Cr or Ni (SI>2), n=22/32 demonstrated >2-fold elevations in % of T-cell or B-cell activation (CD25+,CD69+) to metal challenge compared to untreated control. 18/22 metal-activated subjects demonstrated an exclusively T-cell or B-cell activation response to metal challenge, where 6/18 demonstrated exclusively B-cell activation and 12/18 demonstrated a T-cell only response, as measured by surface activation markers CD25+ and CD69+. However, there was no direct correlation (R2<0.1) between lymphocyte proliferation and % T-cell or B-cell activation (CD25+:CD69+). Proliferation assays (LTT) showed greater ability to detect metal reactivity than did subject-dependent results of flow-cytometry analysis of T-cell or B-cell activation. The high incidence of lymphocyte reactivity and activation, indicate that more complex than initially hypothesized immune responses may contribute to the etiology of debris induced osteolysis in metal-sensitive individuals. PMID:19235773

T Cell Activation Thresholds are Affected by Gravitational

NASA Technical Reports Server (NTRS)

Adams, Charley; Gonzalez, M.; Nelman-Gonzalez, M.

1999-01-01

T cells stimulated in space flight by various mitogenic signals show a dramatic reduction in proliferation and expression of early activation markers. Similar results are also obtained in a ground based model of microgravity, clinorotation, which provides a vector-averaged reduction of the apparent gravity on cells without significant shear force. Here we demonstrate that T cell inhibition is due to an increase in the required threshold for activation. Dose response curves indicate that cells activated during clinorotation require higher stimulation to achieve the same level of activation, as measured by CD69 expression. Interleukin 2 receptor expression, and DNA synthesis. The amount of stimulation necessary for 50% activation is 5 fold in the clinostat relative to static. Correlation of TCR internalization with activation also exhibit a dramatic right shift in clinorotation, demonstrating unequivocally that signal transduction mechanism independent of TCR triggering account for the increased activation threshold. Previous results from space flight experiments are consistent with the dose response curves obtained for clinorotation. Activation thresholds are important aspects of T cell memory, autoimmunity and tolerance Clinorotation is a useful, noninvasive tool for the study of cellular and biochemical event regulating T cell activation threshold and the effects of gravitation forces on these systems.

Cysteine Cathepsins in Human Carious Dentin

PubMed Central

Nascimento, F.D.; Minciotti, C.L.; Geraldeli, S.; Carrilho, M.R.; Pashley, D.H.; Tay, F.R.; Nader, H.B.; Salo, T.; Tjäderhane, L.; Tersariol, I.L.S.

2011-01-01

Matrix metalloproteinases (MMPs) are important in dentinal caries, and analysis of recent data demonstrates the presence of other collagen-degrading enzymes, cysteine cathepsins, in human dentin. This study aimed to examine the presence, source, and activity of cysteine cathepsins in human caries. Cathepsin B was detected with immunostaining. Saliva and dentin cysteine cathepsin and MMP activities on caries lesions were analyzed spectrofluorometrically. Immunostaining demonstrated stronger cathepsins B in carious than in healthy dentin. In carious dentin, cysteine cathepsin activity increased with increasing depth and age in chronic lesions, but decreased with age in active lesions. MMP activity decreased with age in both active and chronic lesions. Salivary MMP activities were higher in patients with active than chronic lesions and with increasing lesion depth, while cysteine cathepsin activities showed no differences. The results indicate that, along with MMPs, cysteine cathepsins are important, especially in active and deep caries. PMID:21248362

Cancer-preventive activities of tocopherols and tocotrienols.

PubMed

Ju, Jihyeung; Picinich, Sonia C; Yang, Zhihong; Zhao, Yang; Suh, Nanjoo; Kong, Ah-Ng; Yang, Chung S

2010-04-01

The cancer-preventive activity of vitamin E has been studied. Whereas some epidemiological studies have suggested a protective effect of vitamin E against cancer formation, many large-scale intervention studies with alpha-tocopherol (usually large doses) have not demonstrated a cancer-preventive effect. Studies on alpha-tocopherol in animal models also have not demonstrated robust cancer prevention effects. One possible explanation for the lack of demonstrable cancer-preventive effects is that high doses of alpha-tocopherol decrease the blood and tissue levels of delta-tocopherols. It has been suggested that gamma-tocopherol, due to its strong anti-inflammatory and other activities, may be the more effective form of vitamin E in cancer prevention. Our recent results have demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon, prostate, mammary and lung tumorigenesis in animal models, suggesting that this mixture may have a high potential for applications in the prevention of human cancer. In this review, we discuss biochemical properties of tocopherols, results of possible cancer-preventive effects in humans and animal models and possible mechanisms involved in the inhibition of carcinogenesis. Based on this information, we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research.

Biosurfactant Production by Bacillus salmalaya for Lubricating Oil Solubilization and Biodegradation.

PubMed

Dadrasnia, Arezoo; Ismail, Salmah

2015-08-19

This study investigated the capability of a biosurfactant produced by a novel strain of Bacillus salmalaya to enhance the biodegradation rates and bioavailability of organic contaminants. The biosurfactant produced by cultured strain 139SI showed high physicochemical properties and surface activity in the selected medium. The biosurfactant exhibited a high emulsification index and a positive result in the drop collapse test, with the results demonstrating the wetting activity of the biosurfactant and its potential to produce surface-active molecules. Strain 139SI can significantly reduce the surface tension (ST) from 70.5 to 27 mN/m, with a critical micelle concentration of 0.4%. Moreover, lubricating oil at 2% (v/v) was degraded on Day 20 (71.5). Furthermore, the biosurfactant demonstrated high stability at different ranges of salinity, pH, and temperature. Overall, the results indicated the potential use of B. salmalaya 139SI in environmental remediation processes.

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

PubMed Central

Rodríguez-Beltrán, Jerónimo; Cabot, Gabriel; Valencia, Estela Ynés; Costas, Coloma; Bou, German; Oliver, Antonio

2015-01-01

The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes. PMID:25801561

N-acetylcysteine selectively antagonizes the activity of imipenem in Pseudomonas aeruginosa by an OprD-mediated mechanism.

PubMed

Rodríguez-Beltrán, Jerónimo; Cabot, Gabriel; Valencia, Estela Ynés; Costas, Coloma; Bou, German; Oliver, Antonio; Blázquez, Jesús

2015-01-01

The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Eliminating the Simon Effect by Instruction

ERIC Educational Resources Information Center

Theeuwes, Marijke; Liefooghe, Baptist; De Houwer, Jan

2014-01-01

A growing body of research demonstrates that instructions can elicit automatic response activations. The results of the present study indicate that instruction-based response activations can also counteract automatic response activations based on long-term associations. To this end, we focused on the Simon effect, which is the observation that…

Actively Controlling Buffet-Induced Excitations

NASA Technical Reports Server (NTRS)

Moses, Robert W.; Pototzky, Anthony S.; Henderson, Douglas A.; Galea, Stephen C.; Manokaran, Donald S.; Zimcik, David G.; Wickramasinghe, Viresh; Pitt, Dale M.; Gamble, Michael A.

2005-01-01

High performance aircraft, especially those with twin vertical tails, encounter unsteady buffet loads when flying at high angles of attack. These loads result in significant random stresses, which may cause fatigue damage leading to restricted capabilities and availability of the aircraft. An international collaborative research activity among Australia, Canada and the United States, conducted under the auspices of The Technical Cooperation Program (TTCP) contributed resources toward a program that coalesced a broad range of technical knowledge and expertise into a single investigation to demonstrate the enhanced performance and capability of the advanced active BLA control system in preparation for a flight test demonstration. The research team investigated the use of active structural control to alleviate the damaging structural response to these loads by applying advanced directional piezoelectric actuators, the aircraft rudder, switch mode amplifiers, and advanced control strategies on an F/A-18 aircraft empennage. Some results of the full-scale investigation are presented herein.

Synthesis and cytotoxic evaluation of novel symmetrical taspine derivatives as anticancer agents.

PubMed

Zhang, Jie; Zhang, Yanmin; Pan, Xiaoyan; Wang, Sicen; He, Langchon

2011-07-01

It has been demonstrated that taspine derivatives act as anticancer agents, thus we designed and synthesized a novel class of symmetrical biphenyl derivatives. We evaluated the cytotoxicity and antitumor activity of biphenyls against five human tumor and normal cell lines. The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control. Compounds (11) and (12) demonstrated the most potent cytotoxic activity with IC₅₀ values between 19.41 µM and 29.27 µM. The potent antiproliferative capabilities of these compounds against ECV304 human transformed endothelial cells indicated that these biphenyls could potentially serve as antiangiogenic agents. We also reviewed the relationship between structure and activity based on the experimental results. Our findings provide a good starting point for further development of symmetrical biphenyl derivatives as potential novel anticancer agents.

Taming active turbulence with patterned soft interfaces.

PubMed

Guillamat, P; Ignés-Mullol, J; Sagués, F

2017-09-15

Active matter embraces systems that self-organize at different length and time scales, often exhibiting turbulent flows apparently deprived of spatiotemporal coherence. Here, we use a layer of a tubulin-based active gel to demonstrate that the geometry of active flows is determined by a single length scale, which we reveal in the exponential distribution of vortex sizes of active turbulence. Our experiments demonstrate that the same length scale reemerges as a cutoff for a scale-free power law distribution of swirling laminar flows when the material evolves in contact with a lattice of circular domains. The observed prevalence of this active length scale can be understood by considering the role of the topological defects that form during the spontaneous folding of microtubule bundles. These results demonstrate an unexpected strategy for active systems to adapt to external stimuli, and provide with a handle to probe the existence of intrinsic length and time scales.Active nematics consist of self-driven components that develop orientational order and turbulent flow. Here Guillamat et al. investigate an active nematic constrained in a quasi-2D geometrical setup and show that there exists an intrinsic length scale that determines the geometry in all forcing regimes.

Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

PubMed

Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

2008-12-01

Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports.

PubMed

Inui, Toshio; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Sakamoto, Norihiro; Mette, Martin

2015-08-01

Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades. Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy. Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects. We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A Survey of Active Vibration Isolation Systems for Microgravity Applications

NASA Technical Reports Server (NTRS)

Grodsinsky, Carlos M.; Whorton, Mark S.

2000-01-01

In view of the utility of space vehicles as orbiting science laboratories, the need for vibration isolation systems for acceleration sensitive experiments has gained increasing visibility. To date, three active microgravity vibration isolation systems have successfully been demonstrated in flight. This paper provides a tutorial discussion of the microgravity vibration isolation problem including a description of the acceleration environment of the International Space Station and attenuation requirements as well as a comparison of the dynamics of passive isolation, active rack-level isolation, and active payload-level isolation. This paper also surveys the flight test results of the three demonstrated systems: Suppression of Transient Accelerations By Levitation (STABLE); the Microgravity Vibration Isolation Mount (MIM); and the Active Rack Isolation System (ARIS).

Evaluating a Model of Youth Physical Activity

PubMed Central

Heitzler, Carrie D.; Lytle, Leslie A.; Erickson, Darin J.; Barr-Anderson, Daheia; Sirard, John R.; Story, Mary

2011-01-01

Objective To explore the relationship between social influences, self-efficacy, enjoyment, and barriers and physical activity. Methods Structural equation modeling examined relationships between parent and peer support, parent physical activity, individual perceptions, and objectively measured physical activity using accelerometers among a sample of youth aged 10–17 years (N=720). Results Peer support, parent physical activity, and perceived barriers were directly related to youth activity. The proposed model accounted for 14.7% of the variance in physical activity. Conclusions The results demonstrate a need to further explore additional individual, social, and environmental factors that may influence youth’s regular participation in physical activity. PMID:20524889

Brain activity in valuation regions while thinking about the future predicts individual discount rates.

PubMed

Cooper, Nicole; Kable, Joseph W; Kim, B Kyu; Zauberman, Gal

2013-08-07

People vary widely in how much they discount delayed rewards, yet little is known about the sources of these differences. Here we demonstrate that neural activity in ventromedial prefrontal cortex (VMPFC) and ventral striatum (VS) when human subjects are asked to merely think about the future--specifically, to judge the subjective length of future time intervals--predicts delay discounting. High discounters showed lower activity for longer time delays, while low discounters showed the opposite pattern. Our results demonstrate that the correlation between VMPFC and VS activity and discounting occurs even in the absence of choices about future rewards, and does not depend on a person explicitly evaluating future outcomes or judging their self-relevance. This suggests a link between discounting and basic processes involved in thinking about the future, such as temporal perception. Our results also suggest that reducing impatience requires not suppression of VMPFC and VS activity altogether, but rather modulation of how these regions respond to the present versus the future.

Brain Activity in Valuation Regions while Thinking about the Future Predicts Individual Discount Rates

PubMed Central

Cooper, Nicole; Kim, B. Kyu; Zauberman, Gal

2013-01-01

People vary widely in how much they discount delayed rewards, yet little is known about the sources of these differences. Here we demonstrate that neural activity in ventromedial prefrontal cortex (VMPFC) and ventral striatum (VS) when human subjects are asked to merely think about the future—specifically, to judge the subjective length of future time intervals—predicts delay discounting. High discounters showed lower activity for longer time delays, while low discounters showed the opposite pattern. Our results demonstrate that the correlation between VMPFC and VS activity and discounting occurs even in the absence of choices about future rewards, and does not depend on a person explicitly evaluating future outcomes or judging their self-relevance. This suggests a link between discounting and basic processes involved in thinking about the future, such as temporal perception. Our results also suggest that reducing impatience requires not suppression of VMPFC and VS activity altogether, but rather modulation of how these regions respond to the present versus the future. PMID:23926268

Comparing responses to horticultural-based and traditional activities in dementia care programs.

PubMed

Jarrott, Shannon E; Gigliotti, Christina M

2010-12-01

Engaging persons with dementia in meaningful activities supports well-being; however, care staff are challenged to implement age- and ability-appropriate activities in a group setting. We compared a randomly assigned treatment group, who received horticultural therapy-based (HT-based) programming to a comparison group, who engaged in traditional activities (TA) programming, on engagement and affect. Horticultural therapy-based programming was implemented twice weekly at 4 treatment sites for 6 weeks, while regular TA were observed at comparison sites. Results revealed no differences between groups on affective domains. Levels of adaptive behavior differed between the groups, with the treatment group demonstrating higher levels of active, passive, and other engagement and the comparison group demonstrating higher levels of self-engagement. Our results highlight the value of HT-based programs and the importance of simultaneously capturing participants' affective and behavioral responses. Theoretical and practical considerations about the facilitation of and context in which the programming occurs are discussed.

Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality.

PubMed

Donley, David W; Olson, Andrew R; Raisbeck, Merl F; Fox, Jonathan H; Gigley, Jason P

2016-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals. T. gondii infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and T. gondii infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early-advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how T. gondii infection may interact with pathways mediating neurodegeneration in HD.

Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality

PubMed Central

Donley, David W.; Olson, Andrew R.; Raisbeck, Merl F.; Fox, Jonathan H.; Gigley, Jason P.

2016-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals. T. gondii infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and T. gondii infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early–advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how T. gondii infection may interact with pathways mediating neurodegeneration in HD. PMID:27611938

Preliminary Results form the Japanese Total Lightning Network

NASA Astrophysics Data System (ADS)

Hobara, Y.; Ishii, H.; Kumagai, Y.; Liu, C.; Heckman, S.; Price, C. G.; Williams, E. R.

2015-12-01

We report on the initial observational results from the first Japanese Total Lightning Detection Network (JTLN) in relation to severe weather phenomena. The University of Electro-Communications (UEC) has deployed the Earth Networks (EN) Total Lightning System over Japan to carry out research on the relationship between thunderstorm activity and severe weather phenomena since 2013. In this paper we first demonstrate the current status of our new network followed by the initial scientific results. The lightning jump algorithm was applied to our total lightning data to study the relationship between total lighting activity and hazardous weather events such as gust fronts and tornadoes over land reported by the JMA (Japanese Meteorological Agency) in 2014. As a result, a clear increase in total lighting flash rate as well as lightning jumps are observed prior to most hazardous weather events (~20 min) indicating potential usefulness for early warning in Japan. Furthermore we are going to demonstrate the relationship of total lightning activities with meteorological radar data focusing particularly on Japanese Tornadic storms.

Results of the joint utilization of laser integrated experiments flown on payload GAS-449 aboard Columbia mission 61-C

NASA Technical Reports Server (NTRS)

Muckerheide, M. C.

1987-01-01

The high peak power neodymium YAG laser and the HeNe laser aboard GAS-449 have demonstrated the survivability of the devices in the micro-gravity, cosmic radiation, thermal, and shock environment of space. Some pharmaceuticals and other materials flown in both the active and passive status have demonstrated reduction in volume and unusual spectroscopic changes. X-ray detectors have shown cosmic particle hits with accompanying destruction at their interaction points. Some scattering in the plates is in evidence. Some results of both active and passive experiments on board the GAS-449 payload are evaluated.

Altered prefrontal correlates of monetary anticipation and outcome in chronic pain.

PubMed

Martucci, Katherine T; Borg, Nicholas; MacNiven, Kelly H; Knutson, Brian; Mackey, Sean C

2018-04-04

Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation-possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain.

Sulforaphane inhibits endothelial protein C receptor shedding in vitro and in vivo.

PubMed

Ku, Sae-Kwang; Han, Min-Su; Bae, Jong-Sup

2014-10-01

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Increasing evidence has demonstrated that beyond its role in the activation of protein C, endothelial cell protein C receptor (EPCR) is also involved in vascular inflammation. EPCR activity is markedly changed by ectodomain cleavage and its release as the soluble EPCR. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). However, little is known about the effects of SFN on EPCR shedding. Our results demonstrated that SFN induced potent inhibition of phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α-, interleukin (IL)-1β, and cecal ligation and puncture (CLP)-induced EPCR shedding. SFN also inhibited the expression and activity of PMA-induced TACE in endothelial cells. In addition, treatment with SFN resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results demonstrate the potential of SFN as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding. Copyright © 2014 Elsevier Inc. All rights reserved.

Activation and function of mitochondrial uncoupling protein in plants.

PubMed

Smith, Anna M O; Ratcliffe, R George; Sweetlove, Lee J

2004-12-10

Plant mitochondrial uncoupling protein (UCP) is activated by superoxide suggesting that it may function to minimize mitochondrial reactive oxygen species (ROS) formation. However, the precise mechanism of superoxide activation and the exact function of UCP in plants are not known. We demonstrate that 4-hydroxy-2-nonenal (HNE), a product of lipid peroxidation, and a structurally related compound, trans-retinal, stimulate a proton conductance in potato mitochondria that is inhibitable by GTP (a characteristic of UCP). Proof that the effects of HNE and trans-retinal are mediated by UCP is provided by examination of proton conductance in transgenic plants overexpressing UCP. These experiments demonstrate that the mechanism of activation of UCP is conserved between animals and plants and imply a conservation of function. Mitochondria from transgenic plants overexpressing UCP were further studied to provide insight into function. Experimental conditions were designed to mimic a bioenergetic state that might be found in vivo (mitochondria were supplied with pyruvate as well as tricarboxylic cycle acids at in vivo cytosolic concentrations and an exogenous ATP sink was established). Under such conditions, an increase in UCP protein content resulted in a modest but significant decrease in the rate of superoxide production. In addition, 13C-labeling experiments revealed an increase in the conversion of pyruvate to citrate as a result of increased UCP protein content. These results demonstrate that under simulated in vivo conditions, UCP is active and suggest that UCP may influence not only mitochondrial ROS production but also tricarboxylic acid cycle flux.

Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

PubMed

Soeiro-De-Souza, Marcio Gerhardt; Bio, Danielle Soares; David, Denise Petresco; Missio, Giovani; Lima, Bruno; Fernandes, Fernando; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

2013-09-01

Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender‑specific effects of the COMT genotype on cognition in healthy young adults. Seventy‑six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

The yeast Hsp70 Ssa1 is a sensor for activation of the heat shock response by thiol-reactive compounds

PubMed Central

Wang, Yanyu; Gibney, Patrick A.; West, James D.; Morano, Kevin A.

2012-01-01

The heat shock transcription factor HSF1 governs the response to heat shock, oxidative stresses, and xenobiotics through unknown mechanisms. We demonstrate that diverse thiol-reactive molecules potently activate budding yeast Hsf1. Hsf1 activation by thiol-reactive compounds is not consistent with the stresses of misfolding of cytoplasmic proteins or cytotoxicity. Instead, we demonstrate that the Hsp70 chaperone Ssa1, which represses Hsf1 in the absence of stress, is hypersensitive to modification by a thiol-reactive probe. Strikingly, mutation of two conserved cysteine residues to serine in Ssa1 rendered cells insensitive to Hsf1 activation and subsequently induced thermotolerance by thiol-reactive compounds, but not by heat shock. Conversely, substitution with the sulfinic acid mimic aspartic acid resulted in constitutive Hsf1 activation. Cysteine 303, located within the nucleotide-binding domain, was found to be modified in vivo by a model organic electrophile, demonstrating that Ssa1 is a direct target for thiol-reactive molecules through adduct formation. These findings demonstrate that Hsp70 is a proximal sensor for Hsf1-mediated cytoprotection and can discriminate between two distinct environmental stressors. PMID:22809627

Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

PubMed

Selheim, F; Holmsen, H; Vassbotn, F S

1999-08-15

We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

Auranofin, as an anti-rheumatic gold compound suppresses LPS-induced homodimerization of TLR4

PubMed Central

Youn, Hyung S.; Lee, Joo Y.; Saitoh, Shin I.; Miyake, Kensuke; Hwang, Daniel H.

2009-01-01

Toll-like receptors (TLRs), which are activated by invading microorganisms or endogenous molecules, evoke immune and inflammatory responses. TLR activation is closely linked to the development of many chronic inflammatory diseases including rheumatoid arthritis. Auranofin, an Au(I) compound, is a well-known and long-used anti-rheumatic drug. However, the mechanism as to how auranofin relieves the symptom of rheumatoid arthritis has not been fully clarified. Our results demonstrated that auranofin suppressed TLR4-mediated activation of transcription factors, NF-κB and IRF3 and expression of COX-2, a pro-inflammatory enzyme. This suppression was well correlated with the inhibitory effect of auranofin on the homodimerization of TLR4 induced by an agonist. Furthermore, auranofin inhibited NF-κ activation induced by MyD88-dependent downstream signaling components of TLR4, MyD88, IKKβ, and p65. IRF3 activation induced by MyD88-independent signaling components, TRIF and TBK1, was also downregulated by auranofin. Our results first demonstrate that auranofin suppresses the multiple steps in TLR4 signaling, especially the homodimerization of TLR4. The results suggest that the suppression of TLR4 activity by auranofin may be the molecular mechanism through which auranofin exerts anti-rheumatic activity. PMID:17034761

MINE WASTE TECHNOLOGY PROGRAM - UNDERGROUND MINE SOURCE CONTROL DEMONSTRATION PROJECT

EPA Science Inventory

This report presents results of the Mine Waste Technology Program Activity III, Project 8, Underground Mine Source Control Demonstration Project implemented and funded by the U. S. Environmental Protection Agency (EPA) and jointly administered by EPA and the U. S. Department of E...

The neuronal correlates of intranasal trigeminal function – An ALE meta-analysis of human functional brain imaging data

PubMed Central

Albrecht, Jessica; Kopietz, Rainer; Frasnelli, Johannes; Wiesmann, Martin; Hummel, Thomas; Lundström, Johan N.

2009-01-01

Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO2), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices – a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO2 stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing. PMID:19913573

Self-consistent simulation of CdTe solar cells with active defects

DOE PAGES

Brinkman, Daniel; Guo, Da; Akis, Richard; ...

2015-07-21

We demonstrate a self-consistent numerical scheme for simulating an electronic device which contains active defects. As a specific case, we consider copper defects in cadmium telluride solar cells. The presence of copper has been shown experimentally to play a crucial role in predicting device performance. The primary source of this copper is migration away from the back contact during annealing, which likely occurs predominantly along grain boundaries. We introduce a mathematical scheme for simulating this effect in 2D and explain the numerical implementation of the system. Lastly, we will give numerical results comparing our results to known 1D simulations tomore » demonstrate the accuracy of the solver and then show results unique to the 2D case.« less

A single amino acid change (Y318F) in the L-arabitol dehydrogenase (LadA) from Aspergillus niger results in a significant increase in affinity for D-sorbitol

PubMed Central

2009-01-01

Background L-arabitol dehydrogenase (LAD) and xylitol dehydrogenase (XDH) are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH). In this study we aimed to identify residues involved in the difference in substrate specificity. Results Phylogenetic analysis demonstrated that LAD, XDH and SDH form 3 distinct groups of the family of dehydrogenases containing an Alcohol dehydrogenase GroES-like domain (pfam08240) and likely have evolved from a common ancestor. Modelling of LadA and XdhA of the saprobic fungus Aspergillus niger on human SDH identified two residues in LadA (M70 and Y318), that may explain the absence of activity on D-sorbitol. While introduction of the mutation M70F in LadA of A. niger resulted in a nearly complete enzyme inactivation, the Y318F resulted in increased activity for L-arabitol and xylitol. Moreover, the affinity for D-sorbitol was increased in this mutant. Conclusion These data demonstrates that Y318 of LadA contributes significantly to the substrate specificity difference between LAD and XDH/SDH. PMID:19674460

Lag threads organize the brain’s intrinsic activity

PubMed Central

Mitra, Anish; Snyder, Abraham Z.; Blazey, Tyler; Raichle, Marcus E.

2015-01-01

It has been widely reported that intrinsic brain activity, in a variety of animals including humans, is spatiotemporally structured. Specifically, propagated slow activity has been repeatedly demonstrated in animals. In human resting-state fMRI, spontaneous activity has been understood predominantly in terms of zero-lag temporal synchrony within widely distributed functional systems (resting-state networks). Here, we use resting-state fMRI from 1,376 normal, young adults to demonstrate that multiple, highly reproducible, temporal sequences of propagated activity, which we term “lag threads,” are present in the brain. Moreover, this propagated activity is largely unidirectional within conventionally understood resting-state networks. Modeling experiments show that resting-state networks naturally emerge as a consequence of shared patterns of propagation. An implication of these results is that common physiologic mechanisms may underlie spontaneous activity as imaged with fMRI in humans and slowly propagated activity as studied in animals. PMID:25825720

Overcoming Resistance to Inhibitors of the Akt Protein Kinase by Modulation of the Pim Kinase Pathway

DTIC Science & Technology

2014-10-01

during hypoxia were biologically meaningful, we investigated the activity of a reporter with multiple HIF binding sites ( HRE ) in front of a luciferase...inhibitors in a dose dependent fashion blocked the activity of the HRE to activate luciferase mRNA and protein production. This result demonstrates that

Anti-Leishmania Activity of Osthole

PubMed Central

Kermani, Elaheh Kordzadeh; Sajjadi, Seyed Ebrahim; Hejazi, Seyed Hossein; Arjmand, Reza; Saberi, Sedigheh; Eskandarian, Abbas Ali

2016-01-01

Background: Treatment of cutaneous leishmaniasis (CL) is occasionally highly resistant to pentavalent antimonials, the gold standard in pharmacotherapy of CL. Since there is no effective vaccine, the discovery of natural antileishmanial products as complementary therapeutic agents could be used to improve the current regimens. Objective: In this study in vitro and in vivo antileishmanial activities of osthole, a natural coumarin known to possess antibacterial and parasiticidal activities are evaluated. Materials and Methods: Leishmania major infected J774.A1 macrophages were treated with increasing concentrations of osthole. CL lesions of BALB/c mice were treated topically with 0.2% osthole. Results: Osthole exhibited dose-dependent leishmanicidal activity against intracellular amastigotes with IC50 value of 14.95 μg/ml. Treatment of CL lesions in BALB/c mice with osthole significantly declined lesion progression compared to untreated mice (P < 0.05), however did not result in recovery. Conclusion: Osthole demonstrated remarkable leishmanicidal activity in vitro. Higher concentrations of osthole may demonstrate the therapeutic property in vivo. SUMMARY In vitro and in vivo antileishmanial activities of osthole, a pernylated coumarin extracted from Prangos asperula Boiss., are studied against Leishmania major. PMID:27114685

Minor modifications to ceritinib enhance anti-tumor activity in EML4-ALK positive cancer.

PubMed

Kang, Chung Hyo; Kim, Eun-Young; Kim, Hyoung Rae; Lee, Chong Ock; Lee, Heung Kyoung; Jeong, Hye Gwang; Choi, Sang Un; Yun, Chang-Soo; Hwang, Jong Yeon; Lee, Joo-Youn; Son, You Hwa; Ahn, Sunjoo; Lee, Byung Hoi; Jung, Heejung; Park, Chi Hoon

2016-05-01

Ceritinib, an ALK inhibitor, was hurriedly approved by the US FDA last year, and demonstrates impressive results in EML4-ALK positive patients. To get a superior ALK inhibitor, we synthesized several ceritinib derivatives with minor modifications to the phenylpiperidine moiety. Biochemical and cellular assays demonstrated the improved activity of KRCA-386 over that of ceritinib. KRCA-386 has superior inhibitory activity against ALK mutants commonly found in crizotinib-resistant patients. Particularly, KRCA-386 has considerably greater activity than ceritinib against the G1202R mutant, one of the most challenging mutations to overcome. The cell cycle analysis indicates that ALK inhibitors induce G1/S arrest, resulting in apoptosis. The in vivo xenograft data also demonstrate that KRCA-386 is significantly better than ceritinib. KRCA-386 dosed at 25 mpk caused 105% tumor growth inhibition (TGI) compared to 72% TGI with ceritinib dosed at 25 mpk. (n = 8, P = 0.010) The kinase profiling assay revealed that several kinases, which are known to be critical for tumor growth, are inhibited by KRCA-386, but not by ceritinib. We anticipate that this characteristic of KRCA-386 enhances its in vivo efficacy. In addition, KRCA-386 shows excellent blood brain barrier penetration compared to ceritinib. These results suggest that KRCA-386 could be useful for crizotinib-resistant patients with brain metastases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

TRL Assessment of Solar Sail Technology Development Following the 20-Meter System Ground Demonstrator Hardware Testing

NASA Technical Reports Server (NTRS)

Young, Roy M.; Montgomery, Edward E.; Montgomery, Sandy; Adams, Charles L.

2007-01-01

The NASA In-Space Propulsion Technology (ISPT) Projects Office has been sponsoring 2 separate, independent system design and development hardware demonstration activities during 2002-2005. ATK Space Systems of Goleta, CA was the prime contractor for one development team and L'Garde, Inc. of Tustin, CA was the prime contractor for the other development team. The goal of these activities was to advance the technology readiness level (TRL) of solar sail propulsion from 3 towards 6 by the year 2006. Component and subsystem fabrication and testing were completed successfully, including the ground deployment of 10-meter and 20-meter ground demonstration hardware systems under vacuum conditions. The deployment and structural testing of the 20-meter solar sail systems was conducted in the 30 meter diameter Space Power Facility thermal-vacuum chamber at NASA Glenn Plum Brook in April though August, 2005. This paper will present the results of the TRL assessment following the solar sail technology development activities associated with the design, development, analysis and testing of the 20-meter system ground demonstrators. Descriptions of the system designs for both the ATK and L'Garde systems will be presented. Changes, additions and evolution of the system designs will be highlighted. A description of the modeling and analyses activities performed by both teams, as well as testing conducted to raise the TRL of solar sail technology will be presented. A summary of the results of model correlation activities will be presented. Finally, technology gaps identified during the assessment and gap closure plans will be presented, along with "lessons learned", subsequent planning activities and validation flight opportunities for solar sail propulsion technology.

[Lotion with hydroquione - tretinoin].

PubMed

Vandael, A; Plaizier-Vercammen, J

2014-09-01

The observed precipitation in a lotion containing 4% of hydrochinon and 0,03% of tretinoine is evaluated. To dissolve both actives, 10% propyleneglycol is used and the alcohol concentration varied. From the results it is demonstrated that at least 54 ml of ethanol 96 degrees is necessary to dissolve both actives. It is also demonstrated that the addition of 0.2% of vitamin C, as antioxidant, is necessary to avoid coloration of the lotion, as a function of time, due to the presence of hydrochinon.

[Evaluating work intensity in major and auxiliary occupations of by-product coke industry].

PubMed

Smagulov, N K; Alpysbayeva, Zh T

2015-01-01

The article covers evaluation of work strain in major and auxiliary occupations of by-product coke industry. The study results conclude that occupational activity of by-product coke industry workers, under exposure to occupational hazards, affects the workers' performance. Major occupations workers demonstrate higher level of functional strain of CNS, poor concentration of attention and lower ability to switch over, decreased general performance, vs. the auxiliary occupations workers who demonstrated increased cardiovascular and neuro-muscular strain due to occupational activity.

ACTIVE SOIL DEPRESSURIZATION (ASD) DEMONSTRATION IN A LARGE BUILDING

EPA Science Inventory

The report gives results of an evaluation of the feasibility of implementing radon resistant construction techniques -- especially active soil depressurization (ASD) -- in new large buildings in Florida. Indoor radon concentrations and radon entry were monitored in a finished bui...

Estrogenic and androgenic activities of TBBA and TBMEPH, metabolites of novel brominated flame retardants, and selected bisphenols, using the XenoScreen XL YES/YAS assay.

PubMed

Fic, Anja; Žegura, Bojana; Gramec, Darja; Mašič, Lucija Peterlin

2014-10-01

The present study investigated and compared the estrogenic and androgenic activities of the three different classes of environmental pollutants and their metabolites using the XenoScreen XL YES/YAS assay, which has advantages compared with the original YES/YAS protocol. Contrary to the parent brominated flame retardants TBB and TBPH, which demonstrated no or very weak (anti)estrogenic or (anti)androgenic activities, their metabolites, TBBA and TBMEPH, exhibited anti-estrogenic (IC50 for TBBA=31.75 μM and IC50 for TBMEPH=0.265 μM) and anti-androgenic (IC50 for TBBA=73.95 μM and IC50 for TBMEPH=2.92 μM) activities. These results reveal that metabolism can enhance the anti-estrogenic and anti-androgenic effects of these two novel brominated flame retardants. Based on the activities of BPAF, BPF, BPA and MBP, we can conclude that the XenoScreen XL YES/YAS assay gives comparable results to the (anti)estrogenic or (anti)androgenic assays that are reported in the literature. For BPA, it was confirmed previously that the metabolite formed after an ipso-reaction (hydroxycumyl alcohol) exhibited higher estrogenic activity compared with the parent BPA, but this was not confirmed for BPAF and BPF ipso-metabolites, which were not active in the XenoScreen YES/YAS assay. Among the substituted BPA analogues, bis-GMA exhibited weak anti-estrogenic activity, BADGE demonstrated weak anti-estrogenic and anti-androgenic activities (IC50=13.73 μM), and the hydrolysed product BADGE·2H2O demonstrated no (anti)estrogenic or (anti)androgenic activities. Copyright © 2014. Published by Elsevier Ltd.

Relationships between changes in Sustained Fronto-Striatal Connectivity and Positive Affect with Antidepressant Treatment in Major Depression

PubMed Central

Heller, Aaron S.; Johnstone, Tom; Light, Sharee; Peterson, Michael J.; Kolden, Gregory G.; Kalin, Ned H.; Davidson, Richard J.

2012-01-01

Objective Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement over time of this network is unknown. Accordingly, we sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. Method Using fMRI, we assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients prior to, and after 2 months of antidepressant treatment. 14 healthy control subjects were scanned over the same interval. Results After 2 months of treatment, self-reported positive affect increased. Those patients demonstrating the largest increases in sustained nucleus accumbens activity over the 2 months were those demonstrating the largest increases in positive affect. In addition, those patients demonstrating the largest increases in sustained fronto-striatal connectivity were also those demonstrating the largest increases in positive affect when controlling for negative affect. Healthy controls showed none of these associations. Conclusions Treatment induced changes in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect. PMID:23223803

Oxone/Fe[superscript 2+] Degradation of Food Dyes: Demonstration of Catalyst-Like Behavior and Kinetic Separation of Color

ERIC Educational Resources Information Center

Nalliah, Ruth E.

2015-01-01

A demonstration of the degradation of food coloring dyes by oxidation via the Fenton reaction can be substituted with a simpler demonstration using the oxidant oxone with iron(II) ions as an activator. The addition of small amounts of solid oxone and iron(II) sulfate to solutions containing mixtures of food coloring results in successive…

Sirt1 restrains lung inflammasome activation in a murine model of sepsis.

PubMed

Gao, Rong; Ma, Zhongsen; Hu, Yuxin; Chen, Jiao; Shetty, Sreerama; Fu, Jian

2015-04-15

Excessive inflammation is a major cause of organ damage during sepsis. The elderly are highly susceptible to sepsis-induced organ injury. Sirt1 expression is reduced during aging. In the present study, we investigated the role of Sirt1, a histone deacetylase, in controlling inflammatory responses in a murine sepsis model induced by cecal ligation and puncture (CLP). We examined lung inflammatory signaling in inducible Sirt1 knockout (Sirt1(-/-)) mice and wild-type littermates (Sirt1(+/+)) after CLP. Our results demonstrated that Sirt1 deficiency led to severe lung inflammatory injury. To further investigate molecular mechanisms of Sirt1 regulation of lung inflammatory responses in sepsis, we conducted a series of experiments to assess lung inflammasome activation after CLP. We detected increased lung inflammatory signaling including NF-κB, signal transducer and activator of transcription 3, and ERK1/2 activation in Sirt1(-/-) mice after CLP. Furthermore, inflammasome activity was increased in Sirt1(-/-) mice after CLP, as demonstrated by increased IL-1β and caspase-7 cleavage and activation. Aggravated inflammasome activation in Sirt1(-/-) mice was associated with the increased production of lung proinflammatory mediators, including ICAM-1 and high-mobility group box 1, and further disruption of tight junctions and adherens junctions, as demonstrated by dramatic reduction of lung claudin-1 and vascular endothelial-cadherin expression, which was associated with the upregulation of matrix metallopeptidase 9 expression. In summary, our results suggest that Sirt1 suppresses acute lung inflammation during sepsis by controlling inflammasome activation pathway. Copyright © 2015 the American Physiological Society.

Hippocampal Context Processing during Acquisition of a Predictive Learning Task Is Associated with Renewal in Extinction Recall.

PubMed

Lissek, Silke; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Tegenthoff, Martin

2016-05-01

Renewal is defined as the recovery of an extinguished response if extinction and retrieval contexts differ. The context dependency of extinction, as demonstrated by renewal, has important implications for extinction-based therapies. Persons showing renewal (REN) exhibit higher hippocampal activation during extinction in associative learning than those without renewal (NOREN), demonstrating hippocampal context processing, and recruit ventromedial pFC in retrieval. Apart from these findings, brain processes generating renewal remain largely unknown. Conceivably, processing differences in task-relevant brain regions that ultimately lead to renewal may occur already in initial acquisition of associations. Therefore, in two fMRI studies, we investigated overall brain activation and hippocampal activation in REN and NOREN during acquisition of an associative learning task in response to presentation of a context alone or combined with a cue. Results of two studies demonstrated significant activation differences between the groups: In Study 1, a support vector machine classifier correctly assigned participants' brain activation patterns to REN and NOREN groups, respectively. In Study 2, REN and NOREN showed similar hippocampal involvement during context-only presentation, suggesting processing of novelty, whereas overall hippocampal activation to the context-cue compound, suggesting compound encoding, was higher in REN. Positive correlations between hippocampal activation and renewal level indicated more prominent hippocampal processing in REN. Results suggest that hippocampal processing of the context-cue compound rather than of context only during initial learning is related to a subsequent renewal effect. Presumably, REN participants use distinct encoding strategies during acquisition of context-related tasks, which reflect in their brain activation patterns and contribute to a renewal effect.

Effects of Lactobacillus plantarum Strain OLL2712 Culture Conditions on the Anti-inflammatory Activities for Murine Immune Cells and Obese and Type 2 Diabetic Mice.

PubMed

Toshimitsu, T; Ozaki, S; Mochizuki, J; Furuichi, K; Asami, Y

2017-04-01

Studies on the health-promoting effects of lactic acid bacteria (LAB) are numerous, but few provide examples of the relationship between LAB function and culture conditions. We verified the effect of differences in culture conditions on Lactobacillus plantarum OLL2712 functionality; this strain exhibits anti-inflammatory activity and preventive effects against metabolic disorders. We measured interleukin-10 (IL-10) and IL-12 production in murine immune cells treated with OLL2712 cells prepared under various culture conditions. The results showed that the IL-10-inducing activities of OLL2712 cells on murine immune cells differed dramatically between OLL2712 groups at different culture phases and using different culture medium components, temperatures, and neutralizing pHs. In particular, exponential-phase cells had much more IL-10-inducing activity than stationary-phase cells. We confirmed that the Toll-like receptor 2 (TLR2) stimulation activity of OLL2712 cells depended on culture conditions in conjunction with IL-10-inducing activity. We also demonstrated functional differences by culture phases in vivo ; OLL2712 cells at exponential phase had more anti-inflammatory activity and anti-metabolic-disorder effects on obese and diabetic mice than those by their stationary-phase counterparts. These results suggest that culture conditions affect the functionality of anti-inflammatory LAB. IMPORTANCE While previous studies demonstrated that culture conditions affected the immunomodulatory properties of lactic acid bacteria (LAB), few have comprehensively investigated the relationship between culture conditions and LAB functionality. In this study, we demonstrated several culture conditions of Lactobacillus plantarum OLL2712 for higher anti-inflammatory activity. We also showed that culture conditions concretely influenced the health-promoting functions of OLL2712 in vivo , particularly against metabolic disorders. Further, we characterized a novel mechanism by which changing LAB culture conditions affected immunomodulatory properties. Our results suggest that culture condition optimization is important for the production of LAB with anti-inflammatory activity. Copyright © 2017 American Society for Microbiology.

Progesterone production requires activation of caspase-3 in preovulatory granulosa cells in a serum starvation model.

PubMed

An, Li-Sha; Yuan, Xiao-Hua; Hu, Ying; Shi, Zi-Yun; Liu, Xiao-Qin; Qin, Li; Wu, Gui-Qing; Han, Wei; Wang, Ya-Qin; Ma, Xu

2012-11-01

Granulosa cells proliferate, differentiate, and undergo apoptosis throughout follicular development. Previous studies have demonstrated that stimulation of progesterone production is accompanied by caspase-3 activation. Moreover, we previously reported that arsenic enhanced caspase-3 activity coupled with progesterone production. Inhibition of caspase-3 activity can significantly inhibit progesterone production induced by arsenic or follicle-stimulating hormone (FSH). Here, we report that serum starvation induces caspase-3 activation coupled with augmentation of progesterone production. Serum starvation also increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition of caspase-3 activity resulted in a decrease in progesterone production. Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted in decreases in P450scc and StAR expression, which may partly contribute to the observed decrease in progesterone production. Our study demonstrates for the first time that progesterone production in preovulatory granulosa cells is required for caspase-3 activation in a serum starvation model. Inhibition of caspase-3 activity can result in decreased expression of the steroidogenic proteins P450scc and StAR. Our work provides further details on the relationship between caspase-3 activation and steroidogenesis and indicates that caspase-3 plays a critical role in progesterone production by granulosa cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of a protein associated with the activity of cytokine-induced killer cells

PubMed Central

Cao, Jingsong; Chen, Cong; Gao, Yongqiang; Hu, Li; Liang, Yu; Xiao, Jianhua

2017-01-01

Cytokine-induced killer cells (CIKs) adoptive immunotherapy for efficient antitumor ability is used clinically, but details regarding the proteins associated with CIK activity remain unclear. In the current study, the cytotoxicity of CIKs on hepatoma was identified to be significantly downregulated by 1.61-fold following gentamincin treatment. Further research revealed that a differentially expressed protein (P43) was significantly downregulated by 1.22-fold using one-dimensional gel electrophoresis analysis. Of these, the P43 was identified as human haptoglobin using liquid chromatography-mass spectrometry. Western blotting demonstrated that the haptoglobin specifically reacted with rabbit anti-human-haptoglobin. Furthermore, western blotting results verified that the haptoglobin was significantly downregulated by 1.17-fold compared with the control group. In addition, the expression of haptoglobin mRNA was significantly downregulated by 1.73-fold following gentamincin treatment. Taken together, the results of the present study demonstrated that the expression of haptoglobin protein was associated with the activity of CIKs, and the results will be beneficial to the further investigation of CIK activity-enhancement mechanism. PMID:29163711

Silybin counteracts lipid excess and oxidative stress in cultured steatotic hepatic cells

PubMed Central

Vecchione, Giulia; Grasselli, Elena; Voci, Adriana; Baldini, Francesca; Grattagliano, Ignazio; Wang, David QH; Portincasa, Piero; Vergani, Laura

2016-01-01

AIM: To investigate in vitro the therapeutic effect and mechanisms of silybin in a cellular model of hepatic steatosis. METHODS: Rat hepatoma FaO cells were loaded with lipids by exposure to 0.75 mmol/L oleate/palmitate for 3 h to mimic liver steatosis. Then, the steatotic cells were incubated for 24 h with different concentrations (25 to 100 μmol/L) of silybin as phytosome complex with vitamin E. The effects of silybin on lipid accumulation and metabolism, and on indices of oxidative stress were evaluated by absorption and fluorescence microscopy, quantitative real-time PCR, Western blot, spectrophotometric and fluorimetric assays. RESULTS: Lipid-loading resulted in intracellular triglyceride (TG) accumulation inside lipid droplets, whose number and size increased. TG accumulation was mediated by increased levels of peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). The lipid imbalance was associated with higher production of reactive oxygen species (ROS) resulting in increased lipid peroxidation, stimulation of catalase activity and activation of nuclear factor kappa-B (NF-κB). Incubation of steatotic cells with silybin 50 μmol/L significantly reduced TG accumulation likely by promoting lipid catabolism and by inhibiting lipogenic pathways, as suggested by the changes in carnitine palmitoyltransferase 1 (CPT-1), PPAR and SREBP-1c levels. The reduction in fat accumulation exerted by silybin in the steatotic cells was associated with the improvement of the oxidative imbalance caused by lipid excess as demonstrated by the reduction in ROS content, lipid peroxidation, catalase activity and NF-κB activation. CONCLUSION: We demonstrated the direct anti-steatotic and anti-oxidant effects of silybin in steatotic cells, thus elucidating at a cellular level the encouraging results demonstrated in clinical and animal studies. PMID:27468193

Antioxidant and hemolytic activities, and effects in rat cutaneous wound healing of a novel polysaccharide from fenugreek (Trigonella foenum-graecum) seeds.

PubMed

Ktari, Naourez; Trabelsi, Imen; Bardaa, Sana; Triki, Mehdi; Bkhairia, Intidhar; Ben Slama-Ben Salem, Rabab; Nasri, Moncef; Ben Salah, Riadh

2017-02-01

The aim of this work was to evaluate the antioxidant and hemolytic activities as well as the in vivo wound healing performance of a novel polysaccharide (FWEP) extracted from fenugreek (Trigonella foenum-graecum) seeds. The antioxidant activity was evaluated in vivo and in vitro using various assays. Results showed that FWEP exhibited strong antioxidant activities but no hemolytic activity was observed towards bovine erythrocytes. The application of FWEP hydrogel on the wound site in a rat model enhanced significantly wound healing activity and accelerated the wound closure after 14days of wound induction. Histological examination also demonstrated fully re-epithelialized wound with a complete epidermal regeneration. Altogether, these evidences demonstrated that FWEP had strong wound healing potential presumably achieved through its antioxidant activities. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of large aperture telescope technology (LATT): test results on a demonstrator bread-board

NASA Astrophysics Data System (ADS)

Briguglio, R.; Xompero, M.; Riccardi, A.; Lisi, F.; Duò, F.; Vettore, C.; Gallieni, D.; Tintori, M.; Lazzarini, P.; Patauner, C.; Biasi, R.; D'Amato, F.; Pucci, M.; Pereira do Carmo, João.

2017-11-01

The concept of a low areal density primary mirror, actively controlled by actuators, has been investigated through a demonstration prototype. A spherical mirror (400 mm diameter, 2.7 Kg mass) has been manufactured and tested in laboratory and on the optical bench, to verify performance, controllability and optical quality. In the present paper we will describe the prototype and the test results.

Introducing practice-based learning and improvement ACGME core competencies into a family medicine residency curriculum.

PubMed

Coleman, Mary Thoesen; Nasraty, Soraya; Ostapchuk, Michael; Wheeler, Stephen; Looney, Stephen; Rhodes, Sandra

2003-05-01

The Accreditation Council for Graduate Medical Education (ACGME) recommends integrating improvement activities into residency training. A curricular change was designed at the Department of Family and Community Medicine, University of Louisville, to address selected ACGME competencies by incorporating practice-based improvement activities into the routine clinical work of family medicine residents. Teams of residents, faculty, and office staff completed clinical improvement projects at three ambulatory care training sites. Residents were given academic credit for participation in team meetings. After 6 months, residents presented results to faculty, medical students, other residents, and staff from all three training sites. Residents, staff, and faculty were recognized for their participation. Resident teams demonstrated ACGME competencies in practice-based improvement: Chart audits indicated improvement in clinical projects; quality improvement tools demonstrated analysis of root causes and understanding of the process; plan-do-study-act cycle worksheets demonstrated the change process. Improvement activities that affect patient care and demonstrate selected ACGME competencies can be successfully incorporated into the daily work of family medicine residents.

Arsenic Removal from Drinking Water by Adsorptive Media USEPA Demonstration Project at Rimrock AZ Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at the Arizona Water Company (AWC) facility in Rimrock, AZ. The objectives of the project were to evaluate: 1) the effectiveness of ...

Arsenic Removal from Drinking Water by Adsorptive Media USEPA Demonstration Project at Bow, NH Final performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the U.S. Environmental Protection Agency (EPA) arsenic removal treatment technology demonstration project at the White Rock Water Company (WRWC) public water system, a small residential drinking w...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA - USEPA DEMONSTRATION PROJECT AT DESERT SANDS MDWCA, NM SIX MONTH EVALUATION

EPA Science Inventory

This report documents the activities performed during, and the results obtained from, the first six months of the arsenic removal treatment technology demonstration project at the Desert Sands Mutual Domestic Water Consumers Association (MDWCA) facility in Anthony, NM. The object...

Active Tuning of Spontaneous Emission by Mie-Resonant Dielectric Metasurfaces.

PubMed

Bohn, Justus; Bucher, Tobias; Chong, Katie E; Komar, Andrei; Choi, Duk-Yong; Neshev, Dragomir N; Kivshar, Yuri S; Pertsch, Thomas; Staude, Isabelle

2018-06-13

Mie-resonant dielectric metasurfaces offer comprehensive opportunities for the manipulation of light fields with high efficiency. Additionally, various strategies for the dynamic tuning of the optical response of such metasurfaces were demonstrated, making them important candidates for reconfigurable optical devices. However, dynamic control of the light-emission properties of active Mie-resonant dielectric metasurfaces by an external control parameter has not been demonstrated so far. Here, we experimentally demonstrate the dynamic tuning of spontaneous emission from a Mie-resonant dielectric metasurface that is situated on a fluorescent substrate and embedded into a liquid crystal cell. By switching the liquid crystal from the nematic state to the isotropic state via control of the cell temperature, we induce a shift of the spectral position of the metasurface resonances. This results in a change of the local photonic density of states, which, in turn, governs the enhancement of spontaneous emission from the substrate. Specifically, we observe spectral tuning of both the electric and magnetic dipole resonances, resulting in a 2-fold increase of the emission intensity at λ ≈ 900 nm. Our results demonstrate a viable strategy to realize flat tunable light sources based on dielectric metasurfaces.

Cleavage of Type I Collagen by Fibroblast Activation Protein-α Enhances Class A Scavenger Receptor Mediated Macrophage Adhesion

PubMed Central

Mazur, Anna; Holthoff, Emily; Vadali, Shanthi; Kelly, Thomas; Post, Steven R.

2016-01-01

Pathophysiological conditions such as fibrosis, inflammation, and tumor progression are associated with modification of the extracellular matrix (ECM). These modifications create ligands that differentially interact with cells to promote responses that drive pathological processes. Within the tumor stroma, fibroblasts are activated and increase the expression of type I collagen. In addition, activated fibroblasts specifically express fibroblast activation protein-α (FAP), a post-prolyl peptidase. Although FAP reportedly cleaves type I collagen and contributes to tumor progression, the specific pathophysiologic role of FAP is not clear. In this study, the possibility that FAP-mediated cleavage of type I collagen modulates macrophage interaction with collagen was examined using macrophage adhesion assays. Our results demonstrate that FAP selectively cleaves type I collagen resulting in increased macrophage adhesion. Increased macrophage adhesion to FAP-cleaved collagen was not affected by inhibiting integrin-mediated interactions, but was abolished in macrophages lacking the class A scavenger receptor (SR-A/CD204). Further, SR-A expressing macrophages localize with activated fibroblasts in breast tumors of MMTV-PyMT mice. Together, these results demonstrate that FAP-cleaved collagen is a substrate for SR-A-dependent macrophage adhesion, and suggest that by modifying the ECM, FAP plays a novel role in mediating communication between activated fibroblasts and macrophages. PMID:26934296

Cancer Prevention by Tocopherols and Tea Polyphenols

PubMed Central

Yang, Chung S.; Li, Guangxun; Yang, Zhihong; Guan, Fei; Chen, Amber; Ju, Jihyeung

2013-01-01

Tocopherols (vitamin E) and tea polyphenols have been reported to have cancer preventive activities. Large-scale human trials with high doses of alpha-tocopherol, however, have produced disappointing results. This review presents data showing that γ- and δ-tocopherols inhibit colon, lung, mammary and prostate carcinogenesis in animal models, whereas α-tocopherol is ineffective in animal and human studies. Possible mechanisms of action are discussed. A broad cancer preventive activity of green tea polyphenols has been demonstrated in animal models, and many mechanisms have been proposed. The cancer preventive activity of green tea in humans, however, has not been conclusively demonstrated and remains to be further investigated. PMID:23403075

The optimization of force inputs for active structural acoustic control using a neural network

NASA Technical Reports Server (NTRS)

Cabell, R. H.; Lester, H. C.; Silcox, R. J.

1992-01-01

This paper investigates the use of a neural network to determine which force actuators, of a multi-actuator array, are best activated in order to achieve structural-acoustic control. The concept is demonstrated using a cylinder/cavity model on which the control forces, produced by piezoelectric actuators, are applied with the objective of reducing the interior noise. A two-layer neural network is employed and the back propagation solution is compared with the results calculated by a conventional, least-squares optimization analysis. The ability of the neural network to accurately and efficiently control actuator activation for interior noise reduction is demonstrated.

Behaviour and Locomotor Activity of a Migratory Catostomid during Fishway Passage

PubMed Central

Silva, Ana T.; Hatry, Charles; Thiem, Jason D.; Gutowsky, Lee F. G.; Hatin, Daniel; Zhu, David Z.; W. Dawson, Jeffery; Katopodis, Christos; J. Cooke, Steven

2015-01-01

Fishways have been developed to restore longitudinal connectivity in rivers. Despite their potential for aiding fish passage, fishways may represent a source of significant energetic expenditure for fish as they are highly turbulent environments. Nonetheless, our understanding of the physiological mechanisms underpinning fishway passage of fish is still limited. We examined swimming behaviour and activity of silver redhorse (Moxostoma anisurum) during its upriver spawning migration in a vertical slot fishway. We used an accelerometer-derived instantaneous activity metric (overall dynamic body acceleration) to estimate location-specific swimming activity. Silver redhorse demonstrated progressive increases in activity during upstream fishway passage. Moreover, location-specific passage duration decreased with an increasing number of passage attempts. Turning basins and the most upstream basin were found to delay fish passage. No relationship was found between basin-specific passage duration and activity and the respective values from previous basins. The results demonstrate that successful fishway passage requires periods of high activity. The resultant energetic expenditure may affect fitness, foraging behaviour and increase susceptibility to predation, compromising population sustainability. This study highlights the need to understand the physiological mechanisms underpinning fishway passage to improve future designs and interpretation of biological evaluations. PMID:25853245

Endocrine Activities of Pesticides During Ozonation of Waters.

PubMed

Westlund, Paul; Isazadeh, Siavash; Therrien, Alexandre; Yargeau, Viviane

2018-01-01

Two yeast-based bioassays were used to assess the endocrine activity potential of transformation products formed during the ozonation of water containing a variety of pesticides (propiconazole, atrazine, 2,4-dichlorophenoxyacetic acid [2,4-D], tebuconazole, climbazole, myclobutanil, irgarol, terbutryn, dicamba, mecoprop and diuron). Ozone experiments were conducted first in reverse osmosis water to isolate the effects of the pesticides and then in synthetic wastewater and wastewater effluent to investigate whether the results translated to more complex matrices. The findings demonstrate the recalcitrant nature of most pesticides during ozonation, with removals below 50%, except for irgarol, terbutryn and climbazole with removals up to 70%. This study is the first one to investigate the removal of the fungicides myclobutanil and tebuconazole by ozonation and is one of the first studies to investigate the androgenic activity of ozonation transformation products of contaminants of emerging concern. These findings also demonstrated that during ozonation the initial anti-androgenic activity was removed while the estrogenic activity remained undetected and the androgenic activity increased to levels up to 60% of the anti-androgenic activity of the DHT control. These results indicate that bioactivity should be considered in the evaluation of treatment performance and risks assessment associated to wastewater discharges.

An Intracellular Peptidyl-Prolyl cis/trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease.

PubMed

Wiemels, Richard E; Cech, Stephanie M; Meyer, Nikki M; Burke, Caleb A; Weiss, Andy; Parks, Anastacia R; Shaw, Lindsey N; Carroll, Ronan K

2017-01-01

Staphylococcus aureus is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl cis/trans isomerases (PPIases) on the activity of the S. aureus secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of ppiB results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity in vitro, is localized to the bacterial cytosol, and directly interacts with Nuc in vitro to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in S. aureus hemolysis and demonstrate that the S. aureus parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of prsA leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in S. aureus IMPORTANCE: Staphylococcus aureus is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently, once outside the cell, they must refold into their active form. This step often requires the assistance of bacterial folding proteins, such as PPIases. In this work, we investigate the role of PPIases in S. aureus and uncover a cyclophilin-type enzyme that assists in the folding/refolding of staphylococcal nuclease. Copyright © 2016 American Society for Microbiology.

Activation of protein kinase C alters the intracellular distribution and mobility of cardiac Na+ channels.

PubMed

Hallaq, Haifa; Wang, Dao W; Kunic, Jennifer D; George, Alfred L; Wells, K Sam; Murray, Katherine T

2012-02-01

Na(+) current derived from expression of the cardiac isoform SCN5A is reduced by receptor-mediated or direct activation of protein kinase C (PKC). Previous work has suggested a possible role for loss of Na(+) channels at the plasma membrane in this effect, but the results are controversial. In this study, we tested the hypothesis that PKC activation acutely modulates the intracellular distribution of SCN5A channels and that this effect can be visualized in living cells. In human embryonic kidney cells that stably expressed SCN5A with green fluorescent protein (GFP) fused to the channel COOH-terminus (SCN5A-GFP), Na(+) currents were suppressed by an exposure to PKC activation. Using confocal microscopy, colocalization of SCN5A-GFP channels with the plasma membrane under control and stimulated conditions was quantified. A separate population of SCN5A channels containing an extracellular epitope was immunolabeled to permit temporally stable labeling of the plasma membrane. Our results demonstrated that Na(+) channels were preferentially trafficked away from the plasma membrane by PKC activation, with a major contribution by Ca(2+)-sensitive or conventional PKC isoforms, whereas stimulation of protein kinase A (PKA) had the opposite effect. Removal of the conserved PKC site Ser(1503) or exposure to the NADPH oxidase inhibitor apocynin eliminated the PKC-mediated effect to alter channel trafficking, indicating that both channel phosphorylation and ROS were required. Experiments using fluorescence recovery after photobleaching demonstrated that both PKC and PKA also modified channel mobility in a manner consistent with the dynamics of channel distribution. These results demonstrate that the activation of protein kinases can acutely regulate the intracellular distribution and molecular mobility of cardiac Na(+) channels in living cells.

In Vitro Virology Profile of Tenofovir Alafenamide, a Novel Oral Prodrug of Tenofovir with Improved Antiviral Activity Compared to That of Tenofovir Disoproxil Fumarate

PubMed Central

Stepan, George; Tian, Yang; Miller, Michael D.

2015-01-01

Tenofovir alafenamide (TAF) is an investigational oral prodrug of the HIV-1 nucleotide reverse transcriptase inhibitor tenofovir (TFV). Tenofovir disoproxil fumarate (TDF) is another TFV prodrug, widely used for the treatment of HIV-1 infection. TAF is converted mostly intracellularly to TFV and, in comparison to TDF, achieves higher tenofovir diphosphate (TFV-DP) levels in peripheral blood mononuclear cells. As a result, TAF has demonstrated potent anti-HIV-1 activity at lower doses than TDF in monotherapy studies. Here, the in vitro virology profile of TAF was evaluated and compared to that of TDF. TAF displayed potent antiviral activity against all HIV-1 groups/subtypes, as well as HIV-2. TAF exhibited minimal changes in the drug concentration needed to inhibit 50% of viral spread (EC50) upon removal of the prodrug, similar to TDF, demonstrating intracellular antiviral persistence. While TAF and TDF exhibited comparable potencies in the absence of serum pretreatment, TAF maintained activity in the presence of human serum, whereas TDF activity was significantly reduced. This result demonstrates TAF's improved plasma stability over TDF, which is driven by the different metabolic pathways of the two prodrugs and is key to TAF's improved in vivo antiviral activity. The activity of TAF is specific for HIV, as TAF lacked activity against a large panel of human viruses, with the exception of herpes simplex virus 2, where weak TAF antiviral activity was observed, as previously observed with TFV. Finally, in vitro combination studies with antiretroviral drugs from different classes showed additive to synergistic interactions with TAF, consistent with ongoing clinical studies with TAF in fixed-dose combinations with multiple other antiretroviral drugs for the treatment of HIV. PMID:26149992

Comparative Metabolomic Profiling Reveals That Dysregulated Glycolysis Stemming from Lack of Salvage NAD+ Biosynthesis Impairs Reproductive Development in Caenorhabditis elegans.

PubMed

Wang, Wenqing; McReynolds, Melanie R; Goncalves, Jimmy F; Shu, Muya; Dhondt, Ineke; Braeckman, Bart P; Lange, Stephanie E; Kho, Kelvin; Detwiler, Ariana C; Pacella, Marisa J; Hanna-Rose, Wendy

2015-10-23

Temporal developmental progression is highly coordinated in Caenorhabditis elegans. However, loss of nicotinamidase PNC-1 activity slows reproductive development, uncoupling it from its typical progression relative to the soma. Using LC/MS we demonstrate that pnc-1 mutants do not salvage the nicotinamide released by NAD(+) consumers to resynthesize NAD(+), resulting in a reduction in global NAD(+) bioavailability. We manipulate NAD(+) levels to demonstrate that a minor deficit in NAD(+) availability is incompatible with a normal pace of gonad development. The NAD(+) deficit compromises NAD(+) consumer activity, but we surprisingly found no functional link between consumer activity and reproductive development. As a result we turned to a comparative metabolomics approach to identify the cause of the developmental phenotype. We reveal widespread metabolic perturbations, and using complementary pharmacological and genetic approaches, we demonstrate that a glycolytic block accounts for the slow pace of reproductive development. Interestingly, mitochondria are protected from both the deficiency in NAD(+) biosynthesis and the effects of reduced glycolytic output. We suggest that compensatory metabolic processes that maintain mitochondrial activity in the absence of efficient glycolysis are incompatible with the requirements for reproductive development, which requires high levels of cell division. In addition to demonstrating metabolic requirements for reproductive development, this work also has implications for understanding the mechanisms behind therapeutic interventions that target NAD(+) salvage biosynthesis for the purposes of inhibiting tumor growth. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparative Metabolomic Profiling Reveals That Dysregulated Glycolysis Stemming from Lack of Salvage NAD+ Biosynthesis Impairs Reproductive Development in Caenorhabditis elegans*

PubMed Central

Wang, Wenqing; McReynolds, Melanie R.; Goncalves, Jimmy F.; Shu, Muya; Dhondt, Ineke; Braeckman, Bart P.; Lange, Stephanie E.; Kho, Kelvin; Detwiler, Ariana C.; Pacella, Marisa J.; Hanna-Rose, Wendy

2015-01-01

Temporal developmental progression is highly coordinated in Caenorhabditis elegans. However, loss of nicotinamidase PNC-1 activity slows reproductive development, uncoupling it from its typical progression relative to the soma. Using LC/MS we demonstrate that pnc-1 mutants do not salvage the nicotinamide released by NAD+ consumers to resynthesize NAD+, resulting in a reduction in global NAD+ bioavailability. We manipulate NAD+ levels to demonstrate that a minor deficit in NAD+ availability is incompatible with a normal pace of gonad development. The NAD+ deficit compromises NAD+ consumer activity, but we surprisingly found no functional link between consumer activity and reproductive development. As a result we turned to a comparative metabolomics approach to identify the cause of the developmental phenotype. We reveal widespread metabolic perturbations, and using complementary pharmacological and genetic approaches, we demonstrate that a glycolytic block accounts for the slow pace of reproductive development. Interestingly, mitochondria are protected from both the deficiency in NAD+ biosynthesis and the effects of reduced glycolytic output. We suggest that compensatory metabolic processes that maintain mitochondrial activity in the absence of efficient glycolysis are incompatible with the requirements for reproductive development, which requires high levels of cell division. In addition to demonstrating metabolic requirements for reproductive development, this work also has implications for understanding the mechanisms behind therapeutic interventions that target NAD+ salvage biosynthesis for the purposes of inhibiting tumor growth. PMID:26350462

The AAA protein spastin possesses two levels of basal ATPase activity.

PubMed

Fan, Xiangyu; Lin, Zhijie; Fan, Guanghui; Lu, Jing; Hou, Yongfei; Habai, Gulijiazi; Sun, Linyue; Yu, Pengpeng; Shen, Yuequan; Wen, Maorong; Wang, Chunguang

2018-05-01

The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected. © 2018 Federation of European Biochemical Societies.

Valproic acid exposure sequentially activates Wnt and mTOR pathways in rats.

PubMed

Qin, Liyan; Dai, Xufang; Yin, Yunhou

2016-09-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, limited verbal communication and repetitive behaviors. Recent studies have demonstrated that Wnt signaling and mTOR signaling play important roles in the pathogenesis of ASD. However, the relationship of these two signaling pathways in ASD remains unclear. We assessed this question using the valproic acid (VPA) rat model of autism. Our results demonstrated that VPA exposure activated mTOR signaling and suppressed autophagy in the prefrontal cortex, hippocampus and cerebellum of autistic model rats, characterized by enhanced phospho-mTOR and phospho-S6 and decreased Beclin1, Atg5, Atg10, LC3-II and autophagosome formation. Rapamycin treatment suppressed the effect of VPA on mTOR signaling and ameliorated the autistic-like behaviors of rats in our autism model. The administration of VPA also activated Wnt signaling through up-regulating beta-catenin and phospho-GSK3beta. Suppression of the Wnt pathway by sulindac relieved autistic-like behaviors and attenuated VPA-induced mTOR signaling activation in autistic model rats. Our results demonstrate that VPA exposure sequentially activates Wnt signaling and mTOR signaling in rats. Suppression of the Wnt signaling pathway relieves autistic-like behaviors partially by deactivating the mTOR signaling pathway in VPA-exposed rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Maraba MG1 Virus Enhances Natural Killer Cell Function via Conventional Dendritic Cells to Reduce Postoperative Metastatic Disease

PubMed Central

Zhang, Jiqing; Tai, Lee-Hwa; Ilkow, Carolina S; Alkayyal, Almohanad A; Ananth, Abhirami A; de Souza, Christiano Tanese; Wang, Jiahu; Sahi, Shalini; Ly, Lundi; Lefebvre, Charles; Falls, Theresa J; Stephenson, Kyle B; Mahmoud, Ahmad B; Makrigiannis, Andrew P; Lichty, Brian D; Bell, John C; Stojdl, David F; Auer, Rebecca C

2014-01-01

This study characterizes the ability of novel oncolytic rhabdoviruses (Maraba MG1) to boost natural killer (NK) cell activity. Our results demonstrate that MG1 activates NK cells via direct infection and maturation of conventional dendritic cells. Using NK depletion and conventional dendritic cells ablation studies in vivo, we established that both are required for MG1 efficacy. We further explored the efficacy of attenuated MG1 (nonreplicating MG1-UV2min and single-cycle replicating MG1-Gless) and demonstrated that these viruses activate conventional dendritic cells, although to a lesser extent than live MG1. This translates to equivalent abilities to remove tumor metastases only at the highest viral doses of attenuated MG1. In tandem, we characterized the antitumor ability of NK cells following preoperative administration of live and attenuated MG1. Our results demonstrates that a similar level of NK activation and reduction in postoperative tumor metastases was achieved with equivalent high viral doses concluding that viral replication is important, but not necessary for NK activation. Biochemical characterization of a panel of UV-inactivated MG1 (2–120 minutes) revealed that intact viral particle and target cell recognition are essential for NK cell–mediated antitumor responses. These findings provide mechanistic insight and preclinical rationale for safe perioperative virotherapy to effectively reduce metastatic disease following cancer surgery. PMID:24695102

Substance P provides neuroprotection in cerebellar granule cells through Akt and MAPK/Erk activation: evidence for the involvement of the delayed rectifier potassium current.

PubMed

Amadoro, G; Pieri, M; Ciotti, M T; Carunchio, I; Canu, N; Calissano, P; Zona, C; Severini, C

2007-05-01

In the current study, we have evaluated the ability of substance P (SP) and other neurokinin 1 receptor (NK1) agonists to protect, in a dose- and time-dependent manner, primary cultures of rat cerebellar granule cells (CGCs) from serum and potassium deprivation-induced cell death (S-K5). We also established the presence of SP high affinity NK1 transcripts and the NK1 protein localization in the membrane of a sub-population of CGCs. Moreover, SP significantly and dose-dependently reduced the Akt 1/2 and Erk1/2 dephosphorylation induced by S-K5 conditions, as demonstrated by Western blot analysis. Surprisingly, in SP-treated CGCs caspase-3 activity was not inhibited, while the calpain-1 activity was moderately reduced. Corroborating this result, SP blocked calpain-mediated cleavage of tau protein, as demonstrated by the reduced appearance of a diagnostic fragment of 17 kDa by Western blot analysis. In addition, SP induced a significant reduction of the delayed rectifier K+ currents (Ik) in about 42% of the patched neurons, when these were evoked with depolarizing potential steps. Taken together, the present results demonstrate that the activation of NK1 receptors expressed in CGCs promote the neuronal survival via pathways involving Akt and Erk activation and by inhibition of Ik which can contribute to the neuroprotective effect of the peptide.

Age differences in medial prefrontal activity for subsequent memory of truth value

PubMed Central

Cassidy, Brittany S.; Hedden, Trey; Yoon, Carolyn; Gutchess, Angela H.

2014-01-01

Much research has demonstrated that aging is marked by decreased source memory relative to young adults, yet a smaller body of work has demonstrated that increasing the socioemotional content of source information may be one way to reduce age-related performance differences. Although dorsomedial prefrontal cortex (dmPFC) activity may support source memory among young and older adults, the extent to which one activates dorsal vs. ventral mPFC may reflect one's personal connection with incoming information. Because truth value may be one salient marker that impacts one's connection with information and allocation of attention toward incoming material, we investigated whether the perceived truth value of information differently impacts differences in mPFC activity associated with encoding source information, particularly with age. Twelve young (18–23 years) and 12 older adults (63–80 years) encoded true and false statements. Behavioral results showed similar memory performance between the age groups. With respect to neural activity associated with subsequent memory, young adults, relative to older adults, exhibited greater activity in dmPFC while older adults displayed enhanced ventromedial prefrontal cortex (vmPFC) and insula engagement relative to young. These results may potentially indicate that young adults focus on a general knowledge acquisition goal, while older adults focus on emotionally relevant aspects of the material. The findings demonstrate that age-related differences in recruitment of mPFC associated with encoding source information may in some circumstances underlie age-equivalent behavioral performance. PMID:24570672

EPIGALLOCATECHIN-3-GALLATE (EGCG), A GREEN TEA POLYPHENOL, SUPPRESSES HEPATIC GLUCONEOGENESIS THROUGH 5′-AMP-ACTIVATED PROTEIN KINASE

PubMed Central

Collins, Qu Fan; Liu, Hui-Yu; Pi, Jingbo; Liu, Zhenqi; Quon, Michael J.; Cao, Wenhong

2008-01-01

Epigallocatechin-3-gallate (EGCG), a main catechin of green tea, has been suggested to inhibit hepatic gluconeogenesis. However, the exact role and related mechanism have not been established. In this study, we examined the role of EGCG in hepatic gluconeogenesis at concentrations that are reachable by ingestion of pure EGCG or green tea, and are not toxic to hepatocytes. Our results show in isolated hepatocytes that EGCG at relatively low concentrations (≤ 1 μM) inhibited glucose production via gluconeogenesis and expression of key gluconeogenic genes. EGCG was not toxic at these concentrations while demonstrating significant cytotoxicity at 10 μM and higher concentrations. EGCG at 1 μM or lower concentrations effective in suppressing hepatic gluconeogenesis did not activate the insulin signaling pathway, but activated 5′-AMP-activated protein kinase (AMPK). The EGCG suppression of hepatic gluconeogenesis was prevented by blockade of AMPK activity. In defining the mechanism by which EGCG activates AMPK, we found that the EGCG activation of AMPK was mediated by the Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Furthermore, our results show that the EGCG activation of AMPK and EGCG suppression of hepatic gluconeogenesis were both dependent on production of reactive oxygen species (ROS), which was a known activator of CaMKK. Together, our results demonstrate an inhibitory role for EGCG in hepatic gluconeogenesis and shed new light on the mechanism by which EGCG suppresses gluconeogenesis. PMID:17724029

Video- Demonstration of Seltzer Tablet in Water Onboard the International Space Station (ISS)

NASA Technical Reports Server (NTRS)

2002-01-01

Saturday Morning Science, the science of opportunity series of applied experiments and demonstrations, performed aboard the International Space Station (ISS) by Expedition 6 astronaut Dr. Don Pettit, revealed some remarkable findings. In this video clip, Pettit demonstrates dropping an Alka Seltzer tablet into a film of water which becomes a floating ball of activity filled water. Watch the video to see the surprising results!

Stabilization, not polymerization, of microtubules inhibits the nuclear translocation of STATs in adipocytes.

PubMed

Gleason, Evanna L; Hogan, Jessica C; Stephens, Jacqueline M

2004-12-17

Signal transducers and activators of transcriptions (STATs) are a family of latent transcription factors which are activated by a variety of growth factors and cytokines in many cell types. However, the mechanism by which these transcription factors translocate to the nucleus is poorly understood. The goal of this study was to determine the requirement of microfilaments and microtubules for cytokine induced STAT activation in cultured adipocytes. We used seven different actin-specific and microtubule-specific agents that are well-established effectors of these cytoskeletal networks. Our results clearly demonstrate that inhibition of microfilaments or the prevention of microtubule polymerization has no effect on the ability of STATs to be tyrosine phosphorylated or to translocate to the nucleus. However, we observed that paclitaxel, a microtubule stabilizer, resulted in a significant decrease in the nuclear translocation of STATs without affecting the cytosolic tyrosine phosphorylation of these transcription factors. In summary, our results demonstrate that the dynamic instability, but not the polymerization, of microtubules contributes to nuclear translocation of STAT proteins in adipocytes.

Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects

PubMed Central

Runtuwene, Vincent; van Eekelen, Mark; Overvoorde, John; Rehmann, Holger; Yntema, Helger G.; Nillesen, Willy M.; van Haeringen, Arie; van der Burgt, Ineke; Burgering, Boudewijn; den Hertog, Jeroen

2011-01-01

SUMMARY Noonan syndrome is a relatively common developmental disorder that is characterized by reduced growth, wide-set eyes and congenital heart defects. Noonan syndrome is associated with dysregulation of the Ras–mitogen-activated-protein-kinase (MAPK) signaling pathway. Recently, two mutations in NRAS were reported to be associated with Noonan syndrome, T50I and G60E. Here, we report a mutation in NRAS, resulting in an I24N amino acid substitution, that we identified in an individual bearing typical Noonan syndrome features. The I24N mutation activates N-Ras, resulting in enhanced downstream signaling. Expression of N-Ras-I24N, N-Ras-G60E or the strongly activating mutant N-Ras-G12V, which we included as a positive control, results in developmental defects in zebrafish embryos, demonstrating that these activating N-Ras mutants are sufficient to induce developmental disorders. The defects in zebrafish embryos are reminiscent of symptoms in individuals with Noonan syndrome and phenocopy the defects that other Noonan-syndrome-associated genes induce in zebrafish embryos. MEK inhibition completely rescued the activated N-Ras-induced phenotypes, demonstrating that these defects are mediated exclusively by Ras-MAPK signaling. In conclusion, mutations in NRAS from individuals with Noonan syndrome activated N-Ras signaling and induced developmental defects in zebrafish embryos, indicating that activating mutations in NRAS cause Noonan syndrome. PMID:21263000

Activity-Based Introductory Physics Reform *

NASA Astrophysics Data System (ADS)

Thornton, Ronald

2004-05-01

Physics education research has shown that learning environments that engage students and allow them to take an active part in their learning can lead to large conceptual gains compared to those of good traditional instruction. Examples of successful curricula and methods include Peer Instruction, Just in Time Teaching, RealTime Physics, Workshop Physics, Scale-Up, and Interactive Lecture Demonstrations (ILDs). RealTime Physics promotes interaction among students in a laboratory setting and makes use of powerful real-time data logging tools to teach concepts as well as quantitative relationships. An active learning environment is often difficult to achieve in large lecture sessions and Workshop Physics and Scale-Up largely eliminate lectures in favor of collaborative student activities. Peer Instruction, Just in Time Teaching, and Interactive Lecture Demonstrations (ILDs) make lectures more interactive in complementary ways. This presentation will introduce these reforms and use Interactive Lecture Demonstrations (ILDs) with the audience to illustrate the types of curricula and tools used in the curricula above. ILDs make use real experiments, real-time data logging tools and student interaction to create an active learning environment in large lecture classes. A short video of students involved in interactive lecture demonstrations will be shown. The results of research studies at various institutions to measure the effectiveness of these methods will be presented.

Embodied Action Improves Cognition in Children: Evidence from a Study Based on Piagetian Conservation Tasks.

PubMed

Lozada, Mariana; Carro, Natalia

2016-01-01

Converging evidence highlights the relevance of embodied cognition in learning processes. In this study we evaluate whether embodied action (enaction) improves cognitive understanding in children. Using the Piagetian conservation tasks in 6-7 year olds, we analyzed quantity conservation conceptualization in children who were active participants in the transformation process and compared these results to those of children who were mere observers of an adult's demonstration (as traditionally conducted). The investigation was performed with 105 first-graders. Conservation tasks were demonstrated to half the children, while the other half actively carried out the transformation of matter. Our findings showed that active manipulation of the material helped children recognize quantity invariance in a higher proportion than when the demonstration was only observed. That is, their enactive experience enabled them to comprehend conservation phenomena more easily than if they were merely passive observers. The outcome of this research thus emphasizes how active participation benefits cognitive processes in learning contexts, promoting autonomy, and agency during childhood.

Embodied Action Improves Cognition in Children: Evidence from a Study Based on Piagetian Conservation Tasks

PubMed Central

Lozada, Mariana; Carro, Natalia

2016-01-01

Converging evidence highlights the relevance of embodied cognition in learning processes. In this study we evaluate whether embodied action (enaction) improves cognitive understanding in children. Using the Piagetian conservation tasks in 6–7 year olds, we analyzed quantity conservation conceptualization in children who were active participants in the transformation process and compared these results to those of children who were mere observers of an adult's demonstration (as traditionally conducted). The investigation was performed with 105 first-graders. Conservation tasks were demonstrated to half the children, while the other half actively carried out the transformation of matter. Our findings showed that active manipulation of the material helped children recognize quantity invariance in a higher proportion than when the demonstration was only observed. That is, their enactive experience enabled them to comprehend conservation phenomena more easily than if they were merely passive observers. The outcome of this research thus emphasizes how active participation benefits cognitive processes in learning contexts, promoting autonomy, and agency during childhood. PMID:27047420

The ins and outs of breath holding: simple demonstrations of complex respiratory physiology.

PubMed

Skow, Rachel J; Day, Trevor A; Fuller, Jonathan E; Bruce, Christina D; Steinback, Craig D

2015-09-01

The physiology of breath holding is complex, and voluntary breath-hold duration is affected by many factors, including practice, psychology, respiratory chemoreflexes, and lung stretch. In this activity, we outline a number of simple laboratory activities or classroom demonstrations that illustrate the complexity of the integrative physiology behind breath-hold duration. These activities require minimal equipment and are easily adapted to small-group demonstrations or a larger-group inquiry format where students can design a protocol and collect and analyze data from their classmates. Specifically, breath-hold duration is measured during a number of maneuvers, including after end expiration, end inspiration, voluntary prior hyperventilation, and inspired hyperoxia. Further activities illustrate the potential contribution of chemoreflexes through rebreathing and repeated rebreathing after a maximum breath hold. The outcome measures resulting from each intervention are easily visualized and plotted and can comprise a comprehensive data set to illustrate and discuss complex and integrated cardiorespiratory physiology. Copyright © 2015 The American Physiological Society.

Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro

PubMed Central

Lv, Zhimei; Hu, Mengsi; Ren, Xiaoxu; Fan, Minghua; Zhen, Junhui; Chen, Liqun; Lin, Jiangong; Ding, Nannan; Wang, Qun; Wang, Rong

2016-01-01

Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation. PMID:26881253

PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose

PubMed Central

Tee, Sui Seng; Park, Jae Mo; Hurd, Ralph E.; Brimacombe, Kyle R.; Boxer, Matthew B.; Massoud, Tarik F.; Rutt, Brian K.; Spielman, Daniel M.

2017-01-01

Cancer metabolism has emerged as an increasingly attractive target for interfering with tumor growth. Small molecule activators of pyruvate kinase isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in increased glucose consumption, providing the rationale for combining PKM2 activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination treatment resulted in reduced viability of a range of cell lines in standard cell culture conditions at concentrations of drugs that had no effect when used alone. This effect was replicated in vivo on established subcutaneous tumors. We further demonstrated the ability to detect acute metabolic differences in combination treatment using hyperpolarized magnetic resonance spectroscopy (MRS). Combination treated tumors displayed a higher pyruvate to lactate 13C-label exchange 2 hr post-treatment. This ability to assess the effect of drugs non-invasively may accelerate the implementation and clinical translation of drugs that target cancer metabolism. PMID:29207616

Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy (DR) by Activating Classical Complement Pathway.

PubMed

Huang, Chao; Fisher, Kiera P; Hammer, Sandra S; Navitskaya, Svetlana; Blanchard, Gary J; Busik, Julia V

2018-06-04

Diabetic Retinopathy (DR) is a micro-vascular complication of diabetes and is the leading cause of vision loss in working-age adults. Recent studies have implicated the complement system as an emerging player in development of vascular damage and progression of DR. However, the role and activation of the complement system in DR is not well understood. Exosomes, small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma suggesting that they can participate in causing vascular damage associated with DR. We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway, and that the quantity of these exosomes is increased in diabetes. Moreover, we show that lack of IgG in exosomes results in a reduction of retinal vascular damage in diabetic mice. Together, the results of this study demonstrate that complement activation by IgG-laden plasma exosomes could contribute to the development of DR. © 2018 by the American Diabetes Association.

Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

PubMed

Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

1999-03-05

Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

Differential PKA activation and AKAP association determines cell fate in cancer cells

PubMed Central

2013-01-01

Background The dependence of malignant properties of colorectal cancer (CRC) cells on IGF1R signaling has been demonstrated and several IGF1R antagonists are currently in clinical trials. Recently, we identified a novel pathway in which cAMP independent PKA activation by TGFβ signaling resulted in the destabilization of survivin/XIAP complex leading to increased cell death. In this study, we evaluated the effect of IGF1R inhibition or activation on PKA activation and its downstream cell survival signaling mechanisms. Methods Small molecule IGF1R kinase inhibitor OSI-906 was used to test the effect of IGF1R inhibition on PKA activation, AKAP association and its downstream cell survival signaling. In a complementary approach, ligand mediated activation of IGF1R was performed and AKAP/PKA signaling was analyzed for their downstream survival effects. Results We demonstrate that the inhibition of IGF1R in the IGF1R-dependent CRC subset generates cell death through a novel mechanism involving TGFβ stimulated cAMP independent PKA activity that leads to disruption of cell survival by survivin/XIAP mediated inhibition of caspase activity. Importantly, ligand mediated activation of the IGF1R in CRC cells results in the generation of cAMP dependent PKA activity that functions in cell survival by inhibiting caspase activity. Therefore, this subset of CRC demonstrates 2 opposing pathways organized by 2 different AKAPs in the cytoplasm that both utilize activation of PKA in a manner that leads to different outcomes with respect to life and death. The cAMP independent PKA activation pathway is dependent upon mitochondrial AKAP149 for its apoptotic functions. In contrast, Praja2 (Pja2), an AKAP-like E3 ligase protein was identified as a key element in controlling cAMP dependent PKA activity and pro-survival signaling. Genetic manipulation of AKAP149 and Praja2 using siRNA KD had opposing effects on PKA activity and survivin/XIAP regulation. Conclusions We had identified 2 cytoplasmic pathways dependent upon the same enzymatic activity with opposite effects on cell fate in terms of life and death. Understanding the specific mechanistic functions of IGF1R with respect to determining the PKA survival functions would have potential for impact upon the development of new therapeutic strategies by exploiting the IGF1R/cAMP-PKA survival signaling in cancer. PMID:24083380

Public health guidelines for physical activity: is there an app for that? A review of android and apple app stores.

PubMed

Knight, Emily; Stuckey, Melanie I; Prapavessis, Harry; Petrella, Robert J

2015-05-21

Physical activity participation is an important behavior for modifying lifestyle-related disease risk. Mobile health apps for chronic disease management and prevention are being developed at a rapid rate. However, it is unclear whether these apps are evidence-based. Current public health recommendations for physical activity participation for adults highlight the importance of engaging in 150 minutes weekly of purposeful exercise, and muscle strengthening activities on at least 2 days of the week. The aims of the present review were to (1) identify available evidence-based physical activity apps, and (2) identify technological features that could be leveraged to improve health outcomes. iTunes and Google Play mobile app stores were searched using keyword and category searching during a single day (February 18, 2014) for physical activity apps available in English. The description pages of eligible apps were reviewed by 4 independent reviewers for evidence-based content, technological, and descriptive features. An a priori subset of apps was downloaded for further review (n=6 affiliated with a non-commercial agency; n=10 top rated; n=10 random selection), and developers were contacted for information regarding evidence-informed content. The initial search yielded 2400 apps, of which 379 apps (n=206 iTunes; n=173 Google Play) were eligible. Primary results demonstrated no apps (n=0) adhering to evidence-based guidelines for aerobic physical activity, and 7 out of 379 implementing evidence-based guidelines for resistance training physical activity. Technological features of apps included social networking (n=207), pairing with a peripheral health device (n=61), and measuring additional health parameters (n=139). Secondary results revealed 1 app that referenced physical activity guidelines (150 minutes/weekly of exercise), and demonstrated that apps were based on various physical activity reports (n=4) or personal expertise (n=2). The present study demonstrated a shortage of evidence-based physical activity apps. This gap underscores the need for development of evidence-informed mobile apps. Results highlight the opportunity to develop evidence-informed mobile apps that can be used clinically to enhance health outcomes.

Chemoenzymatic Synthesis of Heparin Oligosaccharides with both Anti-factor Xa and Anti-factor IIa Activities*

PubMed Central

Xu, Yongmei; Pempe, Elizabeth H.; Liu, Jian

2012-01-01

Heparan sulfate (HS) and heparin are highly sulfated polysaccharides. Heparin is a commonly used anticoagulant drug that inhibits the activities of factors Xa and IIa (also known as thrombin) to prevent blood clot formation. Here, we report the synthesis of a series of size-defined oligosaccharides to probe the minimum size requirement for an oligosaccharide with anti-IIa activity. The synthesis was completed by a chemoenzymatic approach involving glycosyltransferases, HS sulfotransferases, and C5-epimerase. We demonstrate the ability to synthesize highly purified N-sulfo-oligosaccharides having up to 21 saccharide residues. The results from anti-Xa and anti-IIa activity measurements revealed that an oligosaccharide longer than 19 saccharide residues is necessary to display anti-IIa activity. The oligosaccharides also exhibit low binding toward platelet factor 4, raising the possibility of preparing a synthetic heparin with a reduced effect of heparin-induced thrombocytopenia. The results from this study demonstrate the ability to synthesize large HS oligosaccharides and provide a unique tool to probe the structure and function relationships of HS that require the use of large HS fragments. PMID:22773834

Effects of brain-computer interface-based functional electrical stimulation on brain activation in stroke patients: a pilot randomized controlled trial.

PubMed

Chung, EunJung; Kim, Jung-Hee; Park, Dae-Sung; Lee, Byoung-Hee

2015-03-01

[Purpose] This study sought to determine the effects of brain-computer interface-based functional electrical stimulation (BCI-FES) on brain activation in patients with stroke. [Subjects] The subjects were randomized to in a BCI-FES group (n=5) and a functional electrical stimulation (FES) group (n=5). [Methods] Patients in the BCI-FES group received ankle dorsiflexion training with FES for 30 minutes per day, 5 times under the brain-computer interface-based program. The FES group received ankle dorsiflexion training with FES for the same amount of time. [Results] The BCI-FES group demonstrated significant differences in the frontopolar regions 1 and 2 attention indexes, and frontopolar 1 activation index. The FES group demonstrated no significant differences. There were significant differences in the frontopolar 1 region activation index between the two groups after the interventions. [Conclusion] The results of this study suggest that BCI-FES training may be more effective in stimulating brain activation than only FES training in patients recovering from stroke.

Dental resins properties studied by Bragg gratings

NASA Astrophysics Data System (ADS)

Kalinowski, Hypolito José; Gebert de Oliveira Franco, Ana Paula; Karam, Leandro Zen

2017-08-01

Fibre Bragg sensors are a key device in biomedical research for simultaneous measurement of deformations and temperature. The present study shows results from the characterization of dental resin materials with different composition and applications. The results show that all investigated polymer materials demonstrate a temperature rise within the first few seconds after starting activation procedure. The mode of activation and the material composition influence the polymerization shrinkage values.

Quorum Quenching: Enzymatic Disruption of N-Acylhomoserine Lactone-Mediated Bacterial Communication in Burkholderia thailandensis

DTIC Science & Technology

2004-10-01

lactonases failed to enhance beta-hemolytic activity. The results of this study demonstrate that heterologous expression of Bacillus sp . AiiA lactonases in...results of this study demonstrate that heterologous expression of Bacillus sp . AiiA lactonases in B. thailandensis reduced AHL accumulation, affected both...hemo- lysis, and carbon utilization by the expression of Bacillus sp . AiiA lactonases in B. thailandensis. MATERIALS AND METHODS Bacterial strains and

Active Structural Fibers for Multifunctional Composite Materials

DTIC Science & Technology

2014-05-06

capacitors. Lastly, a cathodic electrolytic deposition process has been investigated for the coating of carbon fibers with a PZT shell. The...results have demonstrated the ability to use the process to coat fibers with a thin shell of PZT . The results thus far have demonstrated the feasibility...Journal of Composite Materials, In Review. 2. Zhou, Z., Lin, Y. and Sodano, H.A., Synthesis and Characterization of Textured BaTiO3 Thin Films

Multiple autophosphorylations significantly enhance the endoribonuclease activity of human inositol requiring enzyme 1α

PubMed Central

2014-01-01

Background Endoplasmic reticulum stress, caused by the presence of misfolded proteins, activates the stress sensor inositol-requiring enzyme 1α (IRE1α). The resulting increase in IRE1α RNase activity causes sequence-specific cleavage of X-box binding protein 1 (XBP1) mRNA, resulting in upregulation of the unfolded protein response and cellular adaptation to stress. The precise mechanism of human IRE1α activation is currently unclear. The role of IRE1α kinase activity is disputed, as results from the generation of various kinase-inactivating mutations in either yeast or human cells are discordant. Kinase activity can also be made redundant by small molecules which bind the ATP binding site. We set out to uncover a role for IRE1α kinase activity using wild-type cytosolic protein constructs. Results We show that concentration-dependent oligomerisation is sufficient to cause IRE1α cytosolic domain RNase activity in vitro. We demonstrate a role for the kinase activity by showing that autophosphorylation enhances RNase activity. Inclusion of the IRE1α linker domain in protein constructs allows hyperphosphorylation and further enhancement of RNase activity, highlighting the importance of kinase activity. We show that IRE1α phosphorylation status correlates with an increased propensity to form oligomeric complexes and that forced dimerisation causes great enhancement in RNase activity. In addition we demonstrate that even when IRE1α is forced to dimerise, by a GST-tag, phospho-enhancement of activity is still observed. Conclusions Taken together these experiments support the hypothesis that phosphorylation is important in modulating IRE1α RNase activity which is achieved by increasing the propensity of IRE1α to dimerise. This work supports the development of IRE1α kinase inhibitors for use in the treatment of secretory cancers. PMID:24524643

Catalase and superoxide dismutase activities after heat injury of listeria monocytogenes

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

Dallmier, A.W.; Martin, S.E.

1988-02-01

Four strains of Listeria monocytogenes were examined for catalase (CA) and superoxide dismutase (SOD) activities. The two strains having the highest CA activities (LCDC and Scott A) also possessed the highest SOD activities. The CA activity of heated cell extracts of all four strains examined decreased sharply between 55 and 60/sup 0/C. SOD was more heat labile than CA. Two L. monocytogenes strains demonstrated a decline in SOD activity after heat treatment at 45/sup 0/C, whereas the other two strains demonstrated a decline at 50/sup 0/C. Sublethal heating of the cells at 55/sup 0/C resulted in increased sensitivity to 5.5%more » NaCl. Exogenous hydrogen peroxide was added to suspensions of L. monocytogenes; strains producing the highest CA levels showed the greatest H/sub 2/O/sub 2/ resistance.« less

Increased premotor cortex activation in high functioning autism during action observation.

PubMed

Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

2015-04-01

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Transcriptional activation of JC virus by human T-lymphotropic virus type I Tax protein in human neuronal cell lines.

PubMed

Okada, Y; Sawa, H; Tanaka, S; Takada, A; Suzuki, S; Hasegawa, H; Umemura, T; Fujisawa, J; Tanaka, Y; Hall, W W; Nagashima, K

2000-06-02

Polyomavirus JC (JCV) causes the human demyelinating disease, progressive multifocal leukoencephalopathy (PML). The recent demonstration of cases of PML in association with human T-lymphotropic virus type I (HTLV-I) infection prompted us to examine whether the HTLV-I-encoded regulatory protein Tax activates JCV transcription. By employing a dual luciferase assay, we initially found that the expression of Tax activated the transcriptional potential of both early and late promoters of JCV in human neuronal but not in non-neuronal cells. We subsequently analyzed the mechanism of Tax-induced activation of the JCV promoter in neuronal cells with the following results: 1) the JCV promoter that lacks the NF-kappaB-binding motif could not be activated by Tax; 2) the overexpression of IkappaBalpha abolished Tax-induced transcriptional activation of the JCV promoter; 3) a Tax mutant (M22) lacking the potential for activation via the NF-kappaB pathway did not activate the JCV promoter. Furthermore, Tax enhances the gene expression of JCV T antigen and VP1. We examined mechanisms of the cell-specific activation of the JCV promoter by Tax. Electrophoretic mobility shift assay demonstrated the presence of Tax-bound protein(s) that were specifically present in non-neuronal cells. This study is the first demonstration of the activation of JCV promoter by HTLV-I Tax in an NF-kappaB-dependent manner.

ARSENIC REMOVAL FROM DRINKING WATER BY PROCESS MODIFICATION TO COAGULATION/FILTRATION. USEPA DEMONSTRATION PROJECT AT LIDGERWOOD, ND. FINAL PERFORMANCE EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at the Lidgerwood, North Dakota site. The objectives of the project were to evaluate: (1) the effectiveness of process modifications to an e...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Dummerston, VT Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at Charette Mobile Home Park (CMHP) in Dummerston, Vermont. The objectives of the project were to evaluate: (1) the effectiveness of an Aqua...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA U.S. EPA DEMONSTRATION PROJECT AT DUMMERSTON, VT SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months (from June 22, 2005 through December 22, 2005) of the arsenic removal treatment technology demonstration project at Charette Mobile Home Park (CMHP) in Dummerston, Vermont. T...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Brown City, MI Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project in Brown City, MI. The objectives of the project were to evaluate (1) the effectiveness of a Severn Trent Services (STS) adsorptive media s...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA -- USEPA DEMONSTRATION PROJECT AT ROLLINSFORD, NH, SIX MONTH EVALUTION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the Rollinsford Water and Sewer District facility in Rollinsford, NH. The objectives of the project are to...

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Goffstown, NH, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at the Orchard Highlands Subdivision site in Goffstown, NH. The main objective of the project was to evaluate the effectiveness of AdEdge T...

Arsenic Removal from Drinking Water by Adsorptive Media, U.S. EPA Demonstration Project at Lead, South Dakota - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at Lead, South Dakota. The main objective of the project was to evaluate the effectiveness of SolmeteX’s adsorptive media system in removin...

Arsenic Removal from Drinking Water by Coagulation/Filtration - U.S. EPA Demonstration Project at Town of Arnaudville, LA - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at the United Water Systems’ facility in Arnaudville, LA. The objectives of the project were to evaluate: (1) the effectiveness of K...

Arsenic Removal from Drinking Water by Coagulation/Filtration U.S. EPA Demonstration Project at Sandusky, MI Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the U.S. Environmental Protection Agency (EPA) arsenic removal technology demonstration project at the City of Sandusky, MI facility. The objectives of the project were to evaluate: 1) the effect...

Arsenic Removal from Drinking Water by Coagulation/Filtration - U.S. EPA Demonstration Project at Village of Waynesville, IL - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal drinking water treatment technology demonstration project at the Village of Waynesville, IL. The main objective of the project was to evaluate the effectiveness of the Peerless coagu...

ARSENIC REMOVAL FROM DRINKING WATER BY IRON REMOVAL. USEPA DEMONSTRATION PROJECT AT CLIMAX, MN SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the Climax, MN site. The objectives of the project are to evaluate (1) the effectiveness of Kinetico’s Macrolite®...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA U.S. EPA DEMONSTRATION PROJECT AT BRUNI, TX, SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the Webb Consolidated Independent School District (Webb CISD) site at Bruni, TX. The main objective of the projec...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA. USEPA DEMONSTRATION PROJECT AT VALLEY VISTA, AZ FINAL PERFORMANCE EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at an Arizona Water Company (AWC) facility in Sedona, AZ, commonly referred to as Valley Vista. The objectives of the project were t...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA USEPA DEMONSTRATION PROJECT AT VALLEY VISTA, AZ SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the EPA arsenic removal technology demonstration project at the Arizona Water Company (AWC) facility in Sedona, AZ, commonly referred to as Valley Vista. The main objective of the...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA. U.S. EPA DEMONSTRATION PROJECT AT BOW, NH , SIX MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the White Rock Water Company (WRWC) public water system, a small residential drinking water facility in Bo...

ARSENIC REMOVAL FROM DRINKING WATER BY IRON REMOVAL. U.S. EPA DEMONSTRATION PROJECT AT CLIMAX, MN. FINAL PERFORMANCE EVALUATION REPORT.

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project following one year of operation at the Climax, Minnesota, site. The objectives of the project were to evaluate: (1) the effectiveness of Kin...

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Rollinsford, NH, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at Rollinsford, New Hampshire. The objectives of the project were to evaluate: 1) the effectiveness of AdEdge Technologies’ AD -33TM media ...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTION MEDIA USEPA DEMONSTRATION PROJECT AT BROWN CITY, MI SIX MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the arsenic removal treatment technology demonstration project in Brown City, MI. The objectives of the project are to evaluate the effectiveness of Severn Trent Services (...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA, USEPA DEMONSTRATION PROJECT AT RIMROCK, AZ, SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at Rimrock, AZ. The objectives of the project are to evaluate the effectiveness of AdEdge Arsenic Package Uni...

Arsenic Removal from Drinking Water by Absorptive Media-U.S. EPA Demonstration Project at Desert Sands MDWCA, NM Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at the Desert Sands Mutual Domestic Water Consumers Association (MDWCA) facility in Anthony, NM. The objectives of the project were to evalu...

Synthesis and Antibacterial Activity of Quaternary Ammonium 4-Deoxypyridoxine Derivatives

PubMed Central

Shtyrlin, Nikita V.; Sapozhnikov, Sergey V.; Galiullina, Albina S.; Kayumov, Airat R.; Bondar, Oksana V.; Mirchink, Elena P.; Isakova, Elena B.; Firsov, Alexander A.; Balakin, Konstantin V.

2016-01-01

A series of novel quaternary ammonium 4-deoxypyridoxine derivatives was synthesized. Two compounds demonstrated excellent activity against a panel of Gram-positive methicillin-resistant S. aureus strains with MICs in the range of 0.5–2 μg/mL, exceeding the activity of miramistin. At the same time, both compounds were inactive against the Gram-negative E. coli and P. aeruginosa strains. Cytotoxicity studies on human skin fibroblasts and embryonic kidney cells demonstrated that the active compounds possessed similar toxicity with benzalkonium chloride but were slightly more toxic than miramistin. SOS-chromotest in S. typhimurium showed the lack of DNA-damage activity of both compounds; meanwhile, one compound showed some mutagenic potential in the Ames test. The obtained results make the described chemotype a promising starting point for the development of new antibacterial therapies. PMID:27800491

Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation.

PubMed

Dong, Hongquan; Zhang, Xiang; Wang, Yiming; Zhou, Xiqiao; Qian, Yanning; Zhang, Shu

2017-03-01

Brain inflammation has a critical role in the pathophysiology of brain diseases. Microglia, the resident immune cells in the brain, play an important role in brain inflammation, while brain mast cells are the "first responder" in the injury rather than microglia. Functional aspects of mast cell-microglia interactions remain poorly understood. Our results demonstrated that site-directed injection of the "mast cell degranulator" compound 48/80 (C48/80) in the hypothalamus induced mast cell degranulation, microglial activation, and inflammatory factor production, which initiated the acute brain inflammatory response. "Mast cell stabilizer" disodium cromoglycate (cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced microglial activation, inhibition of MAPK and AKT pathways, and repression of protein expression of histamine receptor 1 (H 1 R), histamine receptor 4 (H 4 R), protease-activated receptor 2 (PAR2), and toll-like receptor 4 (TLR4) in microglia. We also demonstrated that C48/80 had no effect on microglial activation in mast cell-deficient Kit W-sh/W-sh mice. These results implicate that activated brain mast cells trigger microglial activation and stabilization of mast cell inhibits microglial activation-induced central nervous system (CNS) inflammation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS immune inflammation-related diseases.

Controlling Buffeting Loads by Rudder and Piezo-Actuation

NASA Technical Reports Server (NTRS)

Moses, Robert W.; Pototzky, Anthony S.; Henderson, Douglas A.; Galea, Stephen C.; Manokaran, Donald S.; Zimcik, David G.; Wickramasinghe, Viresh; Pitt, Dale M.; Gamble, Michael A.

2005-01-01

High performance aircraft, especially those with twin vertical tails, encounter unsteady buffet loads when flying at high angles of attack. These stochastic loads result in significant stresses, which may cause fatigue damage leading to restricted capabilities and availability of the aircraft. An international collaborative research activity among Australia, Canada and the United States, conducted under the auspices of The Technical Cooperation Program (TTCP) contributed resources toward a program that coalesced a broad range of technical knowledge and expertise into a single investigation to demonstrate the enhanced performance and capability of the advanced active Buffet Load Alleviation ( ) control system in preparation for a flight test demonstration. The research team investigated the use of active structural control to alleviate the damaging structural response to these loads by applying advanced directional piezoelectric actuators, the aircraft rudder, switch mode amplifiers, and advanced control strategies on an F/A-18 aircraft empennage. Some results of the full-scale investigation are presented herein.

Regulation of flagellar assembly by glycogen synthase kinase 3 in Chlamydomonas reinhardtii.

PubMed

Wilson, Nedra F; Lefebvre, Paul A

2004-10-01

Chlamydomonas reinhardtii controls flagellar assembly such that flagella are of an equal and predetermined length. Previous studies demonstrated that lithium, an inhibitor of glycogen synthase kinase 3 (GSK3), induced flagellar elongation, suggesting that a lithium-sensitive signal transduction pathway regulated flagellar length (S. Nakamura, H. Takino, and M. K. Kojima, Cell Struct. Funct. 12:369-374, 1987). Here, we demonstrate that lithium treatment depletes the pool of flagellar proteins from the cell body and that the heterotrimeric kinesin Fla10p accumulates in flagella. We identify GSK3 in Chlamydomonas and demonstrate that its kinase activity is inhibited by lithium in vitro. The tyrosine-phosphorylated, active form of GSK3 was enriched in flagella and GSK3 associated with the axoneme in a phosphorylation-dependent manner. The level of active GSK3 correlated with flagellar length; early during flagellar regeneration, active GSK3 increased over basal levels. This increase in active GSK3 was rapidly lost within 30 min of regeneration as the level of active GSK3 decreased relative to the predeflagellation level. Taken together, these results suggest a possible role for GSK3 in regulating the assembly and length of flagella.

ADVANCED UTILITY SIMULATION MODEL, REPORT OF SENSITIVITY TESTING, CALIBRATION, AND MODEL OUTPUT COMPARISONS (VERSION 3.0)

EPA Science Inventory

The report gives results of activities relating to the Advanced Utility Simulation Model (AUSM): sensitivity testing. comparison with a mature electric utility model, and calibration to historical emissions. The activities were aimed at demonstrating AUSM's validity over input va...

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

ERIC Educational Resources Information Center

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

2010-01-01

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

EFFECT OF DISSOLVED OXYGEN ON PHENOLS BREAKTHROUGH FROM GAC ADSORBERS

EPA Science Inventory

This study demonstrates that molecular oxygen plays an important role in the adsorption of organic compounds from water by activated carbon. It was determined that the adsorptive capacity of granular activated carbon (GAC) for o-cresol can increase by almost 200% as a result of...

Wind tunnel and field evaluation of drift from aerial spray applications with multiple spray formulations

USDA-ARS?s Scientific Manuscript database

The impact of different spray tank modifiers into an active ingredient spray mixture on spray atomization and in-field behavior under aerial application conditions were examined. Wind tunnel tests demonstrated that active ingredient solutions potentially results in significantly different atomizati...

Isolation and antitumor efficacy evaluation of a polysaccharide from Nostoc commune Vauch.

PubMed

Guo, Min; Ding, Guo-Bin; Guo, Songjia; Li, Zhuoyu; Zhao, Liangqi; Li, Ke; Guo, Xiangrong

2015-09-01

Nostoc commune Vauch. has been traditionally used as a healthy food and medicine for centuries especially in China. It has been demonstrated that the polysaccharides isolated from Nostoc commune Vauch. exhibit strong antimicrobial and antioxidant activities. However, little is known about their anticancer activities and the underlying mechanisms of action. Herein, we report the isolation of a polysaccharide from Nostoc commune Vauch. (NVPS), and its physicochemical properties were analyzed. In an attempt to demonstrate the potential application of NVPS in tumor chemotherapy, the in vitro antitumor activity was determined. NVPS significantly suppressed the growth and proliferation of MCF-7 and DLD1 cells. The molecular mechanism underlying this in vitro antitumor efficacy was elucidated, and the results indicated that NVPS simultaneously triggered intrinsic, extrinsic and endoplasmic reticulum stress (ERS)-mediated apoptotic signaling pathways. Collectively, these findings demonstrate that NVPS could be used as a novel promising source of natural antitumor agents.

Lysophosphatidic Acid Initiates Epithelial to Mesenchymal Transition and Induces β-Catenin-mediated Transcription in Epithelial Ovarian Carcinoma*

PubMed Central

Burkhalter, Rebecca J.; Westfall, Suzanne D.; Liu, Yueying; Stack, M. Sharon

2015-01-01

During tumor progression, epithelial ovarian cancer (EOC) cells undergo epithelial-to-mesenchymal transition (EMT), which influences metastatic success. Mutation-dependent activation of Wnt/β-catenin signaling has been implicated in gain of mesenchymal phenotype and loss of differentiation in several solid tumors; however, similar mutations are rare in most EOC histotypes. Nevertheless, evidence for activated Wnt/β-catenin signaling in EOC has been reported, and immunohistochemical analysis of human EOC tumors demonstrates nuclear staining in all histotypes. This study addresses the hypothesis that the bioactive lipid lysophosphatidic acid (LPA), prevalent in the EOC microenvironment, functions to regulate EMT in EOC. Our results demonstrate that LPA induces loss of junctional β-catenin, stimulates clustering of β1 integrins, and enhances the conformationally active population of surface β1 integrins. Furthermore, LPA treatment initiates nuclear translocation of β-catenin and transcriptional activation of Wnt/β-catenin target genes resulting in gain of mesenchymal marker expression. Together these data suggest that LPA initiates EMT in ovarian tumors through β1-integrin-dependent activation of Wnt/β-catenin signaling, providing a novel mechanism for mutation-independent activation of this pathway in EOC progression. PMID:26175151

Shikonin Suppresses NLRP3 and AIM2 Inflammasomes by Direct Inhibition of Caspase-1

PubMed Central

Zorman, Jernej; Sušjan, Petra; Hafner-Bratkovič, Iva

2016-01-01

Shikonin is a highly lipophilic naphtoquinone found in the roots of Lithospermum erythrorhizon used for its pleiotropic effects in traditional Chinese medicine. Based on its reported antipyretic and anti-inflammatory properties, we investigated whether shikonin suppresses the activation of NLRP3 inflammasome. Inflammasomes are cytosolic protein complexes that serve as scaffolds for recruitment and activation of caspase-1, which, in turn, results in cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. NLRP3 inflammasome activation involves two steps: priming, i.e. the activation of NF-κB pathway, and inflammasome assembly. While shikonin has previously been reported to suppress the priming step, we demonstrated that shikonin also inhibits the second step of inflammasome activation induced by soluble and particulate NLRP3 instigators in primed immortalized murine bone marrow-derived macrophages. Shikonin decreased NLRP3 inflammasome activation in response to nigericin more potently than acetylshikonin. Our results showed that shikonin also inhibits AIM2 inflammasome activation by double stranded DNA. Shikonin inhibited ASC speck formation and caspase-1 activation in murine macrophages and suppressed the activity of isolated caspase-1, demonstrating that it directly targets caspase-1. Complexing shikonin with β-lactoglobulin reduced its toxicity while preserving the inhibitory effect on NLRP3 inflammasome activation, suggesting that shikonin with improved bioavailability might be interesting for therapeutic applications in inflammasome-mediated conditions. PMID:27467658

Brain-computer interface for alertness estimation and improving

NASA Astrophysics Data System (ADS)

Hramov, Alexander; Maksimenko, Vladimir; Hramova, Marina

2018-02-01

Using wavelet analysis of the signals of electrical brain activity (EEG), we study the processes of neural activity, associated with perception of visual stimuli. We demonstrate that the brain can process visual stimuli in two scenarios: (i) perception is characterized by destruction of the alpha-waves and increase in the high-frequency (beta) activity, (ii) the beta-rhythm is not well pronounced, while the alpha-wave energy remains unchanged. The special experiments show that the motivation factor initiates the first scenario, explained by the increasing alertness. Based on the obtained results we build the brain-computer interface and demonstrate how the degree of the alertness can be estimated and controlled in real experiment.

Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition.

PubMed

Qing, Hua; Aono, Jun; Findeisen, Hannes M; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

2016-06-01

Telomerase reverse transcriptase (TERT) maintains telomeres and is rate limiting for replicative life span. While most somatic tissues silence TERT transcription resulting in telomere shortening, cells derived from cancer or cardiovascular diseases express TERT and activate telomerase. In the present study, we demonstrate that histone deacetylase (HDAC) inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Finally, we demonstrate that HDAC inhibition decreases TERT expression during vascular remodeling in vivo. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition and suggest that TERT may constitute an important target for the anti-proliferative efficacy of HDAC inhibitors. © 2015 Wiley Periodicals, Inc.

A DEMETER-like DNA demethylase governs tomato fruit ripening.

PubMed

Liu, Ruie; How-Kit, Alexandre; Stammitti, Linda; Teyssier, Emeline; Rolin, Dominique; Mortain-Bertrand, Anne; Halle, Stefanie; Liu, Mingchun; Kong, Junhua; Wu, Chaoqun; Degraeve-Guibault, Charlotte; Chapman, Natalie H; Maucourt, Mickael; Hodgman, T Charlie; Tost, Jörg; Bouzayen, Mondher; Hong, Yiguo; Seymour, Graham B; Giovannoni, James J; Gallusci, Philippe

2015-08-25

In plants, genomic DNA methylation which contributes to development and stress responses can be actively removed by DEMETER-like DNA demethylases (DMLs). Indeed, in Arabidopsis DMLs are important for maternal imprinting and endosperm demethylation, but only a few studies demonstrate the developmental roles of active DNA demethylation conclusively in this plant. Here, we show a direct cause and effect relationship between active DNA demethylation mainly mediated by the tomato DML, SlDML2, and fruit ripening- an important developmental process unique to plants. RNAi SlDML2 knockdown results in ripening inhibition via hypermethylation and repression of the expression of genes encoding ripening transcription factors and rate-limiting enzymes of key biochemical processes such as carotenoid synthesis. Our data demonstrate that active DNA demethylation is central to the control of ripening in tomato.

Disruption of plastid acyl:acyl carrier protein synthetases increases medium chain fatty acid accumulation in seeds of transgenic Arabidopsis.

PubMed

Tjellström, Henrik; Strawsine, Merissa; Silva, Jillian; Cahoon, Edgar B; Ohlrogge, John B

2013-04-02

Engineering transgenic plants that accumulate high levels of medium-chain fatty acids (MCFA) has been least successful for shorter chain lengths (e.g., C8). We demonstrate that one limitation is the activity of acyl-ACP synthetase (AAE) that re-activates fatty acids released by acyl-ACP thioesterases. Seed expression of Cuphea pulcherrima FATB acyl-ACP thioesterase in a double mutant lacking AAE15/16 increased 8:0 accumulation almost 2-fold compared to expression in wild type. These results also provide an in planta demonstration that AAE enzymes participate not only in activation of exogenously added MCFA but also in activation of MCFA synthesized in plastids. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Mechanisms and functional implications of motoneuron adaptations to increased physical activity.

PubMed

MacDonell, Christopher; Gardiner, Phillip

2018-06-01

Motoneurons demonstrate adaptations in their physiological properties to alterations in chronic activity levels. The most consistent change that appears to result from endurance-type exercise training is the reduced excitatory current required to initiate and maintain rhythmic firing. While the precise mechanisms through which these neurons adapt to activity are currently unknown, evidence exists that adaptation may involve alterations in the expression of genes that code for membrane receptors which can influence the responses of neurons to transmitters during activation. The influence of these adaptations may also extend to the resting condition, where ambient levels of neuroactive substances may influence ion conductances at rest, and thus result in the activation or inhibition of specific ion conductances that underlie the measurements of increased excitability that have been reported for motoneurons in the anesthetised state. We have applied motoneuron excitability and muscle unit contractile changes with endurance training to a mathematical computerised model of motor unit recruitment (Heckman and Binder, 1991). The results from the modelling exercise demonstrate increased task efficiency at relative levels of effort during a submaximal contraction. The physiological impact that nerve and muscle adaptations have on the neuromuscular system during standardized tasks seem to fit with reported changes in motor unit behaviour in trained human subjects.

Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria.

PubMed

Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark

2016-01-28

Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. Copyright © 2015 Elsevier B.V. All rights reserved.

Kinetics of autothermal thermophilic aerobic digestion - application and extension of Activated Sludge Model No 1 at thermophilic temperatures.

PubMed

Kovács, R; Miháltz, P; Csikor, Zs

2007-01-01

The application of an ASM1-based mathematical model for the modeling of autothermal thermophilic aerobic digestion is demonstrated. Based on former experimental results the original ASM1 was extended by the activation of facultative thermophiles from the feed sludge and a new component, the thermophilic biomass was introduced. The resulting model was calibrated in the temperature range of 20-60 degrees C. The temperature dependence of the growth and decay rates in the model is given in terms of the slightly modified Arrhenius and Topiwala-Sinclair equations. The capabilities of the calibrated model in realistic ATAD scenarios are demonstrated with a focus on autothermal properties of ATAD systems at different conditions.

Post-test evaluation of the geology, geochemistry, microbiology, and hydrology of the in situ air stripping demonstration site at the Savannah River Site

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

Eddy Dilek, C.A.; Looney, B.B.; Hazen, T.C.

A full-scale demonstration of the use of horizontal wells for in situ air stripping for environment restoration was completed as part of the Savannah River Integrated Demonstration Program. The demonstration of in situ air stripping was the first in a series of demonstrations of innovative remediation technologies for the cleanup of sites contaminated with volatile organic contaminants. The in situ air stripping system consisted of two directionally drilled wells that delivered gases to and extract contamination from the subsurface. The demonstration was designed to remediate soils and sediments in the unsaturated and saturated zones as well as groundwater contaminated withmore » volatile organic compounds. The demonstration successfully removed significant quantities of solvent from the subsurface. The field site and horizontal wells were subsequently used for an in situ bioremediation demonstration during which methane was added to the injected air. The field conditions documented herein represent the baseline status of the site for evaluating the in situ bioremediation as well as the post-test conditions for the in situ air stripping demonstration. Characterization activities focused on documenting the nature and distribution of contamination in the subsurface. The post-test characterization activities discussed herein include results from the analysis of sediment samples, three-dimensional images of the pretest and post-test data, contaminant inventories estimated from pretest and post-test models, a detailed lithologic cross sections of the site, results of aquifer testing, and measurements of geotechnical parameters of undisturbed core sediments.« less

Using Regulation Activities to Improve Undergraduate Collaborative Writing on Wikis

ERIC Educational Resources Information Center

Cho, Moon-Heum; Lim, Seongmi

2017-01-01

Although wikis have been widely adopted to support collaborative writing in undergraduate classrooms, educators remain concerned about the level of student participation. Using regulation theories to design interventions in the form of activities, we examined their effects on collaborative writing on wikis. Results demonstrate that with the…

Keeping Teachers Current Through In-Service Aerospace Workshops.

ERIC Educational Resources Information Center

Herzer, Harry B., III

This paper reports on the educational activities of NASA's Educational Program Division and its Aerospace Education Services Project. Recognizing the vast explosion of knowledge resulting from the activities of the Space Program, these organizations have provided lecture-demonstrations for students and teachers to enable them to understand the…

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating.

PubMed

Josef Golubic, Sanja; Aine, Cheryl J; Stephen, Julia M; Adair, John C; Knoefel, Janice E; Supek, Selma

2017-10-01

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180-5194, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Antimicrobial activity of plant extracts against the honeybee pathogens, Paenibacillus larvae and Ascosphaera apis and their topical toxicity to Apis mellifera adults.

PubMed

Chaimanee, V; Thongtue, U; Sornmai, N; Songsri, S; Pettis, J S

2017-11-01

To explore alternative nonchemical control measures against two honeybee pathogens, Paenibacillus larvae and Ascosphaera apis, 37 plant species were screened for antimicrobial activity. The activity of selected plant extracts was screened using an in vitro disc diffusion assay and the minimal inhibitory concentration (MIC) was determined by the broth microdilution method. The results showed that 36 plant extracts had some antibacterial activity on P. larvae by disc diffusion assay. Chromolaena odorata showed the greatest antibacterial activity against P. larvae (MIC 16-64 μg ml -1 ). Of the 37 tested plants, only seven species, Amomum krervanh, Allium sativum, Cinnamomum sp., Piper betle, Piper ribesioides, Piper sarmentosum and Syzygium aromaticum had inhibitory effects on A. apis (MICs of 32-64 μg ml -1 ). The results demonstrated that promising plant extracts were not toxic to adult bees at the concentrations used in this study. The results demonstrate the potential antimicrobial activity of natural products against honeybee diseases caused by P. larvae and A. apis. Chromolaena odorata in particular showed high bioactivity against P. larvae. Further study is recommended to develop these nonchemical treatments against American foulbrood and chalkbrood in honeybees. This work proposes new natural products for the control of American foulbrood and chalkbrood in honeybees. © 2017 The Society for Applied Microbiology.

Synemin promotes AKT-dependent glioblastoma cell proliferation by antagonizing PP2A.

PubMed

Pitre, Aaron; Davis, Nathan; Paul, Madhumita; Orr, A Wayne; Skalli, Omar

2012-04-01

The intermediate filament protein synemin is present in astrocyte progenitors and glioblastoma cells but not in mature astrocytes. Here we demonstrate a role for synemin in enhancing glioblastoma cell proliferation and clonogenic survival, as synemin RNA interference decreased both behaviors by inducing G1 arrest along with Rb hypophosphorylation and increased protein levels of the G1/S inhibitors p21(Cip1) and p27(Kip1). Akt involvement was demonstrated by decreased phosphorylation of its substrate, p21(Cip1), and reduced Akt catalytic activity and phosphorylation at essential activation sites. Synemin silencing, however, did not affect the activities of PDPK1 and mTOR complex 2, which directly phosphorylate Akt activation sites, but instead enhanced the activity of the major regulator of Akt dephosphorylation, protein phosphatase type 2A (PP2A). This was accompanied by changes in PP2A subcellular distribution resulting in increased physical interactions between PP2A and Akt, as shown by proximity ligation assays (PLAs). PLAs and immunoprecipitation experiments further revealed that synemin and PP2A form a protein complex. In addition, treatment of synemin-silenced cells with the PP2A inhibitor cantharidic acid resulted in proliferation and pAkt and pRb levels similar to those of controls. Collectively these results indicate that synemin positively regulates glioblastoma cell proliferation by helping sequester PP2A away from Akt, thereby favoring Akt activation.

JNK-Interacting Protein 3 Mediates the Retrograde Transport of Activated c-Jun N-Terminal Kinase and Lysosomes

PubMed Central

Drerup, Catherine M.; Nechiporuk, Alex V.

2013-01-01

Retrograde axonal transport requires an intricate interaction between the dynein motor and its cargo. What mediates this interaction is largely unknown. Using forward genetics and a novel in vivo imaging approach, we identified JNK-interacting protein 3 (Jip3) as a direct mediator of dynein-based retrograde transport of activated (phosphorylated) c-Jun N-terminal Kinase (JNK) and lysosomes. Zebrafish jip3 mutants (jip3nl7) displayed large axon terminal swellings that contained high levels of activated JNK and lysosomes, but not other retrograde cargos such as late endosomes and autophagosomes. Using in vivo analysis of axonal transport, we demonstrated that the terminal accumulations of activated JNK and lysosomes were due to a decreased frequency of retrograde movement of these cargos in jip3nl7, whereas anterograde transport was largely unaffected. Through rescue experiments with Jip3 engineered to lack the JNK binding domain and exogenous expression of constitutively active JNK, we further showed that loss of Jip3–JNK interaction underlies deficits in pJNK retrograde transport, which subsequently caused axon terminal swellings but not lysosome accumulation. Lysosome accumulation, rather, resulted from loss of lysosome association with dynein light intermediate chain (dynein accessory protein) in jip3nl7, as demonstrated by our co-transport analyses. Thus, our results demonstrate that Jip3 is necessary for the retrograde transport of two distinct cargos, active JNK and lysosomes. Furthermore, our data provide strong evidence that Jip3 in fact serves as an adapter protein linking these cargos to dynein. PMID:23468645

TRL Assessment of Solar Sail Technology Development Following the 20-Meter System Ground Demonstrator Hardware Testing

NASA Technical Reports Server (NTRS)

Young, Roy M.; Adams, Charles L.

2010-01-01

The NASA In-Space Propulsion Technology (ISPT) Projects Office sponsored two separate, independent solar sail system design and development demonstration activities during 2002-2005. ATK Space Systems of Goleta, CA was the prime contractor for one development team and L' Garde, Inc. of Tustin, CA was the prime contractor for the other development team. The goal of these activities was to advance the technology readiness level (TRL) of solar sail propulsion from 3 towards 6 by the year 2006. Component and subsystem fabrication and testing were completed successfully, including the ground deployment of 10-meter and 20-meter demonstration hardware systems under vacuum conditions. The deployment and structural testing of the 20-meter solar sail systems was conducted in the 30 meter diameter Space Power Facility thermal-vacuum chamber at NASA Glenn Plum Brook in April though August, 2005. This paper will present the results of the TRL assessment following the solar sail technology development activities associated with the design, development, analysis and testing of the 20-meter system ground demonstrators.

Long-Term Maintenance of Pharmacists' Inhaler Technique Demonstration Skills

PubMed Central

Armour, Carol L; Reddel, Helen K; Bosnic-Anticevich, Sinthia Z

2009-01-01

Objective To assess the effectiveness of a single educational intervention, followed by patient education training, in pharmacists retaining their inhaler technique skills. Methods A convenience sample of 31 pharmacists attended an educational workshop and their inhaler techniques were assessed. Those randomly assigned to the active group were trained to assess and teach correct Turbuhaler and Diskus inhaler techniques to patients and provided with patient education tools to use in their pharmacies during a 6-month study. Control pharmacists delivered standard care. All pharmacists were reassessed 2 years after initial training. Results Thirty-one pharmacists participated in the study. At the initial assessment, few pharmacists demonstrated correct technique (Turbuhaler:13%, Diskus:6%). All pharmacists in the active group demonstrated correct technique following training. Two years later, pharmacists in the active group demonstrated significantly better inhaler technique than pharmacists in the control group (p < 0.05) for Turbuhaler and Diskus (83% vs.11%; 75% vs.11%, respectively). Conclusion Providing community pharmacists with effective patient education tools and encouraging their involvement in educating patients may contribute to pharmacists maintaining their competence in correct inhaler technique long-term. PMID:19513170

VENOM VARIATION IN HEMOSTASIS OF THE SOUTHERN PACIFIC RATTLESNAKE (Crotalus oreganus helleri): ISOLATION OF HELLERASE

PubMed Central

Salazar, Ana Maria; Guerrero, Belsy; Cantu, Bruno; Cantu, Esteban; Rodríguez-Acosta, Alexis; Pérez, John C.; Galán, Jacob A.; Tao, Andy; Sánchez, Elda E.

2009-01-01

Envenomations by the Southern Pacific Rattlesnake (Crotalus oreganus helleri) are the most common snakebite accidents in southern California. Intraspecies venom variation may lead to unresponsiveness of antivenom therapy. Even in a known species, venom toxins are recognized as diverse in conformity with interpopulational, seasonal, ontogenetic and individual factors. Five venoms of individual C. o. helleri located in Riverside and San Bernardino counties of southern California were studied for their variation in their hemostasis activity. The results demonstrated that Riverside 2 and San Bernardino 1 venoms presented the highest lethal activity without hemorrhagic activity. In contrast, San Bernardino 2 and 3 venoms had the highest hemorrhagic and fibrinolytic activities with low lethal and coagulant activities. Riverside 1, Riverside 2 and San Bernardino 1 venoms presented a significant thrombin-like activity. San Bernardino 2 and 3 venoms presented an insignificant thrombin-like activity. In relation to the fibrinolytic activity, San Bernardino 3 venom was the most active on fibrin plates, which was in turn neutralized by metal chelating inhibitors. These results demonstrate the differences amongst C. o helleri venoms from close localities. A metalloproteinase, hellerase, was purified by anionic and cationic exchange chromatography from San Bernardino 3 venom. Hellerase exhibited the ability to break fibrin clots in vitro, which can be of biomedically importance in the treatment of heart attacks and strokes. PMID:18804187

6-Gingerol inhibits osteosarcoma cell proliferation through apoptosis and AMPK activation.

PubMed

Fan, Jingzhang; Yang, Xin; Bi, Zhenggang

2015-02-01

6-Gingerol, a major component of ginger, is demonstrated to possess a variety of pharmacological activities. Despite demonstration of its anti-cancer activity, the exact mechanism underlying the effects of 6-gingerol against sarcoma remains sketchy. In the present study, we investigated the anti-cancer effects of 6-gingerol on osteosarcoma cells. MTT assay was performed to determine cell viability. Phosphorylation and protein levels were determined by immunoblotting. Cell cycle was determined using flow cytometry. Quantitative polymerase chain reaction was employed to determine the changes in the messenger RNA (mRNA) expression of genes. Treatment with 6-gingerol resulted in a significant decrease in the viability of osteosarcoma cells in a dose-dependent fashion. In parallel, the number of cells arrested at the sub-G1 cell cycle phase was significantly increased. The results showed that 6-gingerol induced activation of caspase cascades and regulated cellular levels of Bcl2 and Bax. Moreover, 6-gingerol activated AMP-activated protein kinase (AMPK) signaling associated with the apoptotic pathways. Our findings suggest that 6-gingerol suppresses the growth of osteosarcoma cells. The anti-cancer activity is attributed to the activation of apoptotic signaling and the inhibition of anti-apoptotic signaling incorporating with 6-gingerol-induced AMPK activation. The study identifies a new molecular mechanism by which AMPK is involved in anti-cancer effects of 6-gingerol.

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Taos, NM, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the EPA arsenic removal technology demonstration project at the Town of Taos in New Mexico. The main objective of the project was to evaluate the effectiveness of Severn Trent Services’ (STS) SORB 33™ ad...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Richmond Elementary School in Susanville, CA Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at Richmond Elementary School in Susanville, CA. The objectives of the project were to evaluate: (1) the effectiveness of an Aquatic Treatme...

Arsenic Removal from Drinking Water by Iron Removal U.S. EPA Demonstration Project at Sabin, MN Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from January 30, 2006 to April 29, 2007 at the U.S. Environmental Protection Agency (EPA) Arsenic Removal Technology Demonstration site in Sabin, MN. The main objective of the project was to evaluate the eff...

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Hot Springs Mobile Home Park in Willard, Utah - Final Performance Evaluation Report

EPA Science Inventory

This report documents activities performed for and results obtained from the arsenic removal treatment technology demonstration project at the Hot Springs Mobile Home Park (HSMHP) in Willard, UT. The objectives of the project were to evaluate the effectiveness of Adsorbsia™ GTO™...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Queen Anne’s County, Maryland Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at the community of Prospect Bay at Grasonville in Queen Anne’s County, MD. The main objective of the project was to evaluate the effective...

Arsenic Removal from Drinking Water by Iron Removal and Adsorptive Media U.S. EPA Demonstration Project at Stewart, MN, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the one-year U.S. Environmental Protection Agency (EPA) arsenic removal technology demonstration project at the Stewart, MN facility. The main objective of the project was to evaluate the effectiveness ...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Wellman, TX, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project in the City of Wellman, TX. The main objective of the project was to evaluate the effectiveness of AdEdge Technologies’ AD-33 media in remo...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Webb Consolidated Independent School District in Bruni, TX - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at the Webb Consolidated Independent School District (Webb CISD) in Bruni, TX. The main objective of the project was to evaluate the effect...

Arsenic Removal from Drinking Water by Adsorptive Media EPA Demonstration Project at Golden Hills Community Services District in Tehachapi, CA Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at Golden Hills Community Services District (GHCSD) located in Tehachapi, CA. The objectives of the project were to evaluate (1) the effecti...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Nambe Pueblo, New Mexico - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from this arsenic removal treatment technology demonstration project at the Nambe Pueblo, New Mexico. The main objective of the project was to evaluate the effectiveness of AdEdge Technologies' AD-33 media i...

Arsenic Removal from Drinking Water by Coagulation/Filtration U.S. EPA Demonstration Project at Village of Pentwater, MI. Final performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at the Village of Pentwater, MI facility. The objectives of the project were to evaluate: (1) the effectiveness of Kinetico’s FM-260...

Arsenic Removal from Drinking Water by Coagulation/Filtration U.S. EPA Demonstration Project at Town of Felton, DE, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at the Town of Felton, DE. The objectives of the project were to evaluate: (1) the effectiveness of Kinetico’s FM-348-AS coagulation...

Arsenic Removal from Drinking Water by Coagulation/Filtration, U.S. EPA Demonstration Project at the City of Okanogan, WA - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at the City of Okanogan, WA facility. The objectives of the project were to evaluate: (1) the effectiveness of Filtronics’ FH-13 Ele...

Arsenic Removal from Drinking Water by Coagulation/Filtration U.S. EPA Demonstration Project at City of Three Forks, MT, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at the City of Three Forks, MT facility. The objectives of the project were to evaluate: 1) the effectiveness of Kinetico’s FM-248-A...

Arsenic Removal from Drinking Water by Coagulation/Filtration U.S. EPA Demonstration Project at Sandusky, MI. Six-Month Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the EPA arsenic removal technology demonstration project at the City of Sandusky, MI facility. The objectives of the project are to evaluate 1) the effectiveness of Siemen...

Music through the Skin--Simple Demonstration of Human Electrical Conductivity

ERIC Educational Resources Information Center

Vollmer, M.; Möllmann, K. P.

2016-01-01

The conduction of electricity is an important topic for any basic physics course. Issues of safety often results in teacher demonstration experiments in front of the class or in extremely simple though--for students--not really fascinating (not to say boring) hands on activities for everybody using 1.5 V batteries, cables and light bulbs etc. Here…

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Woodstock Middle School in Woodstock, CT - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed for and the results obtained from the arsenic removal treatment technology demonstration project at the Woodstock Middle School in Woodstock, CT. The objectives of the project were to evaluate the effectiveness of Adsorbsia™ GTO™ me...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Wellman, TX, Six-Month Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the arsenic removal treatment technology demonstration project in the City of Wellman, TX. The main objective of the project was to evaluate the effectiveness of AdEdge Technolog...

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Seely-Brown Village in Pomfret, CT - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed for and the results obtained from the arsenic removal treatment technology demonstration project at Seely-Brown Village in Pomfret, CT. The objectives of the project were to evaluate the effectiveness of ArsenXnp adsorption media in...

Arsenic Removal from Drinking Water by Iron Removal - U.S. EPA Demonstration Project at Northeastern Elementary School in Fountain City, IN - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at Northeastern Elementary School in Fountain City, IN. The main objective of the project was to evaluate the effectiveness of US Water Sys...

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Geneseo Hills Subdivision, in Geneseo, IL Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at the Geneseo Hills Subdivision in Geneseo, IL. The main objective of the project was to evaluate the effectiveness of AdEdge Technologies...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Alvin, TX, Six-Month Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the EPA arsenic removal technology demonstration project at the Oak Manor Municipal Utility District (MUD) facility at Alvin, TX. The main objective of the project is to evaluate...

Arsenic Removal from Drinking Water by Adsorptive Media, U.S. EPA Demonstration Project at LEADS Head Start Building in Buckeye Lake, OH - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at Licking Economic Action Development Study (LEADS) Head Start School in Buckeye Lake, Ohio. The objectives of the project were to evaluate...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA. U.S. EPA DEMONSTRATION PROJECT AT SOUTH TRUCKEE MEADOWS GENERAL IMPROVEMENT DISTRICT (STMIG), NV. INTERIM EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first 32 weeks of operation of an arsenic and antimony removal technology currently being demonstrated at the South Truckee Meadows General Improvement District (STMGID) in Washoe County, NV. ...

ARSENIC REMOVAL FROM DRINKING WATER BY IRON REMOVAL AND ADSORPTIVE MEDIA USEPA DEMONSTRATION PROJECT AT STEWART, MN. SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the EPA arsenic removal technology demonstration project at the Stewart, MN facility. The main objective of the project is to evaluate the effectiveness of Siemens¿ Type II AERALA...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA. EPA DEMONSTRATION PROJECT AT QUEEN ANNES COUNTY, MARYLAND SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the community of Prospect Bay at Grasonville in Queen Anne’s County, MD. The objectives of the project were to ev...

Arsenic Removal from Drinking Water by Iron Removal. U.S. EPA Demonstration Project at Sabin, MN. Six-Month Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the EPA arsenic removal technology demonstration project at the Sabin, MN. The main objective of the project is to evaluate the effectiveness of the Kinetico FM-248-AS ars...

Microbiological quality and other characteristics of refrigerated chicken meat in contact with cellulose acetate-based film incorporated with rosemary essential oil

PubMed Central

de Melo, Adriane Alexandre Machado; Geraldine, Robson Maia; Silveira, Miriam Fontes Araujo; Torres, Maria Célia Lopes; e Rezende, Cíntia Silva Minafra; Fernandes, Thiago Henrique; de Oliveira, Antonio Nonato

2012-01-01

Antimicrobial active packaging delays or inhibits microorganism growth in packed products, and it can be used in a variety of food systems. The objective of the present research was to develop packaging incorporated with natural antimicrobial agents (active film). The effects of the active film on the spoilage, pathogenic microorganism counts, pH and color of the refrigerated chicken breast cuts were analyzed. Cellulose acetate-based active films incorporating two concentrations (20% and 50%, v/w) of rosemary (Rosmarinus officinalis L.) essential oil were manufactured and placed in contact with the chicken breast cuts for six days. An analysis of variance and mean comparison tests (Tukey’s test, p<0.05) were performed on the results. The films that contained 20% essential oil and were intercalated with chicken breast samples did not demonstrate significant effects on the control of psychrotrophic or total coliform microorganisms during the storage period; however, the films incorporated with 50% essential oil demonstrated efficacy toward the control of coliforms during the storage of the samples (6 days, 2 ± 2ºC). The pH was related to the psychrotrophic microorganism count and was not influenced by the treatment. The color was not influenced by the time of storage or the treatment. The results demonstrate that active films incorporating 50% rosemary essential oil are effective at controlling certain microorganisms in chicken breast cuts. PMID:24031972

[The characteristics of chemical composition of content of unicameral bone cysts depending on their growth stage].

PubMed

Stogov, M V; Luneva, S N; Mitrofanov, A I; Tkachuk, E A

2012-11-01

The article deals with the results of study of chemical composition of solitary cysts and blood serum of 27 patients. The results demonstrated that qualitative composition of f content of unicameral bone cysts is identical to chemical composition of blood serum. The results of analysis of total proteolysis activity and acid phosphatase activity in content of cysts can be used as criteria to determine the stage of cyst growth and to evaluate the effectiveness of applied treatment.

Constitutive activation of CaMKKα signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle.

PubMed

Ferey, Jeremie L A; Brault, Jeffrey J; Smith, Cheryl A S; Witczak, Carol A

2014-10-15

Skeletal muscle loading/overload stimulates the Ca²⁺-activated, serine/threonine kinase Ca²⁺/calmodulin-dependent protein kinase kinase-α (CaMKKα); yet to date, no studies have examined whether CaMKKα regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKα signaling could stimulate muscle growth and if so whether CaMKKα is essential for this process. CaMKKα signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKα using in vivo electroporation. After 2 wk, constitutively active CaMKKα expression increased muscle weight (~10%) and protein content (~10%), demonstrating that activation of CaMKKα signaling can stimulate muscle growth. To determine if active CaMKKα expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [³H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKα increased protein synthesis ~60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKα is essential for growth, muscles from CaMKKα knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKα knockout mice exhibited greater growth (~15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr³⁸⁹; ~50%), demonstrating that CaMKKα is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKα signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle. Copyright © 2014 the American Physiological Society.

Constitutive activation of CaMKKα signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle

PubMed Central

Ferey, Jeremie L. A.; Brault, Jeffrey J.; Smith, Cheryl A. S.

2014-01-01

Skeletal muscle loading/overload stimulates the Ca2+-activated, serine/threonine kinase Ca2+/calmodulin-dependent protein kinase kinase-α (CaMKKα); yet to date, no studies have examined whether CaMKKα regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKα signaling could stimulate muscle growth and if so whether CaMKKα is essential for this process. CaMKKα signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKα using in vivo electroporation. After 2 wk, constitutively active CaMKKα expression increased muscle weight (∼10%) and protein content (∼10%), demonstrating that activation of CaMKKα signaling can stimulate muscle growth. To determine if active CaMKKα expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [3H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKα increased protein synthesis ∼60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKα is essential for growth, muscles from CaMKKα knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKα knockout mice exhibited greater growth (∼15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr389; ∼50%), demonstrating that CaMKKα is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKα signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle. PMID:25159322

Chiral Thioxanthones as Modulators of P-glycoprotein: Synthesis and Enantioselectivity Studies.

PubMed

Lopes, Ana; Martins, Eva; Silva, Renata; Pinto, Madalena M M; Remião, Fernando; Sousa, Emília; Fernandes, Carla

2018-03-10

Recently, thioxanthone derivatives were found to protect cells against toxic P-glycoprotein (P-gp) substrates, acting as potent inducers/activators of this efflux pump. The study of new P-gp chiral modulators produced from thioxanthone derivatives could clarify the enantioselectivity of this ABC transporter towards this new class of modulators. The aim of this study was to evaluate the P-gp modulatory ability of four enantiomeric pairs of new synthesized chiral aminated thioxanthones (ATxs) 1 - 8 , studying the influence of the stereochemistry on P-gp induction/ activation in cultured Caco-2 cells. The data displayed that all the tested compounds (at 20 μM) significantly decreased the intracellular accumulation of a P-gp fluorescent substrate (rhodamine 123) when incubated simultaneously for 60 min, demonstrating an increased activity of the efflux, when compared to control cells. Additionally, all of them except ATx 3 (+), caused similar results when the accumulation of the P-gp fluorescent substrate was evaluated after pre-incubating cells with the test compounds for 24 h, significantly reducing the rhodamine 123 intracellular accumulation as a result of a significant increase in P-gp activity. However, ATx 2 (-) was the only derivative that, after 24 h of incubation, significantly increased P-gp expression. These results demonstrated a significantly increased P-gp activity, even without an increase in P-gp expression. Therefore, ATxs 1 - 8 were shown to behave as P-gp activators. Furthermore, no significant differences were detected in the activity of the protein when comparing the enantiomeric pairs. Nevertheless, ATx 2 (-) modulates P-gp expression differently from its enantiomer, ATx 1 (+). These results disclosed new activators and inducers of P-gp and highlight the existence of enantioselectivity in the induction mechanism.

In Vitro Antimicrobial and Modulatory Activity of the Natural Products Silymarin and Silibinin

PubMed Central

Rakelly de Oliveira, Dayanne; Relison Tintino, Saulo; Morais Braga, Maria Flaviana Bezerra; Boligon, Aline Augusti; Linde Athayde, Margareth; Douglas Melo Coutinho, Henrique; de Menezes, Irwin Rose Alencar; Fachinetto, Roselei

2015-01-01

Silymarin is a standardized extract from the dried seeds of the milk thistle (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The aim of this study was to investigate the antibacterial and antifungal activity of silymarin and its major constituent (silibinin) against different microbial strains and their modulatory effect on drugs utilized in clinical practice. Silymarin demonstrated antimicrobial activity of little significance against the bacterial strains tested, with MIC (minimum inhibitory concentration) values of 512 µg/mL. Meanwhile, silibinin showed significant activity against Escherichia coli with a MIC of 64 µg/mL. The results for the antifungal activity of silymarin and silibinin demonstrated a MIC of 1024 µg/mL for all strains. Silymarin and silibinin appear to have promising potential, showing synergistic properties when combined with antibacterial drugs, which should prompt further studies along this line. PMID:25866771

New heterocyclic derivatives of benzimidazole with germicidal activity. IV--In vivo anticandida activity of 5-fluoro-2-(5'-nitro-2'-furyl) benzimidazole (F-O-NO2).

PubMed

Pedini, M; Bistocchi, G A; De Meo, G; Ricci, A; Jacquignon, P; Riccardi, C; Bastianini, L; Sposini, T

1987-07-01

We have studied the possible in vitro and in vivo antibacterial activity of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2). Our data demonstrate that F-O-NO2 is able to inhibit the in vitro growth of different mycetes and bacteria, including Candida albicans and Cryptococcus neoformans. We also tested the possible in vivo activity against Candida albicans. The results clearly show that treatment with F-O-NO2 is able to significantly augment the survival of all treated animals; in particular, when injected i.p. at the dose of 120 mg/kg, 30' or 1 hr after Candida albicans challenge, it givens a MST (Medium Survival Time) longer than 60 days. These data demonstrate that F-O-NO2 has antibacterial and antimycotic activity.

The Time-Course of Lexical Activation During Sentence Comprehension in People With Aphasia

PubMed Central

Ferrill, Michelle; Love, Tracy; Walenski, Matthew; Shapiro, Lewis P.

2012-01-01

Purpose To investigate the time-course of processing of lexical items in auditorily presented canonical (subject–verb–object) constructions in young, neurologically unimpaired control participants and participants with left-hemisphere damage and agrammatic aphasia. Method A cross modal picture priming (CMPP) paradigm was used to test 114 control participants and 8 participants with agrammatic aphasia for priming of a lexical item (direct object noun) immediately after it is initially encountered in the ongoing auditory stream and at 3 additional time points at 400-ms intervals. Results The control participants demonstrated immediate activation of the lexical item, followed by a rapid loss (decay). The participants with aphasia demonstrated delayed activation of the lexical item. Conclusion This evidence supports the hypothesis of a delay in lexical activation in people with agrammatic aphasia. The delay in lexical activation feeds syntactic processing too slowly, contributing to comprehension deficits in people with agrammatic aphasia. PMID:22355007

Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport.

PubMed

Liao, Zheng-Gen; Tang, Tao; Guan, Xue-Jing; Dong, Wei; Zhang, Jing; Zhao, Guo-Wei; Yang, Ming; Liang, Xin-Li

2016-11-24

P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the mechanism by which imperatorin promotes P-gp-mediated drug transport. We used molecular docking to predict the binding force between imperatorin and P-gp and the effect of imperatorin on P-gp activity. P-gp efflux activity and P-gp ATPase activity were measured using a rhodamine 123 (Rh-123) accumulation assay and a Pgp-Glo™ assay; respectively. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess cellular membrane fluidity in MDCK-MDR1 cells. Western blotting was used to analyze the effect of imperatorin on P-gp expression; and P-gp mRNA levels were assessed by qRT-PCR. Molecular docking results demonstrated that the binding force between imperatorin and P-gp was much weaker than the force between P-gp and verapamil (a P-gp substrate). Imperatorin activated P-gp ATPase activity; which had a role in the inhibition of P-gp activity. Imperatorin promoted Rh-123 accumulation in MDCK-MDR1 cells and decreased cellular membrane fluidity. Western blotting demonstrated that imperatorin inhibited P-gp expression; and qRT-PCR revealed that imperatorin down-regulated P-gp (MDR1) gene expression. Imperatorin decreased P-gp-mediated drug efflux by inhibiting P-gp activity and the expression of P-gp mRNA and protein. Our results suggest that imperatorin could down-regulate P-gp expression to overcome multidrug resistance in tumors.

The Activity of Antimicrobial Surfaces Varies by Testing Protocol Utilized

PubMed Central

Campos, Matias D.; Zucchi, Paola C.; Phung, Ann; Leonard, Steven N.; Hirsch, Elizabeth B.

2016-01-01

Background Contaminated hospital surfaces are an important source of nosocomial infections. A major obstacle in marketing antimicrobial surfaces is a lack of efficacy data based on standardized testing protocols. Aim We compared the efficacy of multiple testing protocols against several “antimicrobial” film surfaces. Methods Four clinical isolates were used: one Escherichia coli, one Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry methods (modified ISO 22196 and ASTM E2149), a “dried droplet”, and a “transfer” method were tested against two commercially available antimicrobial films, one film in development, an untreated control, and a positive (silver) control film. At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from film surfaces and enumerated. Results Compared to untreated films in all protocols, there were no significant differences in recovery on either commercial brand at 2 or 24 hours after inoculation. The silver surface demonstrated significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and time points with the exception of 2 hours in the ISO protocol and the transfer method. Using our novel droplet method, no differences between placebo and active surfaces were detected. The surface in development demonstrated variable activity depending on method, organism, and time point. The ISO demonstrated minimal activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml difference versus placebo). The ASTEM protocol exhibited significant differences in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates (10 fold decrease). Minimal activity was observed with this film in the transfer method. Conclusions Varying results between protocols suggested that efficacy of antimicrobial surfaces cannot be easily and reproducibly compared. Clinical use should be considered and further development of representative methods is needed. PMID:27494336

Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

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

Lee, Jeong Eun; Hanyang Biomedical Research Institute, Seoul; Park, Jae Hyeon

2012-09-01

Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity asmore » well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.« less

The HCV Non-Nucleoside Inhibitor Tegobuvir Utilizes a Novel Mechanism of Action to Inhibit NS5B Polymerase Function

PubMed Central

Hebner, Christy M.; Han, Bin; Brendza, Katherine M.; Nash, Michelle; Sulfab, Maisoun; Tian, Yang; Hung, Magdeleine; Fung, Wanchi; Vivian, Randall W.; Trenkle, James; Taylor, James; Bjornson, Kyla; Bondy, Steven; Liu, Xiaohong; Link, John; Neyts, Johan; Sakowicz, Roman; Zhong, Weidong; Tang, Hengli; Schmitz, Uli

2012-01-01

Tegobuvir (TGV) is a novel non-nucleoside inhibitor (NNI) of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with TGV results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel. Further analysis reveals that the aberrantly migrating NS5B species contains the inhibitor molecule. Formation of this complex does not require the presence of any other HCV proteins. The intensity of the aberrantly migrating NS5B species is strongly dependent on cellular glutathione levels as well as CYP 1A activity. Furthermore analysis of NS5B protein purified from a heterologous expression system treated with TGV by mass spectrometry suggests that TGV undergoes a CYP- mediated intracellular activation step and the resulting metabolite, after forming a glutathione conjugate, directly and specifically interacts with NS5B. Taken together, these data demonstrate that upon metabolic activation TGV is a specific, covalent inhibitor of the HCV NS5B polymerase and is mechanistically distinct from other classes of the non-nucleoside inhibitors (NNI) of the viral polymerase. PMID:22720059

The Antibacterial Activity of Date Syrup Polyphenols against S. aureus and E. coli

PubMed Central

Taleb, Hajer; Maddocks, Sarah E.; Morris, R. Keith; Kanekanian, Ara D.

2016-01-01

Plant-derived products such as date syrup (DS) have demonstrated antibacterial activity and can inhibit bacteria through numerous different mechanisms, which may be attributed to bioactive compounds including plant-derived phenolic molecules. DS is rich in polyphenols and this study hypothesized that DS polyphenols demonstrate inherent antimicrobial activity, which cause oxidative damage. This investigation revealed that DS has a high content of total polyphenols (605 mg/100 g), and is rich in tannins (357 mg/100 g), flavonoids (40.5 mg/100 g), and flavanols (31.7 mg/100 g) that are known potent antioxidants. Furthermore, DS, and polyphenols extracted from DS, the most abundant bioactive constituent of DS are bacteriostatic to both Gram positive and Gram negative Escherichia coli and Staphylococcus aureus, respectively. It has further been shown that the extracted polyphenols independently suppress the growth of bacteria at minimum inhibitory concentration (MIC) of 30 and 20 mg/mL for E. coli and S. aureus, and have observed that DS behaves as a prooxidant by generating hydrogen peroxide that mediates bacterial growth inhibition as a result of oxidative stress. At sub-lethal MIC concentrations DS demonstrated antioxidative activity by reducing hydrogen peroxide, and at lethal concentrations DS demonstrated prooxidant activity that inhibited the growth of E. coli and S. aureus. The high sugar content naturally present in DS did not significantly contribute to this effect. These findings highlight that DS’s antimicrobial activity is mediated through hydrogen peroxide generation in inducing oxidative stress in bacteria. PMID:26952177

Polarimetric SAR calibration experiment using active radar calibrators

NASA Astrophysics Data System (ADS)

Freeman, Anthony; Shen, Yuhsyen; Werner, Charles L.

1990-03-01

Active radar calibrators are used to derive both the amplitude and phase characteristics of a multichannel polarimetric SAR from the complex image data. Results are presented from an experiment carried out using the NASA/JPL DC-8 aircraft SAR over a calibration site at Goldstone, California. As part of the experiment, polarimetric active radar calibrators (PARCs) with adjustable polarization signatures were deployed. Experimental results demonstrate that the PARCs can be used to calibrate polarimetric SAR images successfully. Restrictions on the application of the PARC calibration procedure are discussed.

Polarimetric SAR calibration experiment using active radar calibrators

NASA Technical Reports Server (NTRS)

Freeman, Anthony; Shen, Yuhsyen; Werner, Charles L.

1990-01-01

Active radar calibrators are used to derive both the amplitude and phase characteristics of a multichannel polarimetric SAR from the complex image data. Results are presented from an experiment carried out using the NASA/JPL DC-8 aircraft SAR over a calibration site at Goldstone, California. As part of the experiment, polarimetric active radar calibrators (PARCs) with adjustable polarization signatures were deployed. Experimental results demonstrate that the PARCs can be used to calibrate polarimetric SAR images successfully. Restrictions on the application of the PARC calibration procedure are discussed.

Color Me Metamorphic.

ERIC Educational Resources Information Center

Birdd, Donald L.

1990-01-01

Described are five activities using crayons to demonstrate the rock cycle including weathering, erosion and sedimentation, and sedimentary, metamorphic, and igneous rock formation. Discussed are materials, procedures, and probable results. (CW)

Performance Enhancement of a Full-Scale Vertical Tail Model Equipped with Active Flow Control

NASA Technical Reports Server (NTRS)

Whalen, Edward A.; Lacy, Douglas; Lin, John C.; Andino, Marlyn Y.; Washburn, Anthony E.; Graff, Emilio; Wygnanski, Israel J.

2015-01-01

This paper describes wind tunnel test results from a joint NASA/Boeing research effort to advance active flow control (AFC) technology to enhance aerodynamic efficiency. A full-scale Boeing 757 vertical tail model equipped with sweeping jet actuators was tested at the National Full-Scale Aerodynamics Complex (NFAC) 40- by 80-Foot Wind Tunnel (40x80) at NASA Ames Research Center. The model was tested at a nominal airspeed of 100 knots and across rudder deflections and sideslip angles that covered the vertical tail flight envelope. A successful demonstration of AFC-enhanced vertical tail technology was achieved. A 31- actuator configuration significantly increased side force (by greater than 20%) at a maximum rudder deflection of 30deg. The successful demonstration of this application has cleared the way for a flight demonstration on the Boeing 757 ecoDemonstrator in 2015.

syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

PubMed Central

El-Hillal, O.; Kurosaki, T.; Yamamura, H.; Kinet, J.-P.; Scharenberg, A. M.

1997-01-01

Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well. PMID:9050880

Inquiry-based Laboratory Activities on Drugs Analysis for High School Chemistry Learning

NASA Astrophysics Data System (ADS)

Rahmawati, I.; Sholichin, H.; Arifin, M.

2017-09-01

Laboratory activity is an important part of chemistry learning, but cookbook instructions is still commonly used. However, the activity with that way do not improve students thinking skill, especially students creativity. This study aims to improve high school students creativity through inquiry-based laboratory on drugs analysis activity. Acid-base titration is used to be method for drugs analysis involving a color changing indicator. The following tools were used to assess the activity achievement: creative thinking test on acid base titration, creative attitude and action observation sheets, questionnaire of inquiry-based lab activities, and interviews. The results showed that the inquiry-based laboratory activity improving students creative thinking, creative attitude and creative action. The students reacted positively to this teaching strategy as demonstrated by results from questionnaire responses and interviews. This result is expected to help teachers to overcome the shortcomings in other laboratory learning.

Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging.

PubMed

Belliere, Julie; Martinez de Lizarrondo, Sara; Choudhury, Robin P; Quenault, Aurélien; Le Béhot, Audrey; Delage, Christine; Chauveau, Dominique; Schanstra, Joost P; Bascands, Jean-Loup; Vivien, Denis; Gauberti, Maxime

2015-01-01

Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity. In particular, we demonstrated that diabetes mellitus induces chronic endothelial cells activation in the kidney and heart. Moreover, aged mice presented activated endothelial cells in the kidneys and the cerebrovasculature. Interestingly, depending on the underlying condition, the temporospatial patterns of endothelial activation in the vascular beds of the cardiovascular system were different. These results demonstrate the feasibility of detecting silent endothelial activation occurring in conditions associated with high cardiovascular risk using molecular MRI.

Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging

PubMed Central

Belliere, Julie; Martinez de Lizarrondo, Sara; Choudhury, Robin P.; Quenault, Aurélien; Le Béhot, Audrey; Delage, Christine; Chauveau, Dominique; Schanstra, Joost P.; Bascands, Jean-Loup; Vivien, Denis; Gauberti, Maxime

2015-01-01

Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity. In particular, we demonstrated that diabetes mellitus induces chronic endothelial cells activation in the kidney and heart. Moreover, aged mice presented activated endothelial cells in the kidneys and the cerebrovasculature. Interestingly, depending on the underlying condition, the temporospatial patterns of endothelial activation in the vascular beds of the cardiovascular system were different. These results demonstrate the feasibility of detecting silent endothelial activation occurring in conditions associated with high cardiovascular risk using molecular MRI. PMID:26379785

Using the memory activation capture (MAC) procedure to investigate the temporal dynamics of hypothesis generation.

PubMed

Lange, Nicholas D; Buttaccio, Daniel R; Davelaar, Eddy J; Thomas, Rick P

2014-02-01

Research investigating top-down capture has demonstrated a coupling of working memory content with attention and eye movements. By capitalizing on this relationship, we have developed a novel methodology, called the memory activation capture (MAC) procedure, for measuring the dynamics of working memory content supporting complex cognitive tasks (e.g., decision making, problem solving). The MAC procedure employs briefly presented visual arrays containing task-relevant information at critical points in a task. By observing which items are preferentially fixated, we gain a measure of working memory content as the task evolves through time. The efficacy of the MAC procedure was demonstrated in a dynamic hypothesis generation task in which some of its advantages over existing methods for measuring changes in the contents of working memory over time are highlighted. In two experiments, the MAC procedure was able to detect the hypothesis that was retrieved and placed into working memory. Moreover, the results from Experiment 2 suggest a two-stage process following hypothesis retrieval, whereby the hypothesis undergoes a brief period of heightened activation before entering a lower activation state in which it is maintained for output. The results of both experiments are of additional general interest, as they represent the first demonstrations of top-down capture driven by participant-established WM content retrieved from long-term memory.

Protein Kinase D1 attenuates tumorigenesis in colon cancer by modulating β-catenin/T cell factor activity

PubMed Central

Sundram, Vasudha; Ganju, Aditya; Hughes, Joshua E.; Khan, Sheema; Chauhan, Subhash C.; Jaggi, Meena

2014-01-01

Over 80% of colon cancer development and progression is a result of the dysregulation of β-catenin signaling pathway. Herein, for the first time, we demonstrate that a serine-threonine kinase, Protein Kinase D1 (PKD1), modulates the functions of β-catenin to suppress colon cancer growth. Analysis of normal and colon cancer tissues reveals downregulation of PKD1 expression in advanced stages of colon cancer and its co-localization with β-catenin in the colon crypts. This PKD1 downregulation corresponds with the aberrant expression and nuclear localization of β-catenin. In-vitro investigation of the PKD1-β-catenin interaction in colon cancer cells reveal that PKD1 overexpression suppresses cell proliferation and clonogenic potential and enhances cell-cell aggregation. We demonstrate that PKD1 directly interacts with β-catenin and attenuates β-catenin transcriptional activity by decreasing nuclear β-catenin levels. Additionally, we show that inhibition of nuclear β-catenin transcriptional activity is predominantly influenced by nucleus targeted PKD1. This subcellular modulation of β-catenin results in enhanced membrane localization of β-catenin and thereby increases cell-cell adhesion. Studies in a xenograft mouse model indicate that PKD1 overexpression delayed tumor appearance, enhanced necrosis and lowered tumor hypoxia. Overall, our results demonstrate a putative tumor-suppressor function of PKD1 in colon tumorigenesis via modulation of β-catenin functions in cells. PMID:25149539

Rapid analysis of controlled substances using desorption electrospray ionization mass spectrometry.

PubMed

Rodriguez-Cruz, Sandra E

2006-01-01

The recently developed technique of desorption electrospray ionization (DESI) has been applied to the rapid analysis of controlled substances. Experiments have been performed using a commercial ThermoFinnigan LCQ Advantage MAX ion-trap mass spectrometer with limited modifications. Results from the ambient sampling of licit and illicit tablets demonstrate the ability of the DESI technique to detect the main active ingredient(s) or controlled substance(s), even in the presence of other higher-concentration components. Full-scan mass spectrometry data provide preliminary identification by molecular weight determination, while rapid analysis using the tandem mass spectrometry (MS/MS) mode provides fragmentation data which, when compared to the laboratory-generated ESI-MS/MS spectral library, provide structural information and final identification of the active ingredient(s). The consecutive analysis of tablets containing different active components indicates there is no cross-contamination or interference from tablet to tablet, demonstrating the reliability of the DESI technique for rapid sampling (one tablet/min or better). Active ingredients have been detected for tablets in which the active component represents less than 1% of the total tablet weight, demonstrating the sensitivity of the technique. The real-time sampling of cannabis plant material is also presented.

Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab.

PubMed

Velayudhan, Jyoti; Chen, Yuh-Feng; Rohrbach, Amanda; Pastula, Christina; Maher, Gwen; Thomas, Heather; Brown, Ryan; Born, Teresa L

2016-08-01

Due to the complex molecular structure and proprietary manufacturing processes of monoclonal antibodies (mAbs), differences in structure and function may be expected during development of biosimilar mAbs. Important regulatory requirements for approval of biosimilar products involve comprehensive assessments of any potential differences between proposed biosimilars and reference mAbs, including differences in all known mechanisms of action, using sensitive and relevant methods. Any identified structural differences should not result in differences in biofunctional or clinical activity. A comprehensive assessment comparing the Amgen biosimilar candidate ABP 501 with FDA-licensed adalimumab (adalimumab [US]) and EU-authorized adalimumab (adalimumab [EU]) was conducted to demonstrate similarity in biofunctional activity. The functional similarity assessment included testing of binding kinetics to soluble tumor necrosis factor α (TNFα) and relative binding to transmembrane TNFα. The neutralization of TNFα-induced caspase activation, TNFα- and lymphotoxin-α (LTα)-induced chemokine production, and cytotoxicity was also tested. Binding to Fc-gamma receptors FcγRIa, FcγRIIa (131H), FcγRIIIa (158V and 158F), and neonatal Fc receptor (FcRn) was compared with the reference mAbs, as was antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The data demonstrate that ABP 501 is similar to both adalimumab (US) and adalimumab (EU) with respect to evaluated biofunctional activities. Similarity in biofunctional activity is a critical component of the totality of evidence required for demonstration of biosimilarity. The functional similarity demonstrated for ABP 501 comprehensively assesses the known mechanisms of action of adalimumab, supporting the conclusion that ABP 501, adalimumab (US), and adalimumab (EU) are likely to be clinically similar.

Antifungal activity of medicinal plant extracts; preliminary screening studies.

PubMed

Webster, Duncan; Taschereau, Pierre; Belland, René J; Sand, Crystal; Rennie, Robert P

2008-01-04

In the setting of HIV and organ transplantation, opportunistic fungal infections have become a common cause of morbidity and mortality. Thus antifungal therapy is playing a greater role in health care. Traditional plants are a valuable source of novel antifungals. To assess in vitro antifungal activity of aqueous plant extracts. The minimum inhibitory concentrations were determined for each extract in the setting of human pathogenic fungal isolates. Plants were harvested and identification verified. Aqueous extracts were obtained and antifungal susceptibilities determined using serial dilutional extracts with a standardized microdilution broth methodology. Twenty-three fungal isolates were cultured and exposed to the plant extracts. Five known antifungals were used as positive controls. Results were read at 48 and 72 h. Of the 14 plants analyzed, Fragaria virginiana Duchesne, Epilobium angustifolium L. and Potentilla simplex Michx. demonstrated strong antifungal potential overall. Fragaria virginiana had some degree of activity against all of the fungal pathogens. Alnus viridis DC., Betula alleghaniensis Britt. and Solidago gigantea Ait. also demonstrated a significant degree of activity against many of the yeast isolates. Fragaria virginiana, Epilobium angustifolium and Potentilla simplex demonstrate promising antifungal potential.

Comparative Demonstration of Active and Semi-Passive In Situ Bioremediation Approaches for Perchlorate-Impacted Groundwater at Longhorn Army Ammunitions Plant

DTIC Science & Technology

2009-01-01

lactate, citric acid , or ethanol have been used in field applications. Biomass grows rapidly during the active phase when high concentrations of...6.7.4 Results of Oxidation Reduction Potential (ORP) Monitoring.............39 6.7.5 Results of Volatile Fatty Acids (VFA) Analysis...trinitrotoluene USEPA U.S. Environmental Protection Agency VC vinyl chloride VFA volatile fatty acid VOC volatile organic compounds Technical

Knowledge representation into Ada parallel processing

NASA Technical Reports Server (NTRS)

Masotto, Tom; Babikyan, Carol; Harper, Richard

1990-01-01

The Knowledge Representation into Ada Parallel Processing project is a joint NASA and Air Force funded project to demonstrate the execution of intelligent systems in Ada on the Charles Stark Draper Laboratory fault-tolerant parallel processor (FTPP). Two applications were demonstrated - a portion of the adaptive tactical navigator and a real time controller. Both systems are implemented as Activation Framework Objects on the Activation Framework intelligent scheduling mechanism developed by Worcester Polytechnic Institute. The implementations, results of performance analyses showing speedup due to parallelism and initial efficiency improvements are detailed and further areas for performance improvements are suggested.

Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats.

PubMed

Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G

2013-05-01

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect.

Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats

PubMed Central

Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G.

2012-01-01

Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect. PMID:22692938

Physical activity is associated with reduced risk of esophageal cancer, particularly esophageal adenocarcinoma: a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Physical activity has been inversely associated with risk of several cancers. We performed a systematic review and meta-analysis to evaluate the association between physical activity and risk of esophageal cancer (esophageal adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). Methods We conducted a comprehensive search of bibliographic databases and conference proceedings from inception through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Results The analysis included 9 studies (4 cohort, 5 case–control) reporting 1,871 cases of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that the risk of esophageal cancer was 29% lower among the most physically active compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89), with moderate heterogeneity (I2 = 47%). On histology-specific analysis, physical activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2 = 0%). There were only 3 studies reporting the association between physical activity and risk of ESCC with conflicting results, and the meta-analysis demonstrated a null association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across study design, geographic location and study quality, with a non-significant trend towards a dose–response relationship. Conclusions Meta-analysis of published observational studies indicates that physical activity may be associated with reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of EAC. PMID:24886123

In-vivo extravasation induces the expression of interleukin 1 receptor type 1 in human neutrophils

PubMed Central

Paulsson, J M; Moshfegh, A; Dadfar, E; Held, C; Jacobson, S H; Lundahl, J

2012-01-01

In order to address neutrophil activation during inflammation we assessed the expression of interleukin 1 receptor type 1 (IL-1R1) following in-vivo extravasation. Extravasated neutrophils were collected from 11 healthy study subjects by a skin chamber technique and compared to neutrophils in peripheral blood. Expression of IL-1R1 was assessed by microarray, quantitative polymerase chain reaction (qPCR), Western blot, flow cytometry, enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy (iEM). IL-1R1 was induced following extravasation, demonstrated by both gene array and qPCR. Western blot demonstrated an increased expression of IL-1R1 in extravasated leucocytes. This was confirmed further in neutrophils by flow cytometry and iEM that also demonstrated an increased intracellular pool of IL-1R1 that could be mobilized by N-formyl-methionine-leucine-phenylalanine (fMLP). Stimulation of peripheral neutrophils with IL-1 resulted in transcription of NFκB and a number of downstream chemokines and the corresponding chemokines were also induced following in-vivo extravasation. The present results demonstrate that IL-1R1 is induced following extravasation and exists on the neutrophil surface, as well as in a mobile intracellular pool. Furthermore, neutrophils express functional IL-1R1 as demonstrated by the induction of chemokines following IL-1 stimulation. The results indicate a potential role for IL-1 in the activation of neutrophils at inflammatory sites. PMID:22385245

Nucleolin inhibitor GroA triggers reduction in epidermal growth factor receptor activation: Pharmacological implication for glial scarring after spinal cord injury.

PubMed

Goldshmit, Yona; Schokoroy Trangle, Sari; Afergan, Fabian; Iram, Tal; Pinkas-Kramarski, Ronit

2016-09-01

Glial scarring, formed by reactive astrocytes, is one of the major impediments for regeneration after spinal cord injury (SCI). Reactive astrocytes become hypertrophic, proliferate and secrete chondroitin sulphate proteoglycans into the extracellular matrix (ECM). Many studies have demonstrated that epidermal growth factor receptors (EGFR) can mediate astrocyte reactivity after neurotrauma. Previously we showed that there is crosstalk between nucleolin and EGFR that leads to increased EGFR activation followed by increased cell proliferation. Treatment with the nucleolin inhibitor GroA (AS1411) prevented these effects in vitro and in vivo. In this study, we hypothesized that similar interactions may mediate astrogliosis after SCI. Our results demonstrate that nucleolin and EGFR interaction may play a pivotal role in mediating astrocyte proliferation and reactivity after SCI. Moreover, we demonstrate that treatment with GroA reduces EGFR activation, astrocyte proliferation and chondroitin sulphate proteoglycans secretion, therefore promoting axonal regeneration and sprouting into the lesion site. Our results identify, for the first time, a role for the interaction between nucleolin and EGFR in astrocytes after SCI, indicating that nucleolin inhibitor GroA may be used as a novel treatment after neurotrauma. A major barrier for axonal regeneration after spinal cord injury is glial scar created by reactive and proliferating astrocytes. EGFR mediate astrocyte reactivity. We showed that inhibition of nucleolin by GroA, reduces EGFR activation, which results in attenuation of astrocyte reactivity and proliferation in vivo and in vitro. EGFR, epidermal growth factor receptor. © 2016 International Society for Neurochemistry.

Research and Teaching: A Comparison of Long-Term Knowledge Retention between Two Teaching Approaches

ERIC Educational Resources Information Center

Lysne, Steven J.; Miller, Brant G.

2017-01-01

Active instructional approaches have been demonstrated to result in greater student achievement, prompting institutions to transition to more active learning environments. However, little work has been conducted to specifically measure the retention of knowledge gained. The purpose of the research presented here was to test assumptions regarding…

Simple Research Paradigm for Demonstrating Subliminal Pschodynamic Activation: Effects of Oedipal Stimuli on Dart-Throwing Accuracy in College Males

ERIC Educational Resources Information Center

Silverman, Lloyd H.; And Others

1978-01-01

Four experiments were carried out in which "subliminal psychodynamic activation" effects, used for studying the relationship between psychopathology and unconscious conflict, were sought out from male college students. Results were discussed for their bearing on subliminal research and research in personality. (Editor/RK)

Circle Time Revisited: How Do Preschool Classrooms Use This Part of the Day?

ERIC Educational Resources Information Center

Bustamante, Andres S.; Hindman, Annemarie H.; Champagne, Carly R.; Wasik, Barbara A.

2018-01-01

Circle time is a near universally used preschool activity; however, little research has explored its nature, content, and quality. This study examined activity types, teacher and child talk, child engagement, and classroom quality in a sample of public preschool classrooms in an urban, high-poverty school district. Results demonstrated that…

Exercise and Diet in Obesity Treatment: An Integrative System Dynamics Perspective.

ERIC Educational Resources Information Center

Abdel-Hamid, Tarek K.

2003-01-01

Examined the utility of System Dynamics modeling as a vehicle for controlled experimentation to study and gain insight into the impacts of physical activity and diet on body weight and composition. Results underscored the significant interaction effects between physical activity, diet, and body composition and demonstrated the utility of…

Materials characterization activities for %E2%80%9CTake Our Sons&Daughters to Work Day%E2%80%9D 2013.

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

Mowry, Curtis Dale; Pimentel, Adam S.; Sparks, Elizabeth Schares

We created interactive demonstration activities for Take Our Daughters&Sons to Work Day (TODSTWD) 2013 in order to promote general interest in chemistry and also generate awareness of the type of work our laboratories can perform. %E2%80%9CCurious about Mars Rover Curiosity?%E2%80%9D performed an elemental analysis on rocks brought to our lab using the same technique utilized on the planet Mars by the NASA robotic explorer Curiosity. %E2%80%9CFood is Chemistry?%E2%80%9D utilized a mass spectrometer to measure, in seconds, each participant's breath in order to identify the food item consumed for the activity. A total of over 130 children participated in these activitiesmore » over a 3 hour block, and feedback was positive. This document reports the materials (including handouts), experimental procedures, and lessons learned so that future demonstrations can benefit from the baseline work performed. We also present example results used to prepare the Food activity and example results collected during the Curiosity demo.« less

A bioactive sesquiterpene from Bixa orellana.

PubMed

Raga, Dennis D; Espiritu, Rafael A; Shen, Chien-Chang; Ragasa, Consolacion Y

2011-01-01

A dichloromethane extract of the air-dried leaves of Bixa orellana afforded ishwarane 1, phytol 2, polyprenol 3, and a mixture of stigmasterol 4a and sitosterol 4b by silica gel chromatography. The structure of 1 was elucidated by extensive 1D and 2D NMR spectroscopy. Compound 1 at three doses (25, 50, and 100 mg/kg BW) was tested for prophylactic, gastrointestinal motility, analgesic, hypoglycemic, and antimicrobial potentials. Results of the prophylactic assay demonstrated the anti-toxic property of 1 at 100 mg/kg BW. A 50 mg/kg BW dose of 1 resulted in a more propulsive movement of the gastrointestinal tract (88.38 ± 13.59%) compared to the negative control (78.47 ± 10.61%). Tail flick and acetic acid writhing tests indicated that 100 mg/kg BW 1 had minimal analgesic activity. Compound 1 demonstrated no hypoglycemic potential on the animals tested. Compound 1 exhibited moderate antifungal activity against C. albicans, low activity against T. mentagrophytes, and low antibacterial activity against E. coli, S. aureus, and P. aeruginosa. It was inactive against B. subtilis and A. niger.

The effects of sesquiterpenes-rich extract of Alpinia oxyphylla Miq. on amyloid-β-induced cognitive impairment and neuronal abnormalities in the cortex and hippocampus of mice.

PubMed

Shi, Shao-Huai; Zhao, Xu; Liu, Bing; Li, Huan; Liu, Ai-Jing; Wu, Bo; Bi, Kai-Shun; Jia, Ying

2014-01-01

As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Aβ(1-42) and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-β (Aβ), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions.

The Effects of Sesquiterpenes-Rich Extract of Alpinia oxyphylla Miq. on Amyloid-β-Induced Cognitive Impairment and Neuronal Abnormalities in the Cortex and Hippocampus of Mice

PubMed Central

Shi, Shao-Huai; Zhao, Xu; Liu, Bing; Li, Huan; Liu, Ai-Jing; Wu, Bo; Bi, Kai-Shun

2014-01-01

As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Aβ 1−42 and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-β (Aβ), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions. PMID:25180067

Enhanced Photocatalytic Activity of Diamond Thin Films Using Embedded Ag Nanoparticles.

PubMed

Li, Shuo; Bandy, Jason A; Hamers, Robert J

2018-02-14

Silver nanoparticles embedded into the diamond thin films enhance the optical absorption and the photocatalytic activity toward the solvated electron-initiated reduction of N 2 to NH 3 in water. Here, we demonstrate the formation of diamond films with embedded Ag nanoparticles <100 nm in diameter. Cross-sectional scanning electron microscopy (SEM), energy-dependent SEM, and energy-dispersive X-ray analysis demonstrate the formation of encapsulated nanoparticles. Optical absorption measurements in the visible and ultraviolet region show that the resulting films exhibit plasmonic resonances in the visible and near-ultraviolet region. Measurements of photocatalytic activity using supraband gap (λ < 225 nm) and sub-band gap (λ > 225 nm) excitation show significantly enhanced ability to convert N 2 to NH 3 . Incorporation of Ag nanoparticles induces a nearly 5-fold increase in activity using a sub-band gap excitation with λ > 225 nm. Our results suggest that internal photoemission, in which electrons are excited from Ag into diamond's conduction band, is an important process that extends the wavelength region beyond diamond's band gap. Other factors, including Ag-induced optical scattering and formation of graphitic impurities are also discussed.

Resveratrol relieves Angiostrongylus cantonensis - Induced meningoencephalitis by activating sirtuin-1.

PubMed

Chen, An-Chih; Shyu, Ling-Yuh; Hsin, Yue-Loong; Chen, Ke-Min; Lai, Shih-Chan

2017-09-01

Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice. Moreover, resveratrol treatment significantly reduced eosinophil counts, p65, Interferon-γ, interleukin (IL)-5, IL-33, and tumor necrosis factor-α levels, matrix metalloproteinase-9 activity, claudin-5 degradation, and blood-brain barrier permeability. By contrast, the anti-inflammatory factor IL-10 was significantly increased in resveratrol-treated mice. Resveratrol treatment was partially beneficial in controlling the pathological processes of angiostrongyliasis meningoencephalitis. The results demonstrate the neuroprotective and anti-inflammatory effects of resveratrol against Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis in mice. Treatment with sirtuin-1 agonist was given within a therapeutic window after A. cantonensis infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Flow-induced phase separation of active particles is controlled by boundary conditions.

PubMed

Thutupalli, Shashi; Geyer, Delphine; Singh, Rajesh; Adhikari, Ronojoy; Stone, Howard A

2018-05-22

Active particles, including swimming microorganisms, autophoretic colloids, and droplets, are known to self-organize into ordered structures at fluid-solid boundaries. The entrainment of particles in the attractive parts of their spontaneous flows has been postulated as a possible mechanism underlying this phenomenon. Here, combining experiments, theory, and numerical simulations, we demonstrate the validity of this flow-induced ordering mechanism in a suspension of active emulsion droplets. We show that the mechanism can be controlled, with a variety of resultant ordered structures, by simply altering hydrodynamic boundary conditions. Thus, for flow in Hele-Shaw cells, metastable lines or stable traveling bands can be obtained by varying the cell height. Similarly, for flow bounded by a plane, dynamic crystallites are formed. At a no-slip wall, the crystallites are characterized by a continuous out-of-plane flux of particles that circulate and re-enter at the crystallite edges, thereby stabilizing them. At an interface where the tangential stress vanishes, the crystallites are strictly 2D, with no out-of-plane flux. We rationalize these experimental results by calculating, in each case, the slow viscous flow produced by the droplets and the long-ranged, many-body active forces and torques between them. The results of numerical simulations of motion under the action of the active forces and torques are in excellent agreement with experiments. Our work elucidates the mechanism of flow-induced phase separation in active fluids, particularly active colloidal suspensions, and demonstrates its control by boundaries, suggesting routes to geometric and topological phenomena in an active matter.

Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia

PubMed Central

Cohen, Taylor S.; Prince, Alice S.

2013-01-01

The respiratory tract is exceptionally well defended against infection from inhaled bacteria, with multiple proinflammatory signaling cascades recruiting phagocytes to clear airway pathogens. However, organisms that efficiently activate damaging innate immune responses, such as those mediated by the inflammasome and caspase-1, may cause pulmonary damage and interfere with bacterial clearance. The extracellular, opportunistic pathogen Pseudomonas aeruginosa expresses not only pathogen-associated molecular patterns that activate NF-κB signaling in epithelial and immune cells, but also flagella that activate the NLRC4 inflammasome. We demonstrate that induction of inflammasome signaling, ascribed primarily to the alveolar macrophage, impaired P. aeruginosa clearance and was associated with increased apoptosis/pyroptosis and mortality in a murine model of acute pneumonia. Strategies that limited inflammasome activation, including infection by fliC mutants, depletion of macrophages, deletion of NLRC4, reduction of IL-1β and IL-18 production, inhibition of caspase-1, and inhibition of downstream signaling in IL-1R– or IL-18R–null mice, all resulted in enhanced bacterial clearance and diminished pathology. These results demonstrate that the inflammasome provides a potential target to limit the pathological consequences of acute P. aeruginosa pulmonary infection. PMID:23478406

In Situ Observation of Chymotrypsin Catalytic Activity Change Actuated by Nonheating Low-Frequency Magnetic Field.

PubMed

Efremova, Maria V; Veselov, Maxim M; Barulin, Alexander V; Gribanovsky, Sergey L; Le-Deygen, Irina M; Uporov, Igor V; Kudryashova, Elena V; Sokolsky-Papkov, Marina; Majouga, Alexander G; Golovin, Yuri I; Kabanov, Alexander V; Klyachko, Natalia L

2018-04-24

Magnetomechanical modulation of biochemical processes is a promising instrument for bioengineering and nanomedicine. This work demonstrates two approaches to control activity of an enzyme, α-chymotrypsin immobilized on the surface of gold-coated magnetite magnetic nanoparticles (GM-MNPs) using a nonheating low-frequency magnetic field (LF MF). The measurement of the enzyme reaction rate was carried out in situ during exposure to the magnetic field. The first approach involves α-chymotrypsin-GM-MNPs conjugates, in which the enzyme undergoes mechanical deformations with the reorientation of the MNPs under LF MF (16-410 Hz frequency, 88 mT flux density). Such mechanical deformations result in conformational changes in α-chymotrypsin structure, as confirmed by infrared spectroscopy and molecular modeling, and lead to a 63% decrease of enzyme initial activity. The second approach involves an α-chymotrypsin-GM-MNPs/trypsin inhibitor-GM-MNPs complex, in which the activity of the enzyme is partially inhibited. In this case the reorientation of MNPs in the field leads to disruption of the enzyme-inhibitor complex and an almost 2-fold increase of enzyme activity. The results further demonstrate the utility of magnetomechanical actuation at the nanoscale for the remote modulation of biochemical reactions.

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.

Testing of resveratrol microemulsion photostability and protective effect against UV induced oxidative stress.

PubMed

Juškaitė, Vaida; Ramanauskienė, Kristina; Briedis, Vitalis

2017-06-27

Resveratrol is well known for its antioxidant activity and susceptibility to ultraviolet radiation. Development of formulations providing improved stability and relevant drug delivery of resveratrol is still a challenging task. The aim of this study was to determine protective characteristics of formulated microemulsions by evaluating photoisomerization of resveratrol and to investigate the effects of resveratrol on human keratinocyte cells under oxidative stress caused by ultraviolet radiation. Incorporation of resveratrol into microemulsions resulted in increased photostability of active compounds and the results demonstrated that photodegradation of resveratrol was significantly delayed. Results of biopharmaceutical evaluation in vitro demonstrated that up to 60 % of resveratrol was released from microemulsions within 6 hours under a constant release rate profile. In vivo biological testing confirmed the ability of resveratrol to protect cells from oxidative stress and to increase cell viability. It was concluded that microemulsions might be considered in the development of UV light sensitive compounds.

The effects of fitness on the aging process.

PubMed

Vopat, Bryan G; Klinge, Stephen A; McClure, Philip K; Fadale, Paul D

2014-09-01

Decades of research support the fact that much age-related deterioration is the result of the effects of sedentary lifestyles and the development of medical conditions rather than of aging itself. Elite older athletes, who demonstrate enhanced performance compared with historic cohorts and even some younger peers, are models of this paradigm. Many non-elite middle-aged adults and older adults continue to remain increasingly active throughout middle age and beyond. A continually growing body of basic science and clinical evidence demonstrates how active persons modulate physical decline through training. An updated understanding of how active adults defy age helps orthopaedic surgeons not only manage their patients' performance but also improve their lives. A large segment of sedentary older adults will benefit from counseling that encourages the pursuit of more active and healthier lifestyles. Copyright 2014 by the American Academy of Orthopaedic Surgeons.

A DEMETER-like DNA demethylase governs tomato fruit ripening

PubMed Central

Liu, Ruie; How-Kit, Alexandre; Stammitti, Linda; Teyssier, Emeline; Rolin, Dominique; Mortain-Bertrand, Anne; Halle, Stefanie; Liu, Mingchun; Kong, Junhua; Wu, Chaoqun; Degraeve-Guibault, Charlotte; Chapman, Natalie H.; Maucourt, Mickael; Hodgman, T. Charlie; Tost, Jörg; Bouzayen, Mondher; Hong, Yiguo; Seymour, Graham B.; Giovannoni, James J.; Gallusci, Philippe

2015-01-01

In plants, genomic DNA methylation which contributes to development and stress responses can be actively removed by DEMETER-like DNA demethylases (DMLs). Indeed, in Arabidopsis DMLs are important for maternal imprinting and endosperm demethylation, but only a few studies demonstrate the developmental roles of active DNA demethylation conclusively in this plant. Here, we show a direct cause and effect relationship between active DNA demethylation mainly mediated by the tomato DML, SlDML2, and fruit ripening— an important developmental process unique to plants. RNAi SlDML2 knockdown results in ripening inhibition via hypermethylation and repression of the expression of genes encoding ripening transcription factors and rate-limiting enzymes of key biochemical processes such as carotenoid synthesis. Our data demonstrate that active DNA demethylation is central to the control of ripening in tomato. PMID:26261318

Top-down enhancement and suppression of activity in category-selective extrastriate cortex from an act of reflective attention.

PubMed

Johnson, Matthew R; Johnson, Marcia K

2009-12-01

Recent research has demonstrated top-down attentional modulation of activity in extrastriate category-selective visual areas while stimuli are in view (perceptual attention) and after they are removed from view (reflective attention). Perceptual attention is capable of both enhancing and suppressing activity in category-selective areas relative to a passive viewing baseline. In this study, we demonstrate that a brief, simple act of reflective attention ("refreshing") is also capable of both enhancing and suppressing activity in some scene-selective areas (the parahippocampal place area [PPA]) but not others (refreshing resulted in enhancement but not in suppression in the middle occipital gyrus [MOG]). This suggests that different category-selective extrastriate areas preferring the same class of stimuli may contribute differentially to reflective processing of one's internal representations of such stimuli.

In vivo imaging of protease activity by Probody therapeutic activation

PubMed Central

Wong, Kenneth R.; Menendez, Elizabeth; Craik, Charles S.; Kavanaugh, W. Michael; Vasiljeva, Olga

2017-01-01

Probody™ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment. PMID:26546838

[Active ageing and quality of life--Results of a WHO demonstration project].

PubMed

von dem Knesebeck, O; David, K; Bill, P; Hikl, R

2006-04-01

Based on the Active Ageing Programme of the World Health Organization (WHO), a demonstration project was conducted in a city in North-Rhine Westphalia between October 2002 and December 2004. The aim of the study was to promote an active ageing process, to maintain autonomy and independence among older people, and thereby to promote health and quality of life. The target group included people aged 55 to 80 years. The aim was to include older persons in a critical period of life due to loss of partner within the last five years and people undergoing a status change due to retirement within the last two years. 344 participants were visited at home to assess their health and psychosocial situation and to identify opportunities for activities. Participants were supported in their efforts to realise the agreed-upon activities. In this article results of the external evaluation are presented. It is analysed whether quality of life according to the WHOQOL Bref improves among participants in the course of the project. Results of non-parametric tests show small differences in quality of life between the three waves of interviews (at the beginning of the project, after one year, at the end of the project). This holds true when only those participants are analysed who retired within the last two years. However, quality of life significantly improves among older persons who lost their partner within the last five years. In terms of implementation of the WHO Active Ageing Programme results suggest application of a risk group strategy.

Arsenic Removal from Drinking Water by Iron Removal U.S. EPA Demonstration Project at Vintage on the Ponds in Delavan, WI Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at Vintage on the Ponds in Delavan, WI. The objectives of the project were to evaluate: (1) the effectiveness of a Kinetico Macrolite® press...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA U.S. EPA DEMONSTRATION PROJECT AT CHATEAU ESTATES MOBILE HOME PARK IN SPRINGFIELD, OH. SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed for and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the Chateau Estates Mobile Home Park at Springfield, OH. The objectives of the project are to evaluate the ef...

ARSENIC REMOVAL FROM DRINKING WATER BY IRON REMOVAL USEPA DEMONSTRATION PROJECT AT BIG SAUK LAKE MOBILE HOME PARK IN SAUK CENTRE, MN. SIX MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the Big Sauk Lake Mobile Home Park (BSLMHP) in Sauk Centre, MN. The objectives of the project are to evaluate the...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA U.S. EPA DEMONSTRATION PROJECT AT SPRING BROOK MOBILE HOME PARK IN WALES, ME SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the Spring Brook Mobile Home Park in Wales, ME. The objectives of the project are to evaluate the effectiv...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Spring Brook Mobile Home Park in Wales, ME Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the arsenic removal treatment technology demonstration project at Spring Brook Mobile Home Park (SBMHP) in Wales, Maine. The objectives of the project were to evaluate: 1) the effectiveness of an arsenic...

ARSENIC REMOVAL FROM DRINKING WATER BY ADSORPTIVE MEDIA U.S. EPA DEMONSTRATION PROJECT AT CHATEAU ESTATES MOBILE HOME PARK IN SPRINGFIELD, OH. FINAL PERFORMANCE EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed for and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at the Chateau Estates Mobile Home Park at Springfield, OH. The objectives of the project are to evaluate the ef...

Arsenic Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at Covered Wells in Tohono O’odham Nation, AZ - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at Covered Wells in Tohono O’odham Nation, AZ. The main objective of the project was to evaluate the effectiveness of AdEdge Technologies’ ...

Arsenic Removal from Drinking Water by Adsorptive Media. U.S. EPA Demonstration Project at Oak Manor Municipal Utility District at Alvin, TX. Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained for the EPA arsenic removal technology demonstration project at the Oak Manor Municipal Utility District (MUD) facility in Alvin, TX. The objectives of the project were to evaluate 1) the effectiveness of a ...

Arsenic Removal from Drinking Water by Coagulation/Filtration - U.S. EPA Demonstration Project at Conneaut Lake Park in Conneaut Lake, PA - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the arsenic removal treatment technology demonstration project at Conneaut Lake Park (the Park) in Conneaut Lake, PA. The main objective of the project was to evaluate the effectiveness of AdEdge Techno...

ARSENIC REMOVAL FROM DRINKING WATER BY IRON REMOVAL. U.S. EPA DEMONSTRATION PROJECT AT VILLAGE ON THE PONDS IN DELAVAN, WI. SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed and the results obtained from the first six months of the arsenic removal treatment technology demonstration project at Vintage on the Ponds at Delavan, WI. The objectives of the project are to evaluate: (1) the effectiveness of Kine...

ARSENIC REMOVAL FROM DRINKING WATER BY POINT OF USE REVERSE OSMOSIS. EPA DEMONSTRATION PROJECT AT SUNSET RANCH DEVELOPMENT IN HOMEDALE, ID. SIX-MONTH EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first six months of the point of use arsenic removal treatment technology demonstration project at the Sunset Ranch Development in Homedale, ID. The objectives of the project are to evaluate t...

Arsenic Removal from Drinking Water by Oxidation/Filtration and Adsorptive Media, U.S. EPA Demonstration Project at Clinton Christian School in Goshen, IN - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed for and the results obtained from the arsenic removal treatment technology demonstration project at the Clinton Christian School in Goshen, IN. The objectives of the project were to evaluate the effectiveness of AdEdge Technologies’...

Seeing Green: Mere Exposure to Money Triggers a Business Decision Frame and Unethical Outcomes

ERIC Educational Resources Information Center

Kouchaki, Maryam; Smith-Crowe, Kristin; Brief, Arthur P.; Sousa, Carlos

2013-01-01

Can mere exposure to money corrupt? In four studies, we examined the likelihood of unethical outcomes when the construct of money was activated through the use of priming techniques. The results of Study 1 demonstrated that individuals primed with money were more likely to demonstrate unethical intentions than those in the control group. In Study…

Arsenic and Uranium Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Upper Bodfish in Lake Isabella, CA -Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the performance evaluation of an arsenic (As) and uranium (U) removal technology demonstrated at Upper Bodfish in Lake Isabella, CA. The objectives of the project are to evaluate: (1) the effecti...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Upper Bodfish in Lake Isabella, CA Interim Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first 10 months of system operation of an arsenic (As) and uranium (U) removal technology being demonstrated at Upper Bodfish in Lake Isabella, CA. The objectives of the project are to evalua...

Arsenic and Antimony Removal from Drinking Water by Adsorptive Media - U.S. EPA Demonstration Project at South Truckee Meadows General Improvement District (STMGID), NV, Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the operation of an arsenic and antimony removal technology demonstrated at the South Truckee Meadows General Improvement District (STMGID) in Washoe County, NV. The objectives of the project wer...

An integrated approach to demonstrating the ANR pathway of proanthocyanidin biosynthesis in plants.

PubMed

Peng, Qing-Zhong; Zhu, Yue; Liu, Zhong; Du, Ci; Li, Ke-Gang; Xie, De-Yu

2012-09-01

Proanthocyanidins (PAs) are oligomers or polymers of plant flavan-3-ols and are important to plant adaptation in extreme environmental conditions. The characterization of anthocyanidin reductase (ANR) and leucoanthocyanidin reductase (LAR) has demonstrated the different biogenesis of four stereo-configurations of flavan-3-ols. It is important to understand whether ANR and the ANR pathway widely occur in the plant kingdom. Here, we report an integrated approach to demonstrate the ANR pathway in plants. This includes different methods to extract native ANR from different tissues of eight angiosperm plants (Lotus corniculatus, Desmodium uncinatum, Medicago sativa, Hordeum vulgare, Vitis vinifera, Vitis bellula, Parthenocissus heterophylla, and Cerasus serrulata) and one fern plant (Dryopteris pycnopteroides), a general enzymatic analysis approach to demonstrate the ANR activity, high-performance liquid chromatography-based fingerprinting to demonstrate (-)-epicatechin and other flavan-3-ol molecules, and phytochemical analysis of PAs. Results demonstrate that in addition to leaves of M. sativa, tissues of other eight plants contain an active ANR pathway. Particularly, the leaves, flowers and pods of D. uncinatum, which is a model plant to study LAR and the LAR pathways, are demonstrated to express an active ANR pathway. This finding suggests that the ANR pathway involves PA biosynthesis in D. uncinatum. In addition, a sequence BLAST analysis reveals that ANR homologs have been sequenced in plants from both gymnosperms and angiosperms. These data show that the ANR pathway to PA biosynthesis occurs in both seed and seedless vascular plants.

Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

PubMed

Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

2002-12-30

Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.

Pickpocket1 Is an Ionotropic Molecular Sensory Transducer*

PubMed Central

Boiko, Nina; Kucher, Volodymyr; Stockand, James D.; Eaton, Benjamin A.

2012-01-01

The molecular transformation of an external stimulus into changes in sensory neuron activity is incompletely described. Although a number of molecules have been identified that can respond to stimuli, evidence that these molecules can transduce stimulation into useful neural activity is lacking. Here we demonstrate that pickpocket1 (ppk1), a Drosophila homolog of mammalian Degenerin/epithelial sodium channels, encodes an acid-sensing sodium channel that conducts a transient depolarizing current in multidendritic sensory neurons of Drosophila melanogaster. Stimulation of Ppk1 is sufficient to bring these sensory neurons to threshold, eliciting a burst of action potentials. The transient nature of the neural activity produced by Ppk1 activation is the result of Ppk1 channel gating properties. This model is supported by the observation of enhanced bursting activity in neurons expressing a gain of function ppk1 mutant harboring the degenerin mutation. These findings demonstrate that Ppk1 can function as an ionotropic molecular sensory transducer capable of transforming the perception of a stimulus into phasic neuronal activity in sensory neurons. PMID:23033486

Discovery of core-structurally novel PTP1B inhibitors with specific selectivity containing oxindole-fused spirotetrahydrofurochroman by one-pot reaction.

PubMed

Dong, Suzhen; Lei, Yubing; Jia, Shikun; Gao, Lixin; Li, Jia; Zhu, Tong; Liu, Shunying; Hu, Wenhao

2017-02-15

Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an ideal target for treatment of type II diabetes and obesity. However, no druggable PTP1B inhibitor has been established and there is still an urgent demand for the development of structurally novel PTPIB inhibitor. Herein, we reported core-structurally novel PTP1B inhibitors with low micromole-ranged inhibitory activity by one-pot reaction from simple starting materials. Further studies demonstrated some of these active compounds had a specific selectivity over other PTPs. The structure and activity relationship was also described. The best active and selective compound 5e inhibited PTP1B activity with an IC 50 of 4.53μM. Molecular docking analysis further demonstrated that compound 5e bound to the active pocket of PTP1B. The results might provide some insights for further development of new drugs for type II diabetes and obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?

PubMed

Anthony, R M; den Hertog, A L; van Soolingen, D

2018-03-08

A low pH was assumed to be required for the activity of pyrazinoic acid (the active form of pyrazinamide) against Mycobacterium tuberculosis, but recently activity has been demonstrated at neutral pH. Renewed interest in pyrazinamide has led to an increasing number of potential targets and the suspicion that pyrazinamide is a 'dirty drug'. However, it is our opinion that the recent demonstration that pyrazinoic acid is active against PanD provides an alternative explanation for the secret of pyrazinamide's unusual activity. In this article we propose that PanD is the primary target of pyrazinoic acid but expression of pyrazinoic acid susceptibility requires an intact stress response. As the mycobacterial stress response requires the interaction of a number of genes, disruption of any could result in an inability to enter the susceptible phenotype. We believe this model can explain most of the recent observations of the seemingly diverse spectrum of activity of pyrazinamide.

Knockdown of Ice-Binding Proteins in Brachypodium distachyon Demonstrates Their Role in Freeze Protection

PubMed Central

Bredow, Melissa; Vanderbeld, Barbara; Walker, Virginia K.

2016-01-01

Sub-zero temperatures pose a major threat to the survival of cold-climate perennials. Some of these freeze-tolerant plants produce ice-binding proteins (IBPs) that offer frost protection by restricting ice crystal growth and preventing expansion-induced lysis of the plasma membranes. Despite the extensive in vitro characterization of such proteins, the importance of IBPs in the freezing stress response has not been investigated. Using the freeze-tolerant grass and model crop, Brachypodium distachyon, we characterized putative IBPs (BdIRIs) and generated the first ‘IBP-knockdowns’. Seven IBP sequences were identified and expressed in Escherichia coli, with all of the recombinant proteins demonstrating moderate to high levels of ice-recrystallization inhibition (IRI) activity, low levels of thermal hysteresis (TH) activity (0.03−0.09°C at 1 mg/mL) and apparent adsorption to ice primary prism planes. Following plant cold acclimation, IBPs purified from wild-type B. distachyon cell lysates similarly showed high levels of IRI activity, hexagonal ice-shaping, and low levels of TH activity (0.15°C at 0.5 mg/mL total protein). The transfer of a microRNA construct to wild-type plants resulted in the attenuation of IBP activity. The resulting knockdown mutant plants had reduced ability to restrict ice-crystal growth and a 63% reduction in TH activity. Additionally, all transgenic lines were significantly more vulnerable to electrolyte leakage after freezing to −10°C, showing a 13−22% increase in released ions compared to wild-type. IBP-knockdown lines also demonstrated a significant decrease in viability following freezing to −8°C, with some lines showing only two-thirds the survival seen in control lines. These results underscore the vital role IBPs play in the development of a freeze-tolerant phenotype and suggests that expression of these proteins in frost-susceptible plants could be valuable for the production of more winter-hardy crops. PMID:27959937

Knockdown of Ice-Binding Proteins in Brachypodium distachyon Demonstrates Their Role in Freeze Protection.

PubMed

Bredow, Melissa; Vanderbeld, Barbara; Walker, Virginia K

2016-01-01

Sub-zero temperatures pose a major threat to the survival of cold-climate perennials. Some of these freeze-tolerant plants produce ice-binding proteins (IBPs) that offer frost protection by restricting ice crystal growth and preventing expansion-induced lysis of the plasma membranes. Despite the extensive in vitro characterization of such proteins, the importance of IBPs in the freezing stress response has not been investigated. Using the freeze-tolerant grass and model crop, Brachypodium distachyon, we characterized putative IBPs (BdIRIs) and generated the first 'IBP-knockdowns'. Seven IBP sequences were identified and expressed in Escherichia coli, with all of the recombinant proteins demonstrating moderate to high levels of ice-recrystallization inhibition (IRI) activity, low levels of thermal hysteresis (TH) activity (0.03-0.09°C at 1 mg/mL) and apparent adsorption to ice primary prism planes. Following plant cold acclimation, IBPs purified from wild-type B. distachyon cell lysates similarly showed high levels of IRI activity, hexagonal ice-shaping, and low levels of TH activity (0.15°C at 0.5 mg/mL total protein). The transfer of a microRNA construct to wild-type plants resulted in the attenuation of IBP activity. The resulting knockdown mutant plants had reduced ability to restrict ice-crystal growth and a 63% reduction in TH activity. Additionally, all transgenic lines were significantly more vulnerable to electrolyte leakage after freezing to -10°C, showing a 13-22% increase in released ions compared to wild-type. IBP-knockdown lines also demonstrated a significant decrease in viability following freezing to -8°C, with some lines showing only two-thirds the survival seen in control lines. These results underscore the vital role IBPs play in the development of a freeze-tolerant phenotype and suggests that expression of these proteins in frost-susceptible plants could be valuable for the production of more winter-hardy crops.

Active vibration damping of the Space Shuttle remote manipulator system

NASA Technical Reports Server (NTRS)

Scott, Michael A.; Gilbert, Michael G.; Demeo, Martha E.

1991-01-01

The feasibility of providing active damping augmentation of the Space Shuttle Remote Manipulator System (RMS) following normal payload handling operations is investigated. The approach used in the analysis is described, and the results for both linear and nonlinear performance analysis of candidate laws are presented, demonstrating that significant improvement in the RMS dynamic response can be achieved through active control using measured RMS tip acceleration data for feedback.

Effects of Breast Cancer Chemotherapy Agents on Brain Activity in Rats: Functional Imaging Studies

DTIC Science & Technology

2011-04-29

and in a small region of the striatum. Visual stimulation produced bilateral activation of the superior colliculus, lateral geniculate and a small...pattern was seen in the lateral geniculate . These results demonstrate the feasibility of using brain activation by parametric sensory stimulation as...both the right and left lateral geniculate functional ROIs (25% and 29%, respectively). There were smaller but not statistically significant decreases

Palladium-pyridyl catalytic films: a highly active and recyclable catalyst for hydrogenation of styrene under mild conditions.

PubMed

Gao, Shuiying; Li, Weijin; Cao, Rong

2015-03-01

Palladium-pyridyl catalytic films, (PdCl2/bpy)n, were created by alternating immersions of a substrate in PdCl2 and bpy (bpy=4, 4'-bipyridyl) solutions. The as-prepared (PdCl2/bpy)10 catalyst demonstrated a remarkable catalytic activity toward hydrogenation of styrene under mild conditions and the turnover frequency (TOF) is as high as 6944h(-1). Pd(II) ions of (PdCl2/bpy)n films are in situ reduced to Pd nanoparticles (NPs) during the hydrogenation of styrene process, which results in the catalytic activity of the films. The results of X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) further demonstrate that Pd(II) ions of (PdCl2/bpy)n films were gradually converted to Pd(0) states. The catalytic activity is related to bilayer numbers and the activity increases with the number of bilayers below 10 bilayers. The solid substrates coated with (PdCl2/bpy)n multilayer catalysts were easily removed from the reaction mixture without separation filtration. Moreover, (PdCl2/bpy)n catalysts were reused for 10 consecutive reactions without loss of activity. The present (PdCl2/bpy)n heterogeneous catalysts have the advantages of easy separation and good recyclability. Copyright © 2014 Elsevier Inc. All rights reserved.

Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity.

PubMed

Yao, Yongxue; Harrison, Kathleen A; Al-Hassani, Mohammed; Murphy, Robert C; Rezania, Samin; Konger, Raymond L; Travers, Jeffrey B

2012-03-16

To date, oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPCs play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein xeroderma pigmentosum type A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor ultraviolet B (UVB) radiation resulted in increased reactive oxygen species and PAF receptor (PAF-R) agonistic activity in comparison with gene-corrected cells. The UVB irradiation-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison with control mice. The increased UVB irradiation-mediated skin inflammation and TNF-α production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R-stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chain Ox-GPCs along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity.

Trivalent chromium activates Rac-1 and Src and induces switch in the cell death mode in human dermal fibroblasts.

PubMed

Rudolf, Emil; Cervinka, Miroslav

2009-08-10

In this study we examined interactions between human dermal fibroblasts and chromium acetate hydroxide originating from environmental waste sediments. We show that initially exposure of fibroblasts to Cr (III) induced membrane-dependent signaling including activation of Rac1 GTPase, Src and apoptosis signal-regulating kinase 1 (ASK-1) kinases leading to increased activities of p38 and particularly Jun N-terminal kinase (JNK) and subsequent activation of caspase-3. At later treatment intervals (48-96 h), caspase-3 activity became suppressed and markedly increased lactate dehydrogenase (LDH) release was observed. Further experiments demonstrated that LDH release occurred in the presence of increased oxidative stress, extensive DNA damage, overactivation of poly(ADP-ribose)polymerase-1 (PARP-1) and depletion of ATP. Using specific inhibitors it was demonstrated that oxidative stress along with PARP-1 activity are responsible for cell death mode switch and upon their inhibition caspase-3 activity could be restored. In conclusion, Cr (III) seems to induce a biphasic response in dermal fibroblasts, with initial apoptosis switched to necrosis via increased DNA damage and resulting PARP-1 activity.

Dynamic Modulation of Human Motor Activity When Observing Actions

PubMed Central

Press, Clare; Cook, Jennifer; Blakemore, Sarah-Jayne; Kilner, James

2012-01-01

Previous studies have demonstrated that when we observe somebody else executing an action many areas of our own motor systems are active. It has been argued that these motor activations are evidence that we motorically simulate observed actions; this motoric simulation may support various functions such as imitation and action understanding. However, whether motoric simulation is indeed the function of motor activations during action observation is controversial, due to inconsistency in findings. Previous studies have demonstrated dynamic modulations in motor activity when we execute actions. Therefore, if we do motorically simulate observed actions, our motor systems should also be modulated dynamically, and in a corresponding fashion, during action observation. Using magnetoencephalography, we recorded the cortical activity of human participants while they observed actions performed by another person. Here, we show that activity in the human motor system is indeed modulated dynamically during action observation. The finding that activity in the motor system is modulated dynamically when observing actions can explain why studies of action observation using functional magnetic resonance imaging have reported conflicting results, and is consistent with the hypothesis that we motorically simulate observed actions. PMID:21414901

Neural activation in the orbitofrontal cortex in response to male faces increases during the follicular phase

PubMed Central

Rupp, Heather A.; James, Thomas W.; Ketterson, Ellen D.; Sengelaub, Dale R.; Janssen, Erick; Heiman, Julia R.

2009-01-01

Women’s sexual interest changes with hormonal fluctuations across the menstrual cycle. It is unclear how hormones modify women’s sexual behavior and desire, but one possibility is that they alter women’s positive appraisals of stimuli and thus their sexual interest. Using 3 T fMRI, we measured neural activation in women at two time points in their menstrual cycle (late follicular, luteal) while they evaluated photos of men presented as potential sexual partners. Participants were ten heterosexual women aged 23–28 none of who was using hormonal contraceptives or in a committed relationship. In an event-related design, the women were presented with as series of photos of male faces and asked questions to assess their degree of sexual interest in the men depicted. Results demonstrate an overall effect of menstrual cycle phase on neural activation. During their follicular versus luteal phase, women demonstrated increased activation in the right medial orbitofrontal cortex (OFC), suggesting increased positive appraisal. Activation in the OFC was positively correlated with women’s estradiol to progesterone ratios. There were no areas that demonstrated increased activation during the luteal versus follicular phase. The observed increase in activation in the OFC during the follicular phase may reflect a hormonally mediated increase in appetitive motivation and may prime women towards increased sexual interest and behavior around ovulation. PMID:19306881

The cholinergic forebrain arousal system acts directly on the circadian pacemaker

PubMed Central

Yamakawa, Glenn R.; Basu, Priyoneel; Cortese, Filomeno; MacDonnell, Johanna; Whalley, Danica; Smith, Victoria M.

2016-01-01

Sleep and wake states are regulated by a variety of mechanisms. One such important system is the circadian clock, which provides temporal structure to sleep and wake. Conversely, changes in behavioral state, such as sleep deprivation (SD) or arousal, can phase shift the circadian clock. Here we demonstrate that the level of wakefulness is critical for this arousal resetting of the circadian clock. Specifically, drowsy animals with significant power in the 7- to 9-Hz band of their EEGs do not exhibit phase shifts in response to a mild SD procedure. We then show that treatments that both produce arousal and reset the phase of circadian clock activate (i.e., induce Fos expression in) the basal forebrain. Many of the activated cells are cholinergic. Using retrograde tract tracing, we demonstrate that cholinergic cells activated by these arousal procedures project to the circadian clock in the suprachiasmatic nuclei (SCN). We then demonstrate that arousal-induced phase shifts are blocked when animals are pretreated with atropine injections to the SCN, demonstrating that cholinergic activity at the SCN is necessary for arousal-induced phase shifting. Finally, we demonstrate that electrical stimulation of the substantia innominata of the basal forebrain phase shifts the circadian clock in a manner similar to that of our arousal procedures and that these shifts are also blocked by infusions of atropine to the SCN. These results establish a functional link between the major forebrain arousal center and the circadian system. PMID:27821764

Automated activity-aware prompting for activity initiation.

PubMed

Holder, Lawrence B; Cook, Diane J

2013-01-01

Performing daily activities without assistance is important to maintaining an independent functional lifestyle. As a result, automated activity prompting systems can potentially extend the period of time that adults can age in place. In this paper we introduce AP, an algorithm to automate activity prompting based on smart home technology. AP learns prompt rules based on the time when activities are typically performed as well as the relationship between activities that normally occur in a sequence. We evaluate the AP algorithm based on smart home datasets and demonstrate its ability to operate within a physical smart environment.

Sextant X-Ray Pulsar Navigation Demonstration: Initial On-Orbit Results

NASA Technical Reports Server (NTRS)

Mitchell, Jason W.; Winternitz, Luke M.; Hassouneh, Munther A.; Price, Samuel R.; Semper, Sean R.; Yu, Wayne H.; Ray, Paul S.; Wolff, Michael T.; Kerr, Matthew; Wood, Kent S.;

The effect of Platelet Lysate on osteoblast proliferation associated with a transient increase of the inflammatory response in bone regeneration.

PubMed

Ruggiu, Alessandra; Ulivi, Valentina; Sanguineti, Francesca; Cancedda, Ranieri; Descalzi, Fiorella

2013-12-01

Platelet Lysate (PL) contains a cocktail of growth factors and cytokines, which actively participates in tissue repair and its clinical application has been broadly described. The aim of this study was to assess the regenerative potential of PL for bone repair. We demonstrated that PL stimulation induces a transient increase of the inflammatory response in quiescent human osteoblasts, via NF-kB activation, COX-2 induction, PGE2 production and secretion of pro-inflammatory cytokines. Furthermore, we showed that long-term PL stimulation enhances proliferation of actively replicating osteoblasts, without affecting their differentiation potential, along with changes of cell morphology, resulting in increased cell density at confluence. In confluent resting osteoblasts, PL treatment induced resumption of proliferation, change in cell morphology and increase of cell density at confluence. A burst of PL treatment (24-h) was sufficient to trigger such processes in both conditions. These results correlated with up-regulation of the proliferative and survival pathways ERKs and Akt and with cell cycle re-activation via induction of CyclinD1 and phosphorylation of Rb, following PL stimulation. Our findings demonstrate that PL treatment results in activation and expansion of resting osteoblasts, without affecting their differentiation potential. Therefore PL represents a good therapeutic candidate in regenerative medicine for bone repair. Copyright © 2013 Elsevier Ltd. All rights reserved.

TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway.

PubMed

Pombo, Mónica; Lamé, Michael W; Walker, Naomi J; Huynh, Danh H; Tablin, Fern

2015-05-19

The role of the aryl hydrocarbon receptor (AhR) in hemostasis has recently gained increased attention. Here, we demonstrate, by qRT-PCR and western blot, that human platelets express both AhR mRNA and AhR protein. AhR protein levels increase in a dose dependent manner when incubated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole. Treatment of platelets with puromycin blocks increased AhR protein synthesis in the presence of AhR activators. Additionally, treatment of platelets with either activator results in phosphorylation of p38MAPK and cPLA2, two key signaling molecules in platelet activation pathways. Using the AhR competitive inhibitors alpha naphthoflavone and CH-223191, we show that phosphorylation of p38MAPK is AhR dependent. Further, inhibition of p38MAPK blocks downstream cPLA2 phosphorylation induced by TCDD or omeprazole. Treatment with AhR activators results in platelet priming, as demonstrated by increased platelet aggregation, which is inhibited by AhR antagonists. Our data support a model of the platelet AhR non-genomic pathway in which treatment with AhR activators results in increased expression of the AhR, phosphorylation of p38MAPK and cPLA2, leading to platelet priming in response to agonist. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

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

Arulanandam, Rozanne; Geletu, Mulu; Feracci, Helene

2010-03-10

Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac{sup V12}), at different cell densities. The results revealedmore » for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac{sup V12} with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac{sup V12}-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac{sup V12} is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac{sup V12} expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac{sup V12}. The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac{sup V12}, as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.« less

Multi-mode Intravascular RF Coil for MRI-guided Interventions

PubMed Central

Kurpad, Krishna N.; Unal, Orhan

2011-01-01

Purpose To demonstrate the feasibility of using a single intravascular RF probe connected to the external MRI system via a single coaxial cable to perform active tip tracking and catheter visualization, and high SNR intravascular imaging. Materials and Methods A multi-mode intravascular RF coil was constructed on a 6F balloon catheter and interfaced to a 1.5T MRI scanner via a decoupling circuit. Bench measurements of coil impedances were followed by imaging experiments in saline and phantoms. Results The multi-mode coil behaves as an inductively-coupled transmit coil. Forward looking capability of 6mm is measured. Greater than 3-fold increase in SNR compared to conventional imaging using optimized external coil is demonstrated. Simultaneous active tip tracking and catheter visualization is demonstrated. Conclusions It is feasible to perform 1) active tip tracking, 2) catheter visualization, and 3) high SNR imaging using a single multi-mode intravascular RF coil that is connected to the external system via a single coaxial cable. PMID:21448969

Selective Hydrodeoxygenation of 5-Hydroxymethylfurfural to 2,5-Dimethylfuran over Heterogeneous Iron Catalysts.

PubMed

Li, Jiang; Liu, Jun-Ling; Liu, He-Yang; Xu, Guang-Yue; Zhang, Jun-Jie; Liu, Jia-Xing; Zhou, Guang-Lin; Li, Qin; Xu, Zhi-Hao; Fu, Yao

2017-04-10

This work provided the first example of selective hydrodeoxygenation of 5-hydroxymethylfurfural (HMF) to 2,5-dimethylfuran (DMF) over heterogeneous Fe catalysts. A catalyst prepared by the pyrolysis of an Fe-phenanthroline complex on activated carbon at 800 °C was demonstrated to be the most active heterogeneous Fe catalyst. Under the optimal reaction conditions, complete conversion of HMF was achieved with 86.2 % selectivity to DMF. The reaction pathway was investigated thoroughly, and the hydrogenation of the C=O bond in HMF was demonstrated to be the rate-determining step during the hydrodeoxygenation, which could be accelerated greatly by using alcohol solvents as additional H-donors. The excellent stability of the Fe catalyst, which was probably a result of the well-preserved active species and the pore structure of the Fe catalyst in the presence of H 2 , was demonstrated in batch and continuous flow fixed-bed reactors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of metabolically stable 5′-phosphate analogs that support single-stranded siRNA activity

PubMed Central

Prakash, Thazha P.; Lima, Walt F.; Murray, Heather M.; Li, Wenyu; Kinberger, Garth A.; Chappell, Alfred E.; Gaus, Hans; Seth, Punit P.; Bhat, Balkrishen; Crooke, Stanley T.; Swayze, Eric E.

2015-01-01

The ss-siRNA activity in vivo requires a metabolically stable 5′-phosphate analog. In this report we used crystal structure of the 5′-phosphate binding pocket of Ago-2 bound with guide strand to design and synthesize ss-siRNAs containing various 5′-phosphate analogs. Our results indicate that the electronic and spatial orientation of the 5′-phosphate analog was critical for ss-siRNA activity. Chemically modified ss-siRNA targeting human apoC III mRNA demonstrated good potency for inhibiting ApoC III mRNA and protein in transgenic mice. Moreover, ApoC III ss-siRNAs were able to reduce the triglyceride and LDL cholesterol in transgenic mice demonstrating pharmacological effect of ss-siRNA. Our study provides guidance to develop surrogate phosphate analog for ss-siRNA and demonstrates that ss-siRNA provides an alternative strategy for therapeutic gene silencing. PMID:25753666

Application of neural networks with orthogonal activation functions in control of dynamical systems

NASA Astrophysics Data System (ADS)

Nikolić, Saša S.; Antić, Dragan S.; Milojković, Marko T.; Milovanović, Miroslav B.; Perić, Staniša Lj.; Mitić, Darko B.

2016-04-01

In this article, we present a new method for the synthesis of almost and quasi-orthogonal polynomials of arbitrary order. Filters designed on the bases of these functions are generators of generalised quasi-orthogonal signals for which we derived and presented necessary mathematical background. Based on theoretical results, we designed and practically implemented generalised first-order (k = 1) quasi-orthogonal filter and proved its quasi-orthogonality via performed experiments. Designed filters can be applied in many scientific areas. In this article, generated functions were successfully implemented in Nonlinear Auto Regressive eXogenous (NARX) neural network as activation functions. One practical application of the designed orthogonal neural network is demonstrated through the example of control of the complex technical non-linear system - laboratory magnetic levitation system. Obtained results were compared with neural networks with standard activation functions and orthogonal functions of trigonometric shape. The proposed network demonstrated superiority over existing solutions in the sense of system performances.

Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells.

PubMed

Deus, Cláudia M; Serafim, Teresa L; Magalhães-Novais, Silvia; Vilaça, Andreia; Moreira, Ana C; Sardão, Vilma A; Cardoso, Susana M; Oliveira, Paulo J

2017-03-01

Sirtuins regulate several processes associated with tumor development. Resveratrol was shown to stimulate sirtuin 1 and 3 (SIRT1/3) activities and to result in cytotoxicity for some tumor types. The relationship between modulation of sirtuin activities, cellular metabolic remodeling and resveratrol cytotoxicity mechanism on breast cancer cells is still an open question. Here, we evaluated whether sirtuin 1 and 3 are involved in resveratrol toxicity and whether resveratrol leads to a metabolic remodeling and cell differentiation. Results using the Extracellular Flux Analyzer indicated that resveratrol inhibits mitochondrial respiration in breast cancer cells. We also demonstrated here for the first time that resveratrol cytotoxic effects on breast cancer cells were modulated by SIRT1 and also involved mitochondrial complex I inhibition. Importantly, we also demonstrated that resveratrol reduced the pool of breast cancer cells with stemness markers through a SIRT1-dependent mechanism. Our data highlights the role of SIRT1 in regulating resveratrol induced differentiation and/or toxicity in breast cancer cells.

Cyclooxygenase-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 in breast cancer cells.

PubMed

Chuang, Chun-Wei; Pan, Mei-Ren; Hou, Ming-Feng; Hung, Wen-Chun

2013-02-01

Up-regulation of cyclooxygenase-2 (COX-2) is frequently found in human cancers and is significantly associated with tumor metastasis. Our previous results demonstrate that COX-2 and its metabolite prostaglandin E2 (PGE2) stimulate the expression of CCR7 chemokine receptor via EP2/EP4 receptors to promote lymphatic invasion in breast cancer cells. In this study, we address the underlying mechanism of COX-2/PGE2-induced CCR7 expression. We find that COX-2/PGE2 increase CCR7 expression via the AKT signaling pathway in breast cancer cells. Promoter deletion and mutation assays identify the Sp1 site located at the -60/-57 region of CCR7 gene promoter is critical for stimulation. Chromatin immunoprecipitation (ChIP) assay confirms that in vivo binding of Sp1 to human CCR7 promoter is increased by COX-2 and PGE2. Knockdown of Sp1 by shRNA reduces the induction of CCR7 by PGE2. We demonstrate for the first time that AKT may directly phosphorylate Sp1 at S42, T679, and S698. Phosphorylation-mimic Sp1 protein harboring S42D, T679D, and S698D mutation strongly activates CCR7 expression. In contrast, change of these three residues to alanine completely blocks the induction of CCR7 by PGE2. Pathological investigation demonstrates that CCR7 expression is strongly associated with phospho-AKT and Sp1 in 120 breast cancer tissues. Collectively, our results demonstrate that COX-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 and this pathway is highly activated in metastatic breast cancer. Copyright © 2012 Wiley Periodicals, Inc.

Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity.

PubMed

Corcóstegui, Reyes; Labeaga, Luis; Innerárity, Ana; Berisa, Agustin; Orjales, Aurelio

2005-01-01

This study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist. In vitro experiments were conducted using a receptor binding screening panel and guinea-pig and rat tissues. Antihistaminic activity was determined using H1 receptor binding studies and in vitro H1 antagonism studies conducted in guinea-pig tissues and human cell lines. Receptor selectivity was established using a receptor binding screening panel and a receptor antagonism screening conducted in guinea-pig, rat and rabbit tissues. Inhibition of inflammatory mediators was determined through the Schultz-Dale reaction in sensitised guinea-pig ileum. Bilastine binds to histamine H1-receptors as indicated by its displacement of [3H]-pyrilamine from H1-receptors expressed in guinea-pig cerebellum and human embryonic kidney (HEK) cell lines. The studies conducted on guinea-pig smooth muscle demonstrated the capability of bilastine to antagonise H1-receptors. Bilastine is selective for histamine H1-receptors as shown in receptor-binding screening conducted to determine the binding capacity of bilastine to 30 different receptors. The specificity of its H1-receptor antagonistic activity was also demonstrated in a series of in vitro experiments conducted on guinea-pig and rat tissues. The results of these studies confirmed the lack of significant antagonism against serotonin, bradykinin, leukotriene D4, calcium, muscarinic M3-receptors, alpha1-adrenoceptors, beta2-adrenoceptors, and H2- and H3-receptors. The results of the in vitro Schultz-Dale reaction demonstrated that bilastine also has anti-inflammatory activity. These preclinical studies provide evidence that bilastine has H1- antihistamine activity, with high specificity for H1-receptors, and poor or no affinity for other receptors. Bilastine has also been shown to have anti-inflammatory properties.

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

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

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlyingmore » the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR and phosphorylation of ERK.« less

A Cellular Mechanism for Dendritic Spine Loss in the Pilocarpine Model of Status Epilepticus

PubMed Central

Kurz, Jonathan E.; Moore, Bryan J.; Henderson, Scott; Campbell, John N.; Churn, Severn B.

2013-01-01

Purpose Previous studies have documented a synaptic translocation of calcineurin (CaN) and increased CaN activity following status epilepticus (SE), however the cellular effect of these changes in CaN in the pathology of SE remains to be elucidated. This study examined a CaN-dependent modification of the dendritic cytoskeleton. CaN has been shown to induce dephosphorylation of cofilin, an actin depolymerization factor. The ensuing actin depolymerization can lead to a number of physiological changes that are of interest in SE. Methods SE was induced by pilocarpine injection, and seizure activity was monitored by video-EEG. Subcellular fractions were isolated by differential centrifugation. CaN activity was assayed using a para-nitrophenol phosphate assay protocol. Cofilin phosphorylation was assessed using phosphocofilin-specific antibodies. Cofilin-actin binding was determined by co-immunoprecipitation, and actin polymerization was measured using a triton-solubilization protocol. Spines were visualized using a single-section rapid Golgi impregnation procedure. Results The immunoreactivity of phosphocofilin decreased significantly in hippocampal and cortical synaptosomal samples after SE. SE-induced cofilin dephosphorylation could be partially blocked by the pre-injection of CaN inhibitors. Cofilin activation could be further demonstrated by increased actin-cofilin binding and a significant depolymerization of neuronal actin, both of which were also blocked by CaN inhibitors. Finally, we demonstrated a CaN-dependent loss of dendritic spines histologically. Discussion The data demonstrate a CaN-dependent, cellular mechanism through which prolonged seizure activity results in loss of dendritic spines via cofilin activation. Further research into this area may provide useful insights into the pathology of SE and epileptogenic mechanisms. PMID:18479390

A study for active control research and validation using the Total In-Flight Simulator (TIFS) aircraft

NASA Technical Reports Server (NTRS)

Chen, R. T. N.; Daughaday, H.; Andrisani, D., II; Till, R. D.; Weingarten, N. C.

1975-01-01

The results of a feasibility study and preliminary design for active control research and validation using the Total In-Flight Simulator (TIFS) aircraft are documented. Active control functions which can be demonstrated on the TIFS aircraft and the cost of preparing, equipping, and operating the TIFS aircraft for active control technology development are determined. It is shown that the TIFS aircraft is as a suitable test bed for inflight research and validation of many ACT concepts.

Disordered anodes for Ni-metal rechargeable battery

DOEpatents

Young, Kwo-hsiung; Wang, Lixin; Mays, William C.

2016-11-22

An electrochemical cell is provided that includes a structurally and compositionally disordered electrochemically active alloy material as an anode active material with unexpected capacity against a nickel hydroxide based cathode active material. The disordered metal hydroxide alloy includes three or more transition metal elements and is formed in such a way so as to produce the necessary disorder in the overall system. When an anode active material includes nickel as a predominant, the resulting cells represent the first demonstration of a functional Ni/Ni cell.

Evaluation of muscle activity for loaded and unloaded dynamic squats during vertical whole-body vibration.

PubMed

Hazell, Tom J; Kenno, Kenji A; Jakobi, Jennifer M

2010-07-01

The purpose of this investigation was to examine if the addition of a light external load would enhance whole-body vibration (WBV)-induced increases in muscle activity during dynamic squatting in 4 leg muscles. Thirteen recreationally active male university students performed a series of dynamic squats (unloaded with no WBV, unloaded with WBV, loaded with no WBV, and loaded with WBV). The load was set to 30% of body mass and WBV included 25-, 35-, and 45-Hz frequencies with 4-mm amplitude. Muscle activity was recorded with surface electromyography (EMG) on the vastus lateralis (VL), biceps femoris (BF), tibialis anterior (TA), and gastrocnemius (GC) and is reported as EMGrms (root mean square) normalized to %maximal voluntary exertion. During unloaded dynamic squats, exposure to WBV (45 Hz) significantly (p < 0.05) increased baseline muscle activity in all muscles, except the TA compared with no WBV. Adding a light external load without WBV increased baseline muscle activity of the squat exercise in all muscles but decreased the TA. This loaded level of muscle activity was further increased with WBV (45 Hz) in all muscles. The WBV-induced increases in muscle activity in the loaded condition (approximately 3.5%) were of a similar magnitude to the WBV-induced increases during the unloaded condition (approximately 2.5%) demonstrating the addition of WBV to unloaded or loaded dynamic squatting results in an increase in muscle activity. These results demonstrate the potential effectiveness of using external loads with exposure to WBV.

Understanding Recombination.

ERIC Educational Resources Information Center

Zimmerman, Ira

2003-01-01

Describes a science activity on the importance of meiosis for variability. Uses a coin flip to demonstrate the random arrangement of genetic materials and explains how this results in zygotes with a new DNA combination. (YDS)

Effects of Selective Checkpoint Kinase 1 Inhibition on Cytarabine Cytotoxicity in Acute Myelogenous Leukemia Cells in Vitro

PubMed Central

Schenk, Erin L.; Koh, Brian D.; Flatten, Karen S.; Peterson, Kevin L.; Parry, David; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Karnitz, Larry M.; Kaufmann, Scott H.

2012-01-01

Purpose Previous studies have demonstrated that the replication checkpoint, which involves the kinases ATR and Chk1, contributes to cytarabine resistance in cell lines. In the present study, we examined whether this checkpoint is activated in clinical AML during cytarabine infusion in vivo and then assessed the impact of combining cytarabine with the recently described Chk1 inhibitor SCH 900776 in vitro. Experimental design AML marrow aspirates harvested before and during cytarabine infusion were examined by immunoblotting. Human AML lines treated with cytarabine in the absence or presence of SCH 900776 were assayed for checkpoint activation by immunoblotting, nucleotide incorporation into DNA and flow cytometry. Long-term effects in AML lines, clinical AML isolates, and normal myeloid progenitors were assayed using clonogenic assays. Results Immunoblotting demonstrated increased Chk1 phosphorylation, a marker of checkpoint activation, in over half of Chk1-containing AMLs after 48 h of cytarabine infusion. In human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation and S phase arrest, but also markedly increased cytarabine-induced apoptosis. Clonogenic assays demonstrated that SCH 900776 enhanced the anti-proliferative effects of cytarabine in AML cell lines and clinical AML samples at concentrations that had negligible impact on normal myeloid progenitors. Conclusions These results not only provide evidence for cytarabine-induced S phase checkpoint activation in AML in the clinical setting, but also show that a selective Chk1 inhibitor can overcome the S phase checkpoint and enhance the cytotoxicity of cytarabine. Accordingly, further investigation of the cytarabine/SCH 900776 combination in AML appears warranted. PMID:22869869

Exploring the transcription activator-like effectors scaffold versatility to expand the toolbox of designer nucleases

PubMed Central

2014-01-01

Background The past decade has seen the emergence of several molecular tools that render possible modification of cellular functions through accurate and easy addition, removal, or exchange of genomic DNA sequences. Among these technologies, transcription activator-like effectors (TALE) has turned out to be one of the most versatile and incredibly robust platform for generating targeted molecular tools as demonstrated by fusion to various domains such as transcription activator, repressor and nucleases. Results In this study, we generated a novel nuclease architecture based on the transcription activator-like effector scaffold. In contrast to the existing Tail to Tail (TtT) and head to Head (HtH) nuclease architectures based on the symmetrical association of two TALE DNA binding domains fused to the C-terminal (TtT) or N-terminal (HtH) end of FokI, this novel architecture consists of the asymmetrical association of two different engineered TALE DNA binding domains fused to the N- and C-terminal ends of FokI (TALE::FokI and FokI::TALE scaffolds respectively). The characterization of this novel Tail to Head (TtH) architecture in yeast enabled us to demonstrate its nuclease activity and define its optimal target configuration. We further showed that this architecture was able to promote substantial level of targeted mutagenesis at three endogenous loci present in two different mammalian cell lines. Conclusion Our results demonstrated that this novel functional TtH architecture which requires binding to only one DNA strand of a given endogenous locus has the potential to extend the targeting possibility of FokI-based TALE nucleases. PMID:24997498

A synthetic cannabinoid JWH-210 reduces lymphoid organ weights and T-cell activator levels in mice via CB2 receptors.

PubMed

Gu, Sun Mi; Lee, Hyun Jin; Lee, Tac-Hyung; Song, Yun Jeong; Kim, Young-Hoon; Han, Kyoung-Moon; Shin, Jisoon; Park, Hye-Kyung; Kim, Hyung Soo; Cha, Hye Jin; Yun, Jaesuk

2017-12-01

The problem of new psychoactive substances (NPS) is emerging globally. However, the immunotoxicity of synthetic cannabinoids is not evaluated extensively yet. The purpose of the present study was to investigate whether synthetic cannabinoids (JWH-210 and JWH-030) induce adverse effects on lymphoid organs, viability of splenocytes and thymocytes, and immune cell activator and cytokines in mice. JWH-210 (10 mg/kg, 3 days, i.p.) is more likely to have cytotoxicity and reduce lymphoid organ weight than JWH-030 of ICR mice in vivo. We also demonstrated that JWH-210 administration resulted in the decrease of expression levels of T-cell activator including Cd3e, Cd3g, Cd74p31, and Cd74p41, while JWH-030 increased Cd3g levels. In addition, JWH-210 reduced expression levels of cytokines, such as interleukin-3, interleukin-5, and interleukin-6. Furthermore, we demonstrated that a CB 2 receptor antagonist, AM630 inhibited JWH-210-induced cytotoxicity, whereas a CB 1 receptor antagonist, rimonabant did not in primary cultured splenocytes. These results suggest that JWH-210 has a cytotoxicity via CB 2 receptor action and results in decrement of lymphoid organ weights, T-cell activator, and cytokine mRNA expression levels.

Synthesis, characterization, and anticancer activity of new quinazoline derivatives against MCF-7 cells.

PubMed

Faraj, Fadhil Lafta; Zahedifard, Maryam; Paydar, Mohammadjavad; Looi, Chung Yeng; Abdul Majid, Nazia; Ali, Hapipah Mohd; Ahmad, Noraini; Gwaram, Nura Suleiman; Abdulla, Mahmood Ameen

2014-01-01

Two new synthesized and characterized quinazoline Schiff bases 1 and 2 were investigated for anticancer activity against MCF-7 human breast cancer cell line. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an IC50 value of 6.246×10(-6) mol/L and 5.910×10(-6) mol/L, respectively, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with 1 and 2 subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS formation. We also found activation of caspases-3/7, -8, and -9 in compounds 1 and 2. Moreover, inhibition of NF-κB translocation in MCF-7 cells treated by compound 1 significantly exhibited the association of extrinsic apoptosis pathway. Acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed significant activity towards MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway and are potential candidate for further in vivo and clinical breast cancer studies.

Synthesis, Characterization, and Anticancer Activity of New Quinazoline Derivatives against MCF-7 Cells

PubMed Central

Faraj, Fadhil Lafta; Zahedifard, Maryam; Paydar, Mohammadjavad; Looi, Chung Yeng; Abdul Majid, Nazia; Ali, Hapipah Mohd; Ahmad, Noraini; Gwaram, Nura Suleiman; Abdulla, Mahmood Ameen

2014-01-01

Two new synthesized and characterized quinazoline Schiff bases 1 and 2 were investigated for anticancer activity against MCF-7 human breast cancer cell line. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an IC50 value of 6.246 × 10−6 mol/L and 5.910 × 10−6 mol/L, respectively, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with 1 and 2 subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS formation. We also found activation of caspases-3/7, -8, and -9 in compounds 1 and 2. Moreover, inhibition of NF-κB translocation in MCF-7 cells treated by compound 1 significantly exhibited the association of extrinsic apoptosis pathway. Acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed significant activity towards MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway and are potential candidate for further in vivo and clinical breast cancer studies. PMID:25548779

Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis.

PubMed

Lin, Wensheng; Lin, Yifeng; Li, Jin; Fenstermaker, Ali G; Way, Sharon W; Clayton, Benjamin; Jamison, Stephanie; Harding, Heather P; Ron, David; Popko, Brian

2013-04-03

There is compelling evidence that oligodendrocyte apoptosis, in response to CNS inflammation, contributes significantly to the development of the demyelinating disorder multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Therefore, approaches designed to protect oligodendrocytes would likely have therapeutic value. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum (ER) stress increases cell survival under various cytotoxic conditions. Moreover, there is evidence that PERK signaling is activated in oligodendrocytes within demyelinating lesions in multiple sclerosis and EAE. Our previous study demonstrated that CNS delivery of the inflammatory cytokine interferon-γ before EAE onset protected mice against EAE, and this protection was dependent on PERK signaling. In our current study, we sought to elucidate the role of PERK signaling in oligodendrocytes during EAE. We generated transgenic mice that allow for temporally controlled activation of PERK signaling, in the absence of ER stress, specifically in oligodendrocytes. We demonstrated that persistent activation of PERK signaling was not deleterious to oligodendrocyte viability or the myelin of adult animals. Importantly, we found that enhanced activation of PERK signaling specifically in oligodendrocytes significantly attenuated EAE disease severity, which was associated with reduced oligodendrocyte apoptosis, demyelination, and axonal degeneration. This effect was not the result of an altered degree of the inflammatory response in EAE mice. Our results provide direct evidence that activation of PERK signaling in oligodendrocytes is cytoprotective, protecting mice against EAE.

Platelet Kainate Receptor Signaling Promotes Thrombosis by Stimulating Cyclooxygenase Activation

PubMed Central

Sun, Henry; Swaim, AnneMarie; Herrera, Jesus Enrique; Becker, Diane; Becker, Lewis; Srivastava, Kalyan; Thompson, Laura E.; Shero, Michelle R.; Perez-Tamayo, Alita; Suktitpat, Bhoom; Mathias, Rasika; Contractor, Anis; Faraday, Nauder; Morrell, Craig N.

2009-01-01

Rationale Glutamate is a major signaling molecule that binds to glutamate receptors including the ionotropic glutamate receptors; kainate (KA) receptor (KAR), the N-methyl-D-aspartate (NMDA) receptor (NMDAR), and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR). Each is well characterized in the central nervous system (CNS), but glutamate has important signaling roles in peripheral tissues as well, including a role in regulating platelet function. Objective Our previous work has demonstrated that glutamate is released by platelets in high concentrations within a developing thrombus and increases platelet activation and thrombosis. We now show that platelets express a functional KAR that drives increased agonist induced platelet activation. Methods and Results KAR induced increase in platelet activation is in part the result of activation of platelet cyclooxygenase (COX) in a Mitogen Activated Protein Kinase (MAPK) dependent manner. Platelets derived from KA receptor subunit knockout mice (GluR6−/−) are resistant to KA effects and have a prolonged time to thrombosis in vivo. Importantly, we have also identified polymorphisms in KA receptor subunits that are associated with phenotypic changes in platelet function in a large group of Caucasians and African Americans. Conclusion Our data demonstrate that glutamate regulation of platelet activation is in part COX dependent, and suggest that the KA receptor is a novel anti-thrombotic target. PMID:19679838

Study of the antibacterial activity of electro-activated solutions of salts of weak organic acids on Salmonella enterica, Staphylococcus aureus and Listeria monocytogenes.

PubMed

Liato, Viacheslav; Labrie, Steve; Aïder, Mohammed

2017-01-01

This work assessed the antibacterial activity of electro-activated solutions of salts of weak organic acids (potassium acetate, potassium citrate and calcium lactate) on Salmonella enterica, Staphylococcus aureus and Listeria monocytogenes. This activity was compared in terms of minimal inhibitory (bactericidal) concentration to the effect of commercial acetic, citric and lactic acid at equivalent titratable acidity. Staining live/dead BacLight method was used to consider physiological state of bacteria following the evaluation of pathogenic strains during exposure to the tested solutions. The results demonstrated strong inhibitory activity of all electro-activated solutions. After 10 min of exposure to electro-activated potassium acetate, a reduction of ≥6 log CFU/ml of all bacteria was observed. The electro-activated potassium citrate demonstrated the lowest minimal inhibitory concentration. Nevertheless, its inactivation power was significantly higher than that of conjugated citric acid. Although electro-activated calcium lactate was found less effective in comparison with its conjugated acid form, after 10 min of contact with the tested pathogens, it induced a population reduction of 2.23, 2.97 and 5.57 log CFU/ml of S. aureus, L. monocytogenes and S. enterica, respectively.

Removing the barrier to the calculation of activation energies: Diffusion coefficients and reorientation times in liquid water.

PubMed

Piskulich, Zeke A; Mesele, Oluwaseun O; Thompson, Ward H

2017-10-07

General approaches for directly calculating the temperature dependence of dynamical quantities from simulations at a single temperature are presented. The method is demonstrated for self-diffusion and OH reorientation in liquid water. For quantities which possess an activation energy, e.g., the diffusion coefficient and the reorientation time, the results from the direct calculation are in excellent agreement with those obtained from an Arrhenius plot. However, additional information is obtained, including the decomposition of the contributions to the activation energy. These results are discussed along with prospects for additional applications of the direct approach.

Creatine Kinase Activity Weakly Correlates to Volume Completed Following Upper Body Resistance Exercise

ERIC Educational Resources Information Center

Machado, Marco; Willardson, Jeffrey M.; Silva, Dailson P.; Frigulha, Italo C.; Koch, Alexander J.; Souza, Sergio C.

2012-01-01

In the current study, we examined the relationship between serum creatine kinase (CK) activity following upper body resistance exercise with a 1- or 3-min rest between sets. Twenty men performed two sessions, each consisting of four sets with a 10-repetition maximum load. The results demonstrated significantly greater volume for the 3-min…

Microbial survey of a full-scale, biologically active filter for treatment of drinking water.

PubMed

White, Colin P; Debry, Ronald W; Lytle, Darren A

2012-09-01

The microbial community of a full-scale, biologically active drinking water filter was surveyed using molecular techniques. Nitrosomonas, Nitrospira, Sphingomonadales, and Rhizobiales dominated the clone libraries. The results elucidate the microbial ecology of biological filters and demonstrate that biological treatment of drinking water should be considered a viable alternative to physicochemical methods.

Function Follows Form: Activation of Shape and Function Features during Object Identification

ERIC Educational Resources Information Center

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

2011-01-01

Most theories of semantic memory characterize knowledge of a given object as comprising a set of semantic features. But how does conceptual activation of these features proceed during object identification? We present the results of a pair of experiments that demonstrate that object recognition is a dynamically unfolding process in which function…

A Planning Tool for Incorporating Backward Design, Active Learning, and Authentic Assessment in the College Classroom

ERIC Educational Resources Information Center

Reynolds, Heather L.; Kearns, Katherine Dowell

2017-01-01

Backward course design is a compelling strategy for achieving results-based, student-centered learning. The backward course-design approach is first to identify student-learning outcomes, then the means of assessing the outcomes, and lastly the classroom activities that would support the learning outcomes. With demonstrated success at improving…

Functional regeneration of the ex-vivo reconstructed mesocorticolimbic dopaminergic system.

PubMed

Dossi, Elena; Heine, Claudia; Servettini, Ilenio; Gullo, Francesca; Sygnecka, Katja; Franke, Heike; Illes, Peter; Wanke, Enzo

2013-12-01

CNS reparative-medicine therapeutic strategies need answers on the putative recapitulation of the basic rules leading to mammalian CNS development. To achieve this aim, we focus on the regeneration of functional connections in the mesocorticolimbic dopaminergic system. We used organotypic slice cocultures of ventral tegmental area/substantia nigra (VTA/SN) and prefrontal cortex (PFC) on a multielectrode array (MEA) platform to record spikes and local field potentials. The spontaneously growing synaptically based bidirectional bursting activity was followed from 2 to 28 days in vitro (DIV). A statistical analysis of excitatory and inhibitory neurons properties of the physiological firing activity demonstrated a remarkable, exponentially increasing maturation with a time constant of about 5-7 DIV. Immunohistochemistry demonstrated that the ratio of excitatory/inhibitory neurons (3:1) was in line with the functional results obtained. Exemplary pharmacology suggested that GABAA receptors were able to exert phasic and tonic inhibition typical of an adulthood network. Moreover, dopamine D2 receptor inactivation was equally inhibitory both on the spontaneous neuronal activity recorded by MEA and on patch-clamp electrophysiology in PFC pyramidal neurons. These results demonstrate that axon growth cones reach synaptic targets up to full functionality and that organotypic cocultures of the VTA/SN-PFC perfectly model their newly born dopaminergic, glutamatergic and GABAergic neuronal circuitries.

Berberine enhances the anti‑tumor activity of tamoxifen in drug‑sensitive MCF‑7 and drug‑resistant MCF‑7/TAM cells.

PubMed

Wen, Chunjie; Wu, Lanxiang; Fu, Lijuan; Zhang, Xue; Zhou, Honghao

2016-09-01

Berberine, an isoquinoline alkaloid, has been previously demonstrated to possess anti‑breast cancer properties. Tamoxifen is widely used in the prevention and treatment of estrogen receptor-positive breast cancer. Thus, the aim of the present study was to assess whether berberine enhanced the anticancer effect of tamoxifen, and the underlying mechanism involved in this combined effect in tamoxifen-sensitive (MCF-7) and tamoxifen-resistant (MCF-7/TAM) cells using MTS, flow cytometry and western blot assays. The results indicated that berberine demonstrated dose‑ and time‑dependent anti‑proliferative activity in MCF‑7 and MCF‑7/TAM cells. Furthermore, the combination of berberine and tamoxifen induced cell growth inhibition more effectively than tamoxifen alone. The present study also demonstrated that combinational treatment is more effective in inducing G1 phase arrest and activating apoptosis compared tamoxifen alone, which may be due to upregulation of P21 expression and downregulation of the B‑cell CLL/lymphoma 2(Bcl‑2)/Bcl‑2 associated X protein ratio. The results of the present study suggested that berberine may potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen, which will be useful for anti‑tumor therapy and further research.

Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery

PubMed Central

Martinez, Jonathan O.; Molinaro, Roberto; Hartman, Kelly A.; Boada, Christian; Sukhovershin, Roman; De Rosa, Enrica; Kirui, Dickson; Zhang, Shanrong; Evangelopoulos, Michael; Carter, Angela M.; Bibb, James A.; Cooke, John P.; Tasciotti, Ennio

2018-01-01

Activation of the vascular endothelium is characterized by increased expression of vascular adhesion molecules and chemokines. This activation occurs early in the progression of several diseases and triggers the recruitment of leukocytes. Inspired by the tropism of leukocytes, we investigated leukocyte-based biomimetic nanoparticles (i.e., leukosomes) as a novel theranostic platform for inflammatory diseases. Methods: Leukosomes were assembled by combining phospholipids and membrane proteins from leukocytes. For imaging applications, phospholipids modified with rhodamine and gadolinium were used. Leukosomes incubated with antibodies blocking lymphocyte function-associated antigen 1 (LFA-1) and CD45 were administered to explore their roles in targeting inflammation. In addition, relaxometric assessment of NPs was evaluated. Results: Liposomes and leukosomes were both spherical in shape with sizes ranging from 140-170 nm. Both NPs successfully integrated 8 and 13 µg of rhodamine and gadolinium, respectively, and demonstrated less than 4% variation in physicochemical features. Leukosomes demonstrated a 16-fold increase in breast tumor accumulation relative to liposomes. Furthermore, quantification of leukosomes in tumor vessels demonstrated a 4.5-fold increase in vessel lumens and a 14-fold increase in vessel walls. Investigating the targeting mechanism of action revealed that blockage of LFA-1 on leukosomes resulted in a 95% decrease in tumor accumulation. Whereas blockage of CD45 yielded a 60% decrease in targeting and significant increases in liver and spleen accumulation. In addition, when administered in mice with atherosclerotic plaques, leukosomes exhibited a 4-fold increase in the targeting of inflammatory vascular lesions. Lastly, relaxometric assessment of NPs demonstrated that the incorporation of membrane proteins into leukosomes did not impact the r1 and r2 relaxivities of the NPs, demonstrating 6 and 30 mM-1s-1, respectively. Conclusion: Our study demonstrates the ability of leukosomes to target activated vasculature and exhibit superior accumulation in tumors and vascular lesions. The versatility of the phospholipid backbone within leukosomes permits the incorporation of various contrast agents. Furthermore, leukosomes can potentially be loaded with therapeutics possessing diverse physical properties and thus warrant further investigation toward the development of powerful theranostic agents. PMID:29464004

Protein oxidation and degradation during proliferative senescence of human MRC-5 fibroblasts.

PubMed

Sitte, N; Merker, K; von Zglinicki, T; Grune, T

2000-03-01

One of the highlights of age-related changes of cellular metabolism is the accumulation of oxidized proteins. The aging process on a cellular level can be treated either as the ongoing proliferation until a certain number of cell divisions is reached (the Hayflick limit) or as the aging of nondividing cells, that is, the age-related changes in cells without proliferation. The present investigation was undertaken to reveal the changes in protein turnover, proteasome activity, and protein oxidation status during proliferative senescence. We were able to demonstrate that the activity of the cytosolic proteasomal system declines dramatically during the proliferative senescence of human MRC-5 fibroblasts. Regardless of the loss in activity, it could be demonstrated that there are no changes in the transcription and translation of proteasomal subunits. This decline in proteasome activity was accompanied by an increased concentration of oxidized proteins. Cells at higher proliferation stages were no longer able to respond with increased degradation of endogenous [(35)S]-Met-radiolabeled proteins after hydrogen peroxide- or quinone-induced oxidative stress. It could be demonstrated that oxidized proteins in senescent human MRC-5 fibroblasts are not as quickly removed as they are in young cells. Therefore, our study demonstrates that the accumulation of oxidized proteins and decline in protein turnover and activity of the proteasomal system are not only a process of postmitotic aging but also occur during proliferative senescence and result in an increased half-life of oxidized proteins.

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma

PubMed Central

Torok, Kathryn S.; Kurzinski, Katherine; Kelsey, Christina; Yabes, Jonathan; Magee, Kelsey; Vallejo, Abbe N.; Medsger, Thomas; Feghali-Bostwick, Carol A.

2015-01-01

Objective To evaluate peripheral blood T-helper (TH) cell associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. Methods A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. Results Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. Conclusion This is the first time that multiple cytokines and chemokines have been examined simultaneously LS. In general, a TH-1 (IFN-γ) and TH-17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN–γ signature with elevated IP-10, MCP-1 and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting. PMID:26254121

Understanding Collective Activities of People from Videos.

PubMed

Wongun Choi; Savarese, Silvio

2014-06-01

This paper presents a principled framework for analyzing collective activities at different levels of semantic granularity from videos. Our framework is capable of jointly tracking multiple individuals, recognizing activities performed by individuals in isolation (i.e., atomic activities such as walking or standing), recognizing the interactions between pairs of individuals (i.e., interaction activities) as well as understanding the activities of group of individuals (i.e., collective activities). A key property of our work is that it can coherently combine bottom-up information stemming from detections or fragments of tracks (or tracklets) with top-down evidence. Top-down evidence is provided by a newly proposed descriptor that captures the coherent behavior of groups of individuals in a spatial-temporal neighborhood of the sequence. Top-down evidence provides contextual information for establishing accurate associations between detections or tracklets across frames and, thus, for obtaining more robust tracking results. Bottom-up evidence percolates upwards so as to automatically infer collective activity labels. Experimental results on two challenging data sets demonstrate our theoretical claims and indicate that our model achieves enhances tracking results and the best collective classification results to date.

Shrimp serine proteinase homologues PmMasSPH-1 and -2 play a role in the activation of the prophenoloxidase system.

PubMed

Jearaphunt, Miti; Amparyup, Piti; Sangsuriya, Pakkakul; Charoensapsri, Walaiporn; Senapin, Saengchan; Tassanakajon, Anchalee

2015-01-01

Melanization mediated by the prophenoloxidase (proPO) activating system is a rapid immune response used by invertebrates against intruding pathogens. Several masquerade-like and serine proteinase homologues (SPHs) have been demonstrated to play an essential role in proPO activation in insects and crustaceans. In a previous study, we characterized the masquerade-like SPH, PmMasSPH1, in the black tiger shrimp Penaeus monodon as a multifunctional immune protein based on its recognition and antimicrobial activity against the Gram-negative bacteria Vibrio harveyi. In the present study, we identify a novel SPH, known as PmMasSPH2, composed of an N-terminal clip domain and a C-terminal SP-like domain that share high similarity to those of other insect and crustacean SPHs. We demonstrate that gene silencing of PmMasSPH1 and PmMasSPH2 significantly reduces PO activity, resulting in a high number of V. harveyi in the hemolymph. Interestingly, knockdown of PmMasSPH1 suppressed not only its gene transcript but also other immune-related genes in the proPO system (e.g., PmPPAE2) and antimicrobial peptides (e.g., PenmonPEN3, PenmonPEN5, crustinPm1 and Crus-likePm). The PmMasSPH1 and PmMasSPH2 also show binding activity to peptidoglycan (PGN) of Gram-positive bacteria. Using a yeast two-hybrid analysis and co-immunoprecipitation, we demonstrate that PmMasSPH1 specifically interacted with the final proteinase of the proPO cascade, PmPPAE2. Furthermore, the presence of both PmMasSPH1 and PmPPAE2 enhances PGN-induced PO activity in vitro. Taken together, these results suggest the importance of PmMasSPHs in the activation of the shrimp proPO system.

Shrimp Serine Proteinase Homologues PmMasSPH-1 and -2 Play a Role in the Activation of the Prophenoloxidase System

PubMed Central

Jearaphunt, Miti; Amparyup, Piti; Sangsuriya, Pakkakul; Charoensapsri, Walaiporn; Senapin, Saengchan; Tassanakajon, Anchalee

2015-01-01

Melanization mediated by the prophenoloxidase (proPO) activating system is a rapid immune response used by invertebrates against intruding pathogens. Several masquerade-like and serine proteinase homologues (SPHs) have been demonstrated to play an essential role in proPO activation in insects and crustaceans. In a previous study, we characterized the masquerade-like SPH, PmMasSPH1, in the black tiger shrimp Penaeus monodon as a multifunctional immune protein based on its recognition and antimicrobial activity against the Gram-negative bacteria Vibrio harveyi. In the present study, we identify a novel SPH, known as PmMasSPH2, composed of an N-terminal clip domain and a C-terminal SP-like domain that share high similarity to those of other insect and crustacean SPHs. We demonstrate that gene silencing of PmMasSPH1 and PmMasSPH2 significantly reduces PO activity, resulting in a high number of V. harveyi in the hemolymph. Interestingly, knockdown of PmMasSPH1 suppressed not only its gene transcript but also other immune-related genes in the proPO system (e.g., PmPPAE2) and antimicrobial peptides (e.g., PenmonPEN3, PenmonPEN5, crustinPm1 and Crus-likePm). The PmMasSPH1 and PmMasSPH2 also show binding activity to peptidoglycan (PGN) of Gram-positive bacteria. Using a yeast two-hybrid analysis and co-immunoprecipitation, we demonstrate that PmMasSPH1 specifically interacted with the final proteinase of the proPO cascade, PmPPAE2. Furthermore, the presence of both PmMasSPH1 and PmPPAE2 enhances PGN-induced PO activity in vitro. Taken together, these results suggest the importance of PmMasSPHs in the activation of the shrimp proPO system. PMID:25803442

Neural correlates of active controlled retrieval development: An exploratory ERP study.

PubMed

Simard, France; Cadoret, Geneviève

2018-07-01

Working memory is composed of different processes and encompasses not only the temporary storage of information but also its manipulation in order to perform complex cognitive activities. During childhood, one of these manipulation processes, namely active controlled retrieval, improves significantly between the age of 6 to 10, suggesting that the neuronal network supporting this function undergoes substantial maturational changes. The present study examined the neural activity of 14 healthy children and 14 adults while performing an active controlled retrieval task. Results showed differences in brain activity according to active controlled retrieval in a 300-500 ms window corresponding to the retrieval period. Active controlled retrieval was associated with a P3b-like potential in parietal sites for both children and adults. In fronto-central sites, children demonstrated a "N400 like" potential associated with active retrieval processing. These results are discussed in terms of maturational development. Copyright © 2018 Elsevier Inc. All rights reserved.

Academic Inbreeding and Publication Activities of Russian Faculty

ERIC Educational Resources Information Center

Alipova, Olga; Lovakov, Andrey

2018-01-01

The literature on the consequences of academic inbreeding shows ambiguous results: some papers show that inbreeding positively influences research productivity measured by the quantity and quality of publications, while others demonstrate the opposite effect. There are contradictory results both in the studies of different countries and within…

Laboratory demonstration model: Active cleaning technique device. [for removal of contaminants from an optical surface

NASA Technical Reports Server (NTRS)

Shannon, R. L.; Gillette, R. B.

1974-01-01

The technique which utilizes exposure to a plasma to remove contaminants from a surface was incorporated into a laboratory model which demonstrates active cleaning by both plasma cleaning and ion sputtering modes of operation. The development phase is reported and includes discussion of the plasma tube configuration, device design, and performance tests. A general description of the active cleaning device is provided which includes information on the main power/plasma discharge sensors, and the power, gas supply, and ion accelerator systems. Development of the active cleaning species at high vacuum conditions is described and results indicate that plasma cleaning occurs in the region of a visible plume which extends from the end of the plasma tube. Recommendations are made for research to determine the plasma cleaning mechanism and the plasma species responsible for the cleaning, as well limitations on the type of contaminants that can be removed.

Liquid crystal mediated active nano-plasmonic based on the formation of hybrid plasmonic-photonic modes

NASA Astrophysics Data System (ADS)

Mehrzad, Hossein; Mohajerani, Ezeddin

2018-02-01

The present study aims to demonstrate how active hybrid nano-plasmonic modes become excited due to the coupling of localized plasmonic resonance and Fabry-Perot (FP) optical modes. The proposed structure includes an integration of a micro-cavity filled with liquid crystals with high anisotropy and a layer of gold nanoislands (NIs). The optical absorption of NI is controllably discretized to the narrow-width modes, called "hybrid modes (HM)," due to the interplay between FP and plasmonic modes. HM could demonstrate a strongly intensified and diminished absorption, compared to the absorption of the bare gold layer. Based on the active plasmonic experiments, the HM boosted the figure of merit related to activation capability up to 40 times and subsequently experienced impressive spectral shifts, leading to very wavelength-selective changes. The theoretical simulation of the HM is provided to suggest relevant insights into the experimental results.

Arsenic Removal from Drinking Water by Iron Removal - U.S. EPA Demonstration Project at Big Sauk Lake Mobile Home Park in Sauk Centre, MN Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed and the results obtained from the one-year arsenic removal treatment technology demonstration project at the Big Sauk Lake Mobile Home Park (BSLMHP) in Sauk Centre, MN. The objectives of the project are to evaluate (1) the effective...

Arsenic and Antimony Removal from Drinking Water by Point-of-Entry Reverse Osmosis Coupled with Dual Plumbing Distribution - U.S. EPA Demonstration Project at Carmel Elementary School in Carmel, ME -Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed for and the results obtained from the arsenic and antimony removal treatment technology demonstration project at the Carmel Elementary School (CES) in Carmel, ME. An innovative approach of employing point of entry (POE) reverse osmo...

ARSENIC REMOVAL FROM DRINKING WATER BY POINT-OF-USE (POU) REVERSE OSMOSIS. U.S. EPA DEMONSTRATION PROJECT AT SUNSET RANCH DEVELOPMENT IN HOMEDALE, ID. FINAL PERFORMANCE EVALUATION REPORT

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal technology demonstration project at the Sunset Ranch Development in Homedale, ID. The objectives of the project are to evaluate: 1) the effectiveness of a point of use (POU) re...

Arsenic Removal from Drinking Water by Point of Entry/Point of Use Adsorptive Media U.S. EPA Demonstration Project at Oregon Institute of Technology at Klamath Falls, OR - Final Performance Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the arsenic removal treatment technology demonstration project at Oregon Institute of Technology (OIT) at Klamath Falls, OR. The objectives of the project were to evaluate: (1) the effectiveness...

Physical environment virtualization for human activities recognition

NASA Astrophysics Data System (ADS)

Poshtkar, Azin; Elangovan, Vinayak; Shirkhodaie, Amir; Chan, Alex; Hu, Shuowen

2015-05-01

Human activity recognition research relies heavily on extensive datasets to verify and validate performance of activity recognition algorithms. However, obtaining real datasets are expensive and highly time consuming. A physics-based virtual simulation can accelerate the development of context based human activity recognition algorithms and techniques by generating relevant training and testing videos simulating diverse operational scenarios. In this paper, we discuss in detail the requisite capabilities of a virtual environment to aid as a test bed for evaluating and enhancing activity recognition algorithms. To demonstrate the numerous advantages of virtual environment development, a newly developed virtual environment simulation modeling (VESM) environment is presented here to generate calibrated multisource imagery datasets suitable for development and testing of recognition algorithms for context-based human activities. The VESM environment serves as a versatile test bed to generate a vast amount of realistic data for training and testing of sensor processing algorithms. To demonstrate the effectiveness of VESM environment, we present various simulated scenarios and processed results to infer proper semantic annotations from the high fidelity imagery data for human-vehicle activity recognition under different operational contexts.

Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex.

PubMed

Konermann, Silvana; Brigham, Mark D; Trevino, Alexandro E; Joung, Julia; Abudayyeh, Omar O; Barcena, Clea; Hsu, Patrick D; Habib, Naomi; Gootenberg, Jonathan S; Nishimasu, Hiroshi; Nureki, Osamu; Zhang, Feng

2015-01-29

Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.

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

Kim, Byung Hak; Lee, Jun-Young; Seo, Jee Hee

Nuclear factor (NF)-{kappa}B regulates a central common signaling for immunity and cell survival. Artemisolide (ATM) was previously isolated as a NF-{kappa}B inhibitor from a plant of Artemisia asiatica. However, molecular basis of ATM on NF-{kappa}B activation remains to be defined. Here, we demonstrate that ATM is a typical inhibitor of I{kappa}B kinase {beta} (IKK{beta}), resulting in inhibition of lipopolysaccharide (LPS)-induced NF-{kappa}B activation in RAW 264.7 macrophages. ATM inhibited the kinase activity of highly purified IKK{beta} and also LPS-induced IKK activity in the cells. Moreover, the effect of ATM on IKK{beta} activity was completely abolished by substitution of Cys-179 residue ofmore » IKK{beta} to Ala residue, indicating direct targeting site of ATM. ATM could inhibit I{kappa}B{alpha} phosphorylation in LPS-activated RAW 264.7 cells and subsequently prevent NF-{kappa}B activation. Further, we demonstrate that ATM down-regulates NF-{kappa}B-dependent TNF-{alpha} expression. Taken together, this study provides a pharmacological potential of ATM in NF-{kappa}B-dependent inflammatory disorders.« less

Dusp5 negatively regulates IL-33-mediated eosinophil survival and function

PubMed Central

Holmes, Derek A; Yeh, Jung-Hua; Yan, Donghong; Xu, Min; Chan, Andrew C

2015-01-01

Mitogen-activated protein kinase (MAPK) activation controls diverse cellular functions including cellular survival, proliferation, and apoptosis. Tuning of MAPK activation is counter-regulated by a family of dual-specificity phosphatases (DUSPs). IL-33 is a recently described cytokine that initiates Th2 immune responses through binding to a heterodimeric IL-33Rα (ST2L)/IL-1α accessory protein (IL-1RAcP) receptor that coordinates activation of ERK and NF-κB pathways. We demonstrate here that DUSP5 is expressed in eosinophils, is upregulated following IL-33 stimulation and regulates IL-33 signaling. Dusp5−/− mice have prolonged eosinophil survival and enhanced eosinophil effector functions following infection with the helminth Nippostrongylus brasiliensis. IL-33-activated Dusp5−/− eosinophils exhibit increased cellular ERK1/2 activation and BCL-XL expression that results in enhanced eosinophil survival. In addition, Dusp5−/− eosinophils demonstrate enhanced IL-33-mediated activation and effector functions. Together, these data support a role for DUSP5 as a novel negative regulator of IL-33-dependent eosinophil function and survival. PMID:25398911

Fluorescence-based visualization of autophagic activity predicts mouse embryo viability

NASA Astrophysics Data System (ADS)

Tsukamoto, Satoshi; Hara, Taichi; Yamamoto, Atsushi; Kito, Seiji; Minami, Naojiro; Kubota, Toshiro; Sato, Ken; Kokubo, Toshiaki

2014-03-01

Embryo quality is a critical parameter in assisted reproductive technologies. Although embryo quality can be evaluated morphologically, embryo morphology does not correlate perfectly with embryo viability. To improve this, it is important to understand which molecular mechanisms are involved in embryo quality control. Autophagy is an evolutionarily conserved catabolic process in which cytoplasmic materials sequestered by autophagosomes are degraded in lysosomes. We previously demonstrated that autophagy is highly activated after fertilization and is essential for further embryonic development. Here, we developed a simple fluorescence-based method for visualizing autophagic activity in live mouse embryos. Our method is based on imaging of the fluorescence intensity of GFP-LC3, a versatile marker for autophagy, which is microinjected into the embryos. Using this method, we show that embryonic autophagic activity declines with advancing maternal age, probably due to a decline in the activity of lysosomal hydrolases. We also demonstrate that embryonic autophagic activity is associated with the developmental viability of the embryo. Our results suggest that embryonic autophagic activity can be utilized as a novel indicator of embryo quality.

A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors

NASA Astrophysics Data System (ADS)

Andersson, Patrik; McGuire, Jacqueline; Rubio, Carlos; Gradin, Katarina; Whitelaw, Murray L.; Pettersson, Sven; Hanberg, Annika; Poellinger, Lorenz

2002-07-01

The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding xenobiotic metabolizing enzymes. Known receptor ligands are environmental pollutants including polycyclic aromatic hydrocarbons and polychlorinated dioxins. Loss-of-function (gene-disruption) studies in mice have demonstrated that the AhR is involved in toxic effects of dioxins but have not yielded unequivocal results concerning the physiological function of the receptor. Gain-of-function studies therefore were performed to unravel the biological functions of the AhR. A constitutively active AhR expressed in transgenic mice reduced the life span of the mice and induced tumors in the glandular part of the stomach, demonstrating the oncogenic potential of the AhR and implicating the receptor in regulation of cell proliferation.

AMF/PGI transactivates the MMP-3 gene through the activation of Src-RhoA-phosphatidylinositol 3-kinase signaling to induce hepatoma cell migration.

PubMed

Shih, Wen-Ling; Liao, Ming-Huei; Yu, Feng-Ling; Lin, Ping-Yuan; Hsu, Hsue-Yin; Chiu, Shu-Jun

2008-11-08

We have previously shown that AMF/PGI induces hepatoma cell migration through the induction of MMP-3. This work investigates how AMF/PGI activates the MMP-3 gene. We demonstrated that AMF/PGI transactivates the MMP-3 gene promoter through AP-1. The transactivation and induction of cell migration effect of AMF/PGI directly correlates with its enzymatic activity. Various analyses showed that AMF/PGI stimulated the Src-RhoA-PI3-kinase signaling pathway, and these three signaling molecules could form a complex. Our results demonstrate a new mechanism of AMF/PGI-induced cell migration and a link between Src-RhoA-PI3-kinase, AP-1, MMP-3 and hepatoma cell migration.

Multi-walled carbon nanotubes increase anxiety levels in rats and reduce exploratory activity in the open field test.

PubMed

Sayapina, N V; Batalova, T A; Chaika, V V; Kuznetsov, V L; Sergievich, A A; Kolosov, V P; Perel'man, Yu M; Golokhvast, K S

2015-01-01

The results of the first study on the effects of multi-walled carbon nanotubes (MWNTs) on the exploratory activity and the emotional state in laboratory rats assessed by the open field test are reported. During three or ten days, rats received 8-10 nm MWNTs added to their food at a dose of 500 mg/kg. It was demonstrated that, in the group of rats which were fed with MWNTs, the integrated anxiety level index began to increase as early as the third day of the experiment; on the tenth day, it appeared to be twice increased. It was also demonstrated that MWNTs decreased the integrated exploratory activity index nearly twofold on the third day and nearly fourfold on the tenth day.

Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes.

PubMed

Gormand, Amélie; Henriksson, Emma; Ström, Kristoffer; Jensen, Thomas Elbenhardt; Sakamoto, Kei; Göransson, Olga

2011-05-01

AMP-activated protein kinase (AMPK) is a serine/threonine kinase that regulates cellular and whole body energy homeostasis. In adipose tissue, activation of AMPK has been demonstrated in response to a variety of extracellular stimuli. However, the upstream kinase that activates AMPK in adipocytes remains elusive. Previous studies have identified LKB1 as a major AMPK kinase in muscle, liver, and other tissues. In certain cell types, Ca(2+) /calmodulin-dependent protein kinase kinase β (CaMKKβ) has been shown to activate AMPK in response to increases of intracellular Ca(2+) levels. Our aim was to investigate if LKB1 and/or CaMKK function as AMPK kinases in adipocytes. We used adipose tissue and isolated adipocytes from mice in which the expression of LKB1 was reduced to 10-20% of that of wild-type (LKB1 hypomorphic mice). We show that adipocytes from LKB1 hypomorphic mice display a 40% decrease in basal AMPK activity and a decrease of AMPK activity in the presence of the AMPK activator phenformin. We also demonstrate that stimulation of 3T3L1 adipocytes with intracellular [Ca(2+) ]-raising agents results in an activation of the AMPK pathway. The inhibition of CaMKK isoforms, particularly CaMKKβ, by the inhibitor STO-609 or by siRNAs, blocked Ca(2+) -, but not phenformin-, AICAR-, or forskolin-induced activation of AMPK, indicating that CaMKK activated AMPK in response to Ca(2+) . Collectively, we show that LKB1 is required to maintain normal AMPK-signaling in non-stimulated adipocytes and in the presence of phenformin. In addition, we demonstrate the existence of a Ca(2+) /CaMKK signaling pathway that can also regulate the activity of AMPK in adipocytes. Copyright © 2011 Wiley-Liss, Inc.

The unexploded ordnance (UXO) contamination problem and the state of the art of UXO remediation technologies

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

Thomsen, K.O.; Richardson, C.B.; Valder, K.M.

1996-12-31

Millions of acres of US government property are contaminated with unexploded ordnance (UXO) as a result of weapons system testing and troop training activities conducted over the past century at Department of Defense (DoD) sites. Recent DoD downsizing has resulted in the closing of many military bases, many of which are contaminated with UXO. One unexpected result of DoD`s downsizing is the attention focused on the unique problems associated with UXO remediation at these closed military bases. The U.S. Army Environmental Center (U SAEC) is the lead DoD agency for UXO clearance technology demonstrations, evaluation, and technology transfer. USAEC directedmore » the Naval Explosive Ordnance Disposal Technology Division (NAVEODTECHDIV) to serve as the technical lead for the advanced technology demonstration (ATD) program. In 1994, USAEC and NAVEODTECHDIV created controlled test facilities at the U.S. Army Jefferson Proving Ground in Madison, Indiana, to demonstrate and evaluate commercial UXO clearance systems and technologies. Phase I controlled site demonstrations were conducted during the summer of 1994. These demonstrations were followed by the Phase II controlled site demonstrations at JPG. This paper presents the results of the Phase II controlled site demonstrations. The overall performance of the demonstrators is presented along with the operational characteristics and limitations of the various systems and technologies evaluated. Individual demonstrator performance statistics are evaluated by sensor type and sensor transport method.« less

Comparison between active (pumped) and passive (diffusive) sampling methods for formaldehyde in pathology and histology laboratories.

PubMed

Lee, Eun Gyung; Magrm, Rana; Kusti, Mohannad; Kashon, Michael L; Guffey, Steven; Costas, Michelle M; Boykin, Carie J; Harper, Martin

2017-01-01

This study was to determine occupational exposures to formaldehyde and to compare concentrations of formaldehyde obtained by active and passive sampling methods. In one pathology and one histology laboratories, exposure measurements were collected with sets of active air samplers (Supelco LpDNPH tubes) and passive badges (ChemDisk Aldehyde Monitor 571). Sixty-six sample pairs (49 personal and 17 area) were collected and analyzed by NIOSH NMAM 2016 for active samples and OSHA Method 1007 (using the manufacturer's updated uptake rate) for passive samples. All active and passive 8-hr time-weighted average (TWA) measurements showed compliance with the OSHA permissible exposure limit (PEL-0.75 ppm) except for one passive measurement, whereas 78% for the active and 88% for the passive samples exceeded the NIOSH recommended exposure limit (REL-0.016 ppm). Overall, 73% of the passive samples showed higher concentrations than the active samples and a statistical test indicated disagreement between two methods for all data and for data without outliers. The OSHA Method cautions that passive samplers should not be used for sampling situations involving formalin solutions because of low concentration estimates in the presence of reaction products of formaldehyde and methanol (a formalin additive). However, this situation was not observed, perhaps because the formalin solutions used in these laboratories included much less methanol (3%) than those tested in the OSHA Method (up to 15%). The passive samplers in general overestimated concentrations compared to the active method, which is prudent for demonstrating compliance with an occupational exposure limit, but occasional large differences may be a result of collecting aerosolized droplets or splashes on the face of the samplers. In the situations examined in this study the passive sampler generally produces higher results than the active sampler so that a body of results from passive samplers demonstrating compliance with the OSHA PEL would be a valid conclusion. However, individual passive samples can show lower results than a paired active sampler so that a single result should be treated with caution.

The Moderating Effect of Personality Type on the Relationship between Leisure Activity and Executive Control in Older Adults

PubMed Central

Hill, Nikki L.; Lin, Feng Vankee; Parisi, Jeanine M.; Kolanowski, Ann

2016-01-01

We examined the moderating effect of personality on the association between leisure activities and executive control in healthy community-dwelling older adults. We found two distinct personality typologies: individuals with a Resilient personality were characterized by emotional stability and self-confidence; whereas, those who resembled an Overcontrolled personality tended to be introverted, but also low on neuroticism. Resilient individuals were more likely than Overcontrolled individuals to demonstrate higher executive function and attention as a result of participation in mental activities. These results suggest that personality might be important to include in studies that test the efficacy of activity interventions for improving cognition. PMID:27087715

Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

PubMed Central

Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

2015-01-01

Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner.

PubMed

Conos, Stephanie A; Chen, Kaiwen W; De Nardo, Dominic; Hara, Hideki; Whitehead, Lachlan; Núñez, Gabriel; Masters, Seth L; Murphy, James M; Schroder, Kate; Vaux, David L; Lawlor, Kate E; Lindqvist, Lisa M; Vince, James E

2017-02-07

Necroptosis is a physiological cell suicide mechanism initiated by receptor-interacting protein kinase-3 (RIPK3) phosphorylation of mixed-lineage kinase domain-like protein (MLKL), which results in disruption of the plasma membrane. Necroptotic cell lysis, and resultant release of proinflammatory mediators, is thought to cause inflammation in necroptotic disease models. However, we previously showed that MLKL signaling can also promote inflammation by activating the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome to recruit the adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and trigger caspase-1 processing of the proinflammatory cytokine IL-1β. Here, we provide evidence that MLKL-induced activation of NLRP3 requires (i) the death effector four-helical bundle of MLKL, (ii) oligomerization and association of MLKL with cellular membranes, and (iii) a reduction in intracellular potassium concentration. Although genetic or pharmacological targeting of NLRP3 or caspase-1 prevented MLKL-induced IL-1β secretion, they did not prevent necroptotic cell death. Gasdermin D (GSDMD), the pore-forming caspase-1 substrate required for efficient NLRP3-triggered pyroptosis and IL-1β release, was not essential for MLKL-dependent death or IL-1β secretion. Imaging of MLKL-dependent ASC speck formation demonstrated that necroptotic stimuli activate NLRP3 cell-intrinsically, indicating that MLKL-induced NLRP3 inflammasome formation and IL-1β cleavage occur before cell lysis. Furthermore, we show that necroptotic activation of NLRP3, but not necroptotic cell death alone, is necessary for the activation of NF-κB in healthy bystander cells. Collectively, these results demonstrate the potential importance of NLRP3 inflammasome activity as a driving force for inflammation in MLKL-dependent diseases.

Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner

PubMed Central

Conos, Stephanie A.; Hara, Hideki; Whitehead, Lachlan; Núñez, Gabriel; Masters, Seth L.; Murphy, James M.; Schroder, Kate; Vaux, David L.; Lawlor, Kate E.; Vince, James E.

2017-01-01

Necroptosis is a physiological cell suicide mechanism initiated by receptor-interacting protein kinase-3 (RIPK3) phosphorylation of mixed-lineage kinase domain-like protein (MLKL), which results in disruption of the plasma membrane. Necroptotic cell lysis, and resultant release of proinflammatory mediators, is thought to cause inflammation in necroptotic disease models. However, we previously showed that MLKL signaling can also promote inflammation by activating the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome to recruit the adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and trigger caspase-1 processing of the proinflammatory cytokine IL-1β. Here, we provide evidence that MLKL-induced activation of NLRP3 requires (i) the death effector four-helical bundle of MLKL, (ii) oligomerization and association of MLKL with cellular membranes, and (iii) a reduction in intracellular potassium concentration. Although genetic or pharmacological targeting of NLRP3 or caspase-1 prevented MLKL-induced IL-1β secretion, they did not prevent necroptotic cell death. Gasdermin D (GSDMD), the pore-forming caspase-1 substrate required for efficient NLRP3-triggered pyroptosis and IL-1β release, was not essential for MLKL-dependent death or IL-1β secretion. Imaging of MLKL-dependent ASC speck formation demonstrated that necroptotic stimuli activate NLRP3 cell-intrinsically, indicating that MLKL-induced NLRP3 inflammasome formation and IL-1β cleavage occur before cell lysis. Furthermore, we show that necroptotic activation of NLRP3, but not necroptotic cell death alone, is necessary for the activation of NF-κB in healthy bystander cells. Collectively, these results demonstrate the potential importance of NLRP3 inflammasome activity as a driving force for inflammation in MLKL-dependent diseases. PMID:28096356

HER1 signaling mediates extravillous trophoblast differentiation in humans.

PubMed

Wright, J K; Dunk, C E; Amsalem, H; Maxwell, C; Keating, S; Lye, S J

2010-12-01

This study examines the role of HER1 signaling in the differentiation of proliferative extravillous trophoblast (EVT) into invasive EVT. Using the JAR choriocarcinoma cell line and placental villous explants as experimental models and immunohistochemical assessment of protein markers of EVT differentiation (downregulation of HER1 and Cx40 and upregulation of HER2 and alpha1 integrin), we show that the ability of decidual conditioned medium (DCM) to induce HER1/2 switching was abrogated in the presence of the HER1 antagonist, AG1478. Similarly, epidermal growth factor (EGF) treatment resulted in the downregulation of HER1 and an upregulation of HER2 expression, whereas co-incubation of EGF with AG1478 inhibited this response. However, EGF did not downregulate Cx40 or induce migration of EVT. In contrast, heparin-binding epidermal-like growth factor (HBEGF) stimulated dose-dependent JAR cell migration, which was inhibited by both AG1478 and AG825 (HER2 antagonist). Western blot analysis of HER1 activation demonstrated that HBEGF-mediated phosphorylation of the HER1 Tyr992 and Tyr1068 sites, while EGF activated the Tyr1045 site. Moreover, HBEGF induced a stronger and more sustained activation of both the mitogen-activated protein kinase and phosphoinositol 3 kinase (PIK3) signaling pathways. Migration assays using a panel of signaling pathway inhibitors demonstrated that the HBEGF-mediated migration was dependent on the PIK3 pathway. These results demonstrate that HBEGF-mediated HER1 signaling through PIK3 is an important component of EVT invasion.

Final payload test results for the RemoveDebris active debris removal mission

NASA Astrophysics Data System (ADS)

Forshaw, Jason L.; Aglietti, Guglielmo S.; Salmon, Thierry; Retat, Ingo; Roe, Mark; Burgess, Christopher; Chabot, Thomas; Pisseloup, Aurélien; Phipps, Andy; Bernal, Cesar; Chaumette, François; Pollini, Alexandre; Steyn, Willem H.

2017-09-01

Since the beginning of the space era, a significant amount of debris has progressively been generated in space. Active Debris Removal (ADR) missions have been suggested as a way of limiting and controlling future growth in orbital space debris by actively deploying vehicles to remove debris. The European Commission FP7-sponsored RemoveDebris mission, which started in 2013, draws on the expertise of some of Europe's most prominent space institutions in order to demonstrate key ADR technologies in a cost effective ambitious manner: net capture, harpoon capture, vision-based navigation, dragsail de-orbiting. This paper provides an overview of some of the final payload test results before launch. A comprehensive test campaign is underway on both payloads and platform. The tests aim to demonstrate both functional success of the experiments and that the experiments can survive the space environment. Space environmental tests (EVT) include vibration, thermal, vacuum or thermal-vacuum (TVAC) and in some cases EMC and shock. The test flow differs for each payload and depends on the heritage of the constituent payload parts. The paper will also provide an update to the launch, expected in 2017 from the International Space Station (ISS), and test philosophy that has been influenced from the launch and prerequisite NASA safety review for the mission. The RemoveDebris mission aims to be one of the world's first in-orbit demonstrations of key technologies for active debris removal and is a vital prerequisite to achieving the ultimate goal of a cleaner Earth orbital environment.

Poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings facilitate smaller neural recording electrodes

NASA Astrophysics Data System (ADS)

Ludwig, Kip A.; Langhals, Nicholas B.; Joseph, Mike D.; Richardson-Burns, Sarah M.; Hendricks, Jeffrey L.; Kipke, Daryl R.

2011-02-01

We investigated using poly(3,4-ethylenedioxythiophene) (PEDOT) to lower the impedance of small, gold recording electrodes with initial impedances outside of the effective recording range. Smaller electrode sites enable more densely packed arrays, increasing the number of input and output channels to and from the brain. Moreover, smaller electrode sizes promote smaller probe designs; decreasing the dimensions of the implanted probe has been demonstrated to decrease the inherent immune response, a known contributor to the failure of long-term implants. As expected, chronically implanted control electrodes were unable to record well-isolated unit activity, primarily as a result of a dramatically increased noise floor. Conversely, electrodes coated with PEDOT consistently recorded high-quality neural activity, and exhibited a much lower noise floor than controls. These results demonstrate that PEDOT coatings enable electrode designs 15 µm in diameter.

Four experimental demonstrations of active vibration control for flexible structures

NASA Technical Reports Server (NTRS)

Phillips, Doug; Collins, Emmanuel G., Jr.

1990-01-01

Laboratory experiments designed to test prototype active-vibration-control systems under development for future flexible space structures are described, summarizing previously reported results. The control-synthesis technique employed for all four experiments was the maximum-entropy optimal-projection (MEOP) method (Bernstein and Hyland, 1988). Consideration is given to: (1) a pendulum experiment on large-amplitude LF dynamics; (2) a plate experiment on broadband vibration suppression in a two-dimensional structure; (3) a multiple-hexagon experiment combining the factors studied in (1) and (2) to simulate the complexity of a large space structure; and (4) the NASA Marshall ACES experiment on a lightweight deployable 45-foot beam. Extensive diagrams, drawings, graphs, and photographs are included. The results are shown to validate the MEOP design approach, demonstrating that good performance is achievable using relatively simple low-order decentralized controllers.

Heterogeneous engineered cartilage growth results from gradients of media-supplemented active TGF-β and is ameliorated by the alternative supplementation of latent TGF-β.

PubMed

Albro, Michael B; Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Shim, Jay J; Vunjak-Novakovic, Gordana; Hung, Clark T; Ateshian, Gerard A

2016-01-01

Transforming growth factor beta (TGF-β) has become one of the most widely utilized mediators of engineered cartilage growth. It is typically exogenously supplemented in the culture medium in its active form, with the expectation that it will readily transport into tissue constructs through passive diffusion and influence cellular biosynthesis uniformly. The results of this investigation advance three novel concepts regarding the role of TGF-β in cartilage tissue engineering that have important implications for tissue development. First, through the experimental and computational analysis of TGF-β concentration distributions, we demonstrate that, contrary to conventional expectations, media-supplemented exogenous active TGF-β exhibits a pronounced concentration gradient in tissue constructs, resulting from a combination of high-affinity binding interactions and a high cellular internalization rate. These gradients are sustained throughout the entire culture duration, leading to highly heterogeneous tissue growth; biochemical and histological measurements support that while biochemical content is enhanced up to 4-fold at the construct periphery, enhancements are entirely absent beyond 1 mm from the construct surface. Second, construct-encapsulated chondrocytes continuously secrete large amounts of endogenous TGF-β in its latent form, a portion of which undergoes cell-mediated activation and enhances biosynthesis uniformly throughout the tissue. Finally, motivated by these prior insights, we demonstrate that the alternative supplementation of additional exogenous latent TGF-β enhances biosynthesis uniformly throughout tissue constructs, leading to enhanced but homogeneous tissue growth. This novel demonstration suggests that latent TGF-β supplementation may be utilized as an important tool for the translational engineering of large cartilage constructs that will be required to repair the large osteoarthritic defects observed clinically. Copyright © 2015. Published by Elsevier Ltd.

Heterogeneous engineered cartilage growth results from gradients of media-supplemented active TGF-β and is ameliorated by the alternative supplementation of latent TGF-β

PubMed Central

Durney, Krista M.; Cigan, Alexander D.; Shim, Jay J.; Vunjak-Novakovic, Gordana; Hung, Clark T.; Ateshian, Gerard A.

2016-01-01

Transforming growth factor beta (TGF-β) has become one of the most widely utilized mediators of engineered cartilage growth. It is typically exogenously supplemented in the culture medium in its active form, with the expectation that it will readily transport into tissue constructs through passive diffusion and influence cellular biosynthesis uniformly. The results of this investigation advance three novel concepts regarding the role of TGF-β in cartilage tissue engineering that have important implications for tissue development. First, through the experimental and computational analysis of TGF-β concentration distributions, we demonstrate that, contrary to conventional expectations, media-supplemented exogenous active TGF-β exhibits a pronounced concentration gradient in tissue constructs, resulting from a combination of high-affinity binding interactions and a high cellular internalization rate. These gradients are sustained throughout the entire culture duration, leading to highly heterogeneous tissue growth; biochemical and histological measurements support that while biochemical content is enhanced up to 4-fold at the construct periphery, enhancements are entirely absent beyond 1 mm from the construct surface. Second, construct-encapsulated chondrocytes continuously secrete large amounts of endogenous TGF-β in its latent form, a portion of which undergoes cell-mediated activation and enhances biosynthesis uniformly throughout the tissue. Finally, motivated by these prior insights, we demonstrate that the alternative supplementation of additional exogenous latent TGF-β enhances biosynthesis uniformly throughout tissue constructs, leading to enhanced but homogeneous tissue growth. This novel demonstration suggests that latent TGF-β supplementation may be utilized as an important tool for the translational engineering of large cartilage constructs that will be required to repair the large osteoarthritic defects observed clinically. PMID:26599624

Enhanced efficacy and sensory properties of an anti-dandruff shampoo containing zinc pyrithione and climbazole.

PubMed

Turner, G A; Matheson, J R; Li, G-Z; Fei, X-Q; Zhu, D; Baines, F L

2013-02-01

Dandruff is a common complaint and is suffered by as much as half of the population at some time post puberty. The condition is characterized by the presence of flakes on the scalp and in the hair, and is often accompanied by itch. The most common treatment for dandruff is the use of shampoo formulations that contain fungistatic agents such as zinc pyrithione (ZPT) and octopirox. Whilst most antidandruff shampoos are effective in resolving the symptoms of dandruff these shampoos can often result in hair condition that is less than acceptable to consumers which can lead to a tendency for them to revert to use of a non-antidandruff shampoo. This can result in a rapid return of dandruff symptoms. The aim of this investigation was to study the impact of using a combination of antidandruff actives and silicones on the resolution of dandruff and to deliver superior sensory properties to the hair. We have demonstrated that shampoo containing the dual active system of ZPT/Climbazole deposits both active agents onto a model skin surface (VitroSkin) and reduces Malassezia furfur regrowth in vitro. Clinical evaluation of the dual active shampoo demonstrated superior efficacy and retained superiority during a regression phase where all subjects reverted to using a non-antidandruff shampoo. We have also demonstrated that it is possible to deposit silicone materials from antidandruff shampoo uniformly over both virgin and damaged hair fibres that results in smoother hair fibres (as evidenced by reduced dry friction). This combination of antidandruff agents and conditioning silicones delivered from a shampoo provides subjects with superior antidandruff efficacy and desired end sensory benefits ensuring compliance and longer term dandruff removal. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein.

PubMed

Xiao, G; Sun, S C

2000-10-26

Human T-cell leukemia virus type I (HTLV-I) Tax protein persistently stimulates the activity of IkappaB kinase (IKK), resulting in constitutive activation of the transcription factor NF-kappaB. Tax activation of IKK requires physical interaction of this viral protein with the IKK regulatory subunit, IKKgamma. The Tax/IKKgamma interaction allows Tax to engage the IKK catalytic subunits, IKKalpha and IKKbeta, although it remains unclear whether this linker function of IKKgamma is sufficient for supporting the Tax-specific IKK activation. To address this question, we have examined the sequences of IKKgamma required for modulating the Tax/IKK signaling. We demonstrate that when fused to Tax, a small N-terminal fragment of IKKgamma, containing its minimal IKKalpha/beta-binding domain, is sufficient for bringing Tax to and activating the IKK catalytic subunits. Disruption of the IKKalpha/beta-binding activity of this domain abolishes its function in modulating the Tax/IKK signaling. We further demonstrate that direct fusion of Tax to IKKalpha and IKKbeta leads to activation of these kinases. These findings suggest that the IKKgamma-directed Tax/IKK association serves as a molecular trigger for IKK activation.

Separation of Bombyxin from a neuropeptide of Bombyx mori showing Summer-morph-producing Hormone (SMPH) activity in the Asian Comma Butterfly, Polygonia c-aureum L.

PubMed

Endo, K; Yamanaka, A; Mitsumasu, K; Sakurama, T; Tanaka, D

1997-02-21

A neuropeptide from brain-suboesophageal ganglion (Br-SG) complexes of the silkmoth, Bombyx mori, shows summer-morph-producing hormone (SMPH) activity in the Asian comma butterfly, P. c-aureum. The SMPH-active peptide was extracted and demonstrated to be almost the same molecular size as bombyxin (4-5kD), a nueropeptide which shows prothoracicotropic hormone (PTTH) activity when assayed in vitro with prothoracic glands (PGs) of 4th-instar B. mori larvae in vitro. A Sephadex G-50 fraction of 3-8kD molecules prepared from Br-SG complexes of B. mori adults was applied to CM-, SP-, DEAE- or QAE- Toyoperal columns at pH 5.6 (or pH 6.9). The SMPH-activity could be separated from the PTTH-activity (or bombyxin) by subjecting a SMPH- and PTTH-active preparation of B. mori to anion-exchange chromatography at pH 6.9. By reversed-phase HPLC following an anion-exchange chromatography, SMPH-activity was recovered in two fractions of 40-45% acetonitril. Results demonstrate that the B. mori peptide showing the SMPH-activity in P. c-aureum is a different molecule than bombyxin.

Evidence of an inflammatory-like response in non-normally pigmented tissues of two scleractinian corals

PubMed Central

Palmer, Caroline V; Mydlarz, Laura D; Willis, Bette L

2008-01-01

Increasing evidence of links between climate change, anthropogenic stress and coral disease underscores the importance of understanding the mechanisms by which reef-building corals resist infection and recover from injury. Cellular inflammation and melanin-producing signalling pathway are two mechanisms employed by invertebrates to remove foreign organisms such as pathogens, but they have not been recorded previously in scleractinian corals. This study demonstrates the presence of the phenoloxidase (PO) activating melanin pathway in two species of coral, Acropora millepora and a massive species of Porites, which both develop local pigmentation in response to interactions with a variety of organisms. l-DOPA (3-(3,4-dihydroxyphenyl)-l-alanine) substrate-based enzyme activation assays demonstrated PO activity in healthy tissues of both species and upregulation in pigmented tissues of A. millepora. Histological staining conclusively identified the presence of melanin in Porites tissues. These results demonstrate that the PO pathway is active in both coral species. Moreover, the upregulation of PO activity in areas of non-normal pigmentation in A. millepora and increased melanin production in pigmented Porites tissues suggest the presence of a generalized defence response to localized stress. Interspecific differences in the usage of pathways involved in innate immunity may underlie the comparative success of massive Porites sp. as long-lived stress tolerators. PMID:18700208

Prevalence and Mechanisms of Dynamic Chemical Defenses in Tropical Sponges

PubMed Central

Rohde, Sven; Nietzer, Samuel; Schupp, Peter J.

2015-01-01

Sponges and other sessile invertebrates are lacking behavioural escape or defense mechanisms and rely therefore on morphological or chemical defenses. Studies from terrestrial systems and marine algae demonstrated facultative defenses like induction and activation to be common, suggesting that sessile marine organisms also evolved mechanisms to increase the efficiency of their chemical defense. However, inducible defenses in sponges have not been investigated so far and studies on activated defenses are rare. We investigated whether tropical sponge species induce defenses in response to artificial predation and whether wounding triggers defense activation. Additionally, we tested if these mechanisms are also used to boost antimicrobial activity to avoid bacterial infection. Laboratory experiments with eight pacific sponge species showed that 87% of the tested species were chemically defended. Two species, Stylissa massa and Melophlus sarasinorum, induced defenses in response to simulated predation, which is the first demonstration of induced antipredatory defenses in marine sponges. One species, M. sarasinorum, also showed activated defense in response to wounding. Interestingly, 50% of the tested sponge species demonstrated induced antimicrobial defense. Simulated predation increased the antimicrobial defenses in Aplysinella sp., Cacospongia sp., M. sarasinorum, and S. massa. Our results suggest that wounding selects for induced antimicrobial defenses to protect sponges from pathogens that could otherwise invade the sponge tissue via feeding scars. PMID:26154741

Decoding intravesical pressure from local field potentials in rat lumbosacral spinal cord

NASA Astrophysics Data System (ADS)

Im, Changkyun; Park, Hae Yong; Koh, Chin Su; Ryu, Sang Baek; Seo, In Seok; Kim, Yong Jung; Kim, Kyung Hwan; Shin, Hyung-Cheul

2016-10-01

Chronic monitoring of intravesical pressure is required to detect the onset of intravesical hypertension and the progression of a more severe condition. Recent reports demonstrate the bladder state can be monitored from the spiking activity of the dorsal root ganglia or lumbosacral spinal cord. However, one of the most serious challenges for these methods is the difficulty of sustained spike signal acquisition due to the high-electrode-location-sensitivity of spikes or neuro-degeneration. Alternatively, it has been demonstrated that local field potential recordings are less affected by encapsulation reactions or electrode location changes. Here, we hypothesized that local field potential (LFP) from the lumbosacral dorsal horn may provide information concerning the intravesical pressure. LFP and spike activities were simultaneously recorded from the lumbosacral spinal cord of anesthetized rats during bladder filling. The results show that the LFP activities carry significant information about intravesical pressure along with spiking activities. Importantly, the intravesical pressure is decoded from the power in high-frequency bands (83.9-256 Hz) with a substantial performance similar to that of the spike train decoding. These findings demonstrate that high-frequency LFP activity can be an alternative intravesical pressure monitoring signal, which could lead to a proper closed loop system for urinary control.

Structure-activity relationships of rationally designed AMACR 1A inhibitors.

PubMed

Yevglevskis, Maksims; Lee, Guat L; Nathubhai, Amit; Petrova, Yoana D; James, Tony D; Threadgill, Michael D; Woodman, Timothy J; Lloyd, Matthew D

2018-04-30

α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the 'racemisation' reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no structure-activity relationship study has been performed. This paper describes the first structure-activity relationship study, in which a series of 23 known and potential rational AMACR inhibitors were evaluated. AMACR was potently inhibited (IC 50  = 400-750 nM) by ibuprofenoyl-CoA and derivatives. Potency was positively correlated with inhibitor lipophilicity. AMACR was also inhibited by straight-chain and branched-chain acyl-CoA esters, with potency positively correlating with inhibitor lipophilicity. 2-Methyldecanoyl-CoAs were ca. 3-fold more potent inhibitors than decanoyl-CoA, demonstrating the importance of the 2-methyl group for effective inhibition. Elimination substrates and compounds with modified acyl-CoA cores were also investigated, and shown to be potent inhibitors. These results are the first to demonstrate structure-activity relationships of rational AMACR inhibitors and that potency can be predicted by acyl-CoA lipophilicity. The study also demonstrates the utility of the colorimetric assay for thorough inhibitor characterisation. Copyright © 2018 Elsevier Inc. All rights reserved.

Nucleotide Catabolism on the Surface of Aortic Valve Xenografts; Effects of Different Decellularization Strategies.

PubMed

Kutryb-Zajac, Barbara; Yuen, Ada H Y; Khalpey, Zain; Zukowska, Paulina; Slominska, Ewa M; Taylor, Patricia M; Goldstein, Steven; Heacox, Albert E; Lavitrano, Marialuisa; Chester, Adrian H; Yacoub, Magdi H; Smolenski, Ryszard T

2016-04-01

Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to <10 %. Detergent decellularization completely removed (<5 %) all these activities. These results demonstrate high intensity of extracellular nucleotide metabolism on valve surface and indicate that various valve decellularization techniques differently affect ecto-enzyme activities that could be important in the development of improved valve prostheses.

A novel label-free fluorescence strategy for methyltransferase activity assay based on dsDNA-templated copper nanoparticles coupled with an endonuclease-assisted signal transduction system.

PubMed

Lai, Q Q; Liu, M D; Gu, C C; Nie, H G; Xu, X J; Li, Z H; Yang, Z; Huang, S M

2016-02-21

Evaluating DNA methyltransferase (MTase) activity has received considerable attention due to its significance in the fields of early cancer clinical diagnostics and drug discovery. Herein, we proposed a novel label-free fluorescence method for MTase activity assay by coupling double-stranded DNA (dsDNA)-templated copper nanoparticles (CuNPs) with an endonuclease-assisted signal transduction system. In this strategy, dsDNA molecules were first methylated by DNA adenine methylation (Dam) MTase and then cleaved by the methylation-sensitive restriction endonuclease DpnI. The cleaved DNA fragments could not act as efficient templates for the formation of fluorescent CuNPs and thus no fluorescence signal was produced. Under optimized experimental conditions, the developed strategy exhibited a sensitive fluorescence response to Dam MTase activity. This strategy was also demonstrated to provide an excellent platform to the inhibitor screening for Dam MTase. These results demonstrated the great potential for the practical applications of the proposed strategy for Dam MTase activity assay.

Nicotinamide Inhibits the Lysosomal Cathepsin b-like Protease and Kills African Trypanosomes*

PubMed Central

Unciti-Broceta, Juan D.; Maceira, José; Morales, Sonia; García-Pérez, Angélica; Muñóz-Torres, Manuel E.; Garcia-Salcedo, Jose A.

2013-01-01

Nicotinamide, a soluble compound of the vitamin B3 group, has antimicrobial activity against several microorganisms ranging from viruses to parasite protozoans. However, the mode of action of this antimicrobial activity is unknown. Here, we investigate the trypanocidal activity of nicotinamide on Trypanosoma brucei, the causative agent of African trypanosomiasis. Incubation of trypanosomes with nicotinamide causes deleterious defects in endocytic traffic, disruption of the lysosome, failure of cytokinesis, and, ultimately, cell death. At the same concentrations there was no effect on a cultured mammalian cell line. The effects on endocytosis and vesicle traffic were visible within 3 h and can be attributed to inhibition of lysosomal cathepsin b-like protease activity. The inhibitory effect of nicotinamide was confirmed by a direct activity assay of recombinant cathepsin b-like protein. Taken together, these data demonstrate that inhibition of the lysosomal protease cathepsin b-like blocks endocytosis, causing cell death. In addition, these results demonstrate for the first time the inhibitory effect of nicotinamide on a protease. PMID:23443665

ROCK1 in AgRP neurons regulates energy expenditure and locomotor activity in male mice.

PubMed

Huang, Hu; Lee, Seung Hwan; Ye, Chianping; Lima, Ines S; Oh, Byung-Chul; Lowell, Bradford B; Zabolotny, Janice M; Kim, Young-Bum

2013-10-01

Normal leptin signaling is essential for the maintenance of body weight homeostasis. Proopiomelanocortin- and agouti-related peptide (AgRP)-producing neurons play critical roles in regulating energy metabolism. Our recent work demonstrates that deletion of Rho-kinase 1 (ROCK1) in the AgRP neurons of mice increased body weight and adiposity. Here, we report that selective loss of ROCK1 in AgRP neurons caused a significant decrease in energy expenditure and locomotor activity of mice. These effects were independent of any change in food intake. Furthermore, AgRP neuron-specific ROCK1-deficient mice displayed central leptin resistance, as evidenced by impaired Signal Transducer and Activator of Transcription 3 activation in response to leptin administration. Leptin's ability to hyperpolarize and decrease firing rate of AgRP neurons was also abolished in the absence of ROCK1. Moreover, diet-induced and genetic forms of obesity resulted in reduced ROCK1 activity in murine arcuate nucleus. Of note, high-fat diet also impaired leptin-stimulated ROCK1 activity in arcuate nucleus, suggesting that a defect in hypothalamic ROCK1 activity may contribute to the pathogenesis of central leptin resistance in obesity. Together, these data demonstrate that ROCK1 activation in hypothalamic AgRP neurons is required for the homeostatic regulation of energy expenditure and adiposity. These results further support previous work identifying ROCK1 as a key regulator of energy balance and suggest that targeting ROCK1 in the hypothalamus may lead to development of antiobesity therapeutics.

Omani propolis: chemical profiling, antibacterial activity and new propolis plant sources

PubMed Central

2013-01-01

Background Propolis (bee glue) is a resinous honeybee product having a long history of application in many countries as a traditional remedy for treating wounds, burns, soar throat, stomach disorders, etc. It has been proved to possess beneficial biological effects, including antimicrobial, antioxidant, anti-inflammatory, cytotoxic, antiulcer, and many others. Bees gather propolis from diverse resinous plant parts and in different phytogeographic regions its chemical composition might vary significantly. In this article we report the results of the first study on the chemical profiles of propolis from Oman, its plant origin and antibacterial activity. Results The chemical profiles of Omani propolis extracts were obtained by GC-MS analysis after silylation. Over 50 individual compounds were identified in the samples, belonging to different compound types: sugars, polyols, hydroxy acids, fatty acids, cardanols and cardols, anacardic acids, flavan derivatives, triterpenes, prenylated flavanones and chalcones. The profiles were dissimilar from other known propolis types. They demonstrate that although Oman is not a large country, the plant sources of propolis vary significantly, even in the same apiary and the same season. Based on chemical profiles, and isolation and identification of major marker compounds (new propolis constituents), new plant sources of propolis were found: Azadiracta indica (neem tree) and Acacia spp. (most probably A. nilotica). The ethanol extracts of the studied propolis samples demonstrated activity against S. aureus (MIC < 100 μg. mL-1) and E. coli (MIC < 380 μg. mL-1). Conclusion Omani propolis is different form the known propolis types and demonstrates significant chemical diversity. Its most important plant source is the resin of Azadirachta indica, and as a result its typical components are С5-prenyl flavanones. Other plant sources have been identified, too, playing some role in resin collection by bees in Oman: Acacia spp. (most probably A. nilotica) and Mangifera indica. The results demonstrate also the potential of Omani propolis as antimicrobial. PMID:24053750

Classical and alternative activation of rat hepatic sinusoidal endothelial cells by inflammatory stimuli.

PubMed

Liu, Yinglin; Gardner, Carol R; Laskin, Jeffrey D; Laskin, Debra L

2013-02-01

The ability of rat hepatic sinusoidal endothelial cells (HSEC) to become activated in response to diverse inflammatory stimuli was analyzed. Whereas the classical macrophage activators, IFNγ and/or LPS upregulated expression of iNOS in HSEC, the alternative macrophage activators, IL-10 or IL-4+IL-13 upregulated arginase-1 and mannose receptor. Similar upregulation of iNOS and arginase-1 was observed in classically and alternatively activated Kupffer cells, respectively. Removal of inducing stimuli from the cells had no effect on expression of these markers, demonstrating that activation is persistent. Washing and incubation of IFNγ treated cells with IL-4+IL-13 resulted in decreased iNOS and increased arginase-1 expression, while washing and incubation of IL-4+IL-13 treated cells with IFNγ resulted in decreased arginase-1 and increased iNOS, indicating that classical and alternative activation of the cells is reversible. HSEC were more sensitive to phenotypic switching than Kupffer cells, suggesting greater functional plasticity. Hepatocyte viability and expression of PCNA, β-catenin and MMP-9 increased in the presence of alternatively activated HSEC. In contrast, the viability of hepatocytes pretreated for 2 h with 5 mM acetaminophen decreased in the presence of classically activated HSEC. These data demonstrate that activated HSEC can modulate hepatocyte responses following injury. The ability of hepatocytes to activate HSEC was also investigated. Co-culture of HSEC with acetaminophen-injured hepatocytes, but not control hepatocytes, increased the sensitivity of HSEC to classical and alternative activating stimuli. The capacity of HSEC to respond to phenotypic activators may represent an important mechanism by which they participate in inflammatory responses associated with hepatotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

SOME RESULTS FROM THE DEMONSTRATION OF INDOOR RADON REDUCTION MEASURES IN BLOCK BASEMENT HOUSES

EPA Science Inventory

Active soil ventilation techniques have been tested in 26 block-wall basement houses in eastern Pennsylvania with significantly elevated indoor radon concentrations, generally above 740 Bq/m3, and the results indicate that radon levels can be reduced substantially often below the...

Simultaneous Increases in Proliferation and Apoptosis of Vascular Smooth Muscle Cells Accelerate Diabetic Mouse Venous Atherosclerosis

PubMed Central

Liu, Shuying; Zhang, Zhengyu; Wang, Jingjing; Zhou, Yuhuan; Liu, Kefeng; Huang, Jintao; Chen, Dadi; Wang, Junmei; Li, Chaohong

2015-01-01

Aims This study was designed to demonstrate simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells (VSMCs) leading to accelerated vein graft remodeling and to explore the underlying mechanisms. Methods Vein grafts were performed in non-diabetic and diabetic mice. The cultured quiescent VSMCs were subjected to mechanical stretch stress (SS) and/or advanced glycosylation end products (AGEs). Harvested vein grafts and treated VSMCs were used to detect cell proliferation, apoptosis, mitogen-activated protein kinases (MAPKs) activation and SM-α-actin expression. Results Significantly thicker vessel walls and greater increases in proliferation and apoptosis were observed in diabetic vein grafts than those in non-diabetic. Both SS and AGEs were found to induce different activation of three members of MAPKs and simultaneous increases in proliferation and apoptosis of VSMCs, and combined treatment with both had a synergistic effect. VSMCs with strong SM-α-actin expression represented more activated JNKs or p38MAPK, and cell apoptosis, while the cells with weak SM-α-actin expression demonstrated preferential activation of ERKs and cell proliferation. In contrast, inhibition of MAPKs signals triggered significant decreases in VSMC proliferation, and apoptosis. Treatment of the cells with RNA interference of receptor of AGEs (RAGE) also resulted in significant decreases in both proliferation and apoptosis. Conclusions Increased pressure-induced SS triggers simultaneous increases in proliferation and apoptosis of VSMCs in the vein grafts leading to vein arterializations, which can be synergistically accelerated by high glucose-induced AGEs resulting in vein graft atherosclerosis. Either SS or AGEs and their combination induce simultaneous increases in proliferation and apoptosis of VSMCs via different activation of three members of MAPKs resulting from different VSMC subtypes classified by SM-α-actin expression levels. PMID:26488175

Activating catalysts with mechanical force.

PubMed

Piermattei, Alessio; Karthikeyan, S; Sijbesma, Rint P

2009-05-01

Homogeneously catalysed reactions can be 'switched on' by activating latent catalysts. Usually, activation is brought about by heat or an external chemical agent. However, activation of homogeneous catalysts with a mechanical trigger has not been demonstrated. Here, we introduce a general method to activate latent catalysts by mechanically breaking bonds between a metal and one of its ligands. We have found that silver(I) complexes of polymer-functionalized N-heterocyclic carbenes, which are latent organocatalysts, catalyse a transesterification reaction when exposed to ultrasound in solution. Furthermore, ultrasonic activation of a ruthenium biscarbene complex with appended polymer chains results in catalysis of olefin metathesis reactions. In each case, the catalytic activity results from ligand dissociation, brought about by transfer of mechanical forces from the polymeric substituents to the coordination bond. Mechanochemical catalyst activation has potential applications in transduction and amplification of mechanical signals, and mechanically initiated polymerizations hold promise as a novel repair mechanism in self-healing materials.

Investigation of photodynamic activity of water-soluble porphyrins in vitro and in vivo

NASA Astrophysics Data System (ADS)

Gyulkhandanyan, Grigor V.; Ghambaryan, Sona S.; Amelyan, Gayane V.; Ghazaryan, Robert K.; Arsenyan, Flora H.; Gyulkhandanyan, Aram G.

2006-02-01

Photodynamic therapy (PDT) is the method of photosensitized tumor treatment. It is based on the photosensitizer (PS) selective accumulation in tumors, its subsequent activation under the light influence and oxygen active form formation that results in tumor destruction. Photodynamic action of some new water-soluble porphyrins was investigated in our laboratory. Dose-dependent effect of these porphyrins was shown on PC-12 murine pheochromocytoma cell line. The results revealed that the efficiency of the investigated porphyrins decreased in the following way: TOEPyP (meso-tetra-(4-N-oxyethylpyridyl)porphyrin) > Zn-TOEPyP > Ag-TOEPyP. It was shown that TOEPyP possessed nearly the same photodynamic activity (LD50) as well-known photosensitizer chlorin e6. These porphyrins have also demonstrated quite high photodynamic activity in vivo. The results were obtained in the experiments on white mice with engrafted C-180 (Croker's sarcoma). Antitumor activity of these porphyrins in the dark was 30-40%, whereas photodynamic activity was 45-60%.

Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

PubMed Central

Hancock, Melissa L.; Canetta, Sarah E.; Role, Lorna W.; Talmage, David A.

2008-01-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function. PMID:18458158

Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.

PubMed

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-05-05

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons.

PubMed

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-06-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

NASA Astrophysics Data System (ADS)

D'Aquino, J. Alejandro; Ringe, Dagmar

2006-08-01

The diphtheria toxin repressor, DtxR, is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear (1 - 3). Calorimetric techniques have demonstrated that while binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 × 10-7, binding site 2 (primary) is a low affinity binding site with a binding constant of 6.3 × 10-4. These two binding sites act independently and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A,C102D), reported here and the previously reported DtxR(H79A) (4) has allowed us to propose a mechanism of metal ion activation for DtxR.

Waste inspection tomography (WIT)

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

Bernardi, R.T.

1996-12-31

WIT is a self-sufficient mobile semitrailer for nondestructive evaluation and nondestructive assay of nuclear waste drums using x-ray and gamma-ray tomography. The recently completed Phase I included the design, fabrication, and initial testing of all WIT subsystems installed on-board the trailer. Initial test results include 2 MeV digital radiography, computed tomography, Anger camera imaging, single photon emission computed tomography, gamma-ray spectroscopy, collimated gamma scanning, and active and passive computed tomography using a 1.4 mCi source of {sup 166}Ho. These techniques were initially demonstrated on a 55-gallon phantom drum with 3 simulated waste matrices of combustibles, heterogeneous metals, and cement usingmore » check sources of gamma active isotopes such as {sup 137}Cs and {sup 133}Ba with 9-250 {mu}Ci activities. Waste matrix identification, isotopic identification, and attenuation-corrected gamma activity determination were demonstrated nondestructively and noninvasively in Phase I. Currently ongoing Phase II involves DOE site field test demonstrations at LLNL, RFETS, and INEL with real nuclear waste drums. Current WIT experience includes 55 gallon drums of cement, graphite, sludge, glass, metals, and combustibles. Thus far WIT has inspected drums with 0-20 gms of {sup 239}Pu.« less

Breast Milk of HIV-Positive Mothers Has Potent and Species-Specific In Vivo HIV-Inhibitory Activity

PubMed Central

Wahl, Angela; Baker, Caroline; Spagnuolo, Rae Ann; Stamper, Lisa W.; Fouda, Genevieve G.; Permar, Sallie R.; Hinde, Katie; Kuhn, Louise; Bode, Lars; Aldrovandi, Grace M.

2015-01-01

ABSTRACT Despite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed to anti-HIV factors in breast milk. Breast milk of HIV-negative women can inhibit HIV infection. However, the HIV-inhibitory activity of breast milk from HIV-positive mothers has not been evaluated. In addition, while significant differences in breast milk composition between transmitting and nontransmitting HIV-positive mothers have been correlated with transmission risk, the HIV-inhibitory activity of their breast milk has not been compared. This knowledge may significantly impact the design of prevention approaches in resource-limited settings that do not deny infants of HIV-positive women the health benefits of breast milk. Here, we utilized bone marrow/liver/thymus humanized mice to evaluate the in vivo HIV-inhibitory activity of breast milk obtained from HIV-positive transmitting and nontransmitting mothers. We also assessed the species specificity and biochemical characteristics of milk's in vivo HIV-inhibitory activity and its ability to inhibit other modes of HIV infection. Our results demonstrate that breast milk of HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast milk can prevent multiple routes of infection. Most importantly, this activity is unique to human milk. Our results also suggest multiple factors in breast milk may contribute to its HIV-inhibitory activity. Collectively, our results support current recommendations that HIV-positive mothers in resource-limited settings exclusively breastfeed in combination with antiretroviral therapy. IMPORTANCE Approximately 240,000 children become infected with HIV annually, the majority via breastfeeding. Despite daily exposure to virus in breast milk, most infants breastfed by HIV-positive women do not acquire HIV. The low risk of breastfeeding-associated HIV transmission is likely due to antiviral factors in breast milk. It is well documented that breast milk of HIV-negative women can inhibit HIV infection. Here, we demonstrate, for the first time, that breast milk of HIV-positive mothers (nontransmitters and transmitters) inhibits HIV transmission. We also demonstrate that breast milk can prevent multiple routes of HIV acquisition and that this activity is unique to human milk. Collectively, our results support current guidelines which recommend that HIV-positive women in resource-limited settings exclusively breastfeed in combination with infant or maternal antiretroviral therapy. PMID:26292320

Activation of Stat3 Transcription Factor by Herpesvirus Saimiri STP-A Oncoprotein

PubMed Central

Chung, Young-Hwa; Cho, Nam-hyuk; Garcia, Maria Ines; Lee, Sun-Hwa; Feng, Pinghui; Jung, Jae U.

2004-01-01

The saimiri transforming protein (STP) oncogene of Herpesvirus saimiri subgroup A strain 11 (STP-A11) is not required for viral replication but is required for lymphoid cell immortalization in culture and lymphoma induction in primates. We previously showed that STP-A11 interacts with cellular Src kinase through its SH2 binding motif and that this interaction elicits Src signal transduction. Here we demonstrate that STP-A11 interacts with signal transducer and activator of transcription 3 (Stat3) independently of Src association and that the amino-terminal short proline-rich motif of STP-A11 and the central linker region of Stat3 are necessary for their interaction. STP-A11 formed a triple complex with Src kinase and Stat3 where Src kinase phosphorylated Stat3, resulting in the nuclear localization and transcriptional activation of Stat3. Consequently, the constitutively active Stat3 induced by STP-A11 elicited cellular signal transduction, which ultimately induced cell survival and proliferation upon serum deprivation. Furthermore, this activity was strongly correlated with the induction of Fos, cyclin D1, and Bcl-XL expression. These results demonstrate that STP-A11 independently targets two important cellular signaling molecules, Src and Stat3, and that these proteins cooperate efficiently to induce STP-A11-mediated transformation. PMID:15163742

Flagellar motility is a key determinant of the magnitude of the inflammasome response to Pseudomonas aeruginosa.

PubMed

Patankar, Yash R; Lovewell, Rustin R; Poynter, Matthew E; Jyot, Jeevan; Kazmierczak, Barbara I; Berwin, Brent

2013-06-01

We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report that inflammasome activation is reduced in response to nonmotile P. aeruginosa. Nonmotile P. aeruginosa elicits reduced IL-1β production as well as caspase-1 activation by peritoneal macrophages and bone marrow-derived dendritic cells in vitro. Importantly, nonmotile P. aeruginosa also elicits reduced IL-1β levels in vivo in comparison to those elicited by wild-type P. aeruginosa. This is the first demonstration that loss of bacterial motility results in reduced inflammasome activation and antibacterial IL-1β host response. These results provide a critical insight into how the innate immune system responds to bacterial motility and, correspondingly, how pathogens have evolved mechanisms to evade the innate immune system.

Flagellar Motility Is a Key Determinant of the Magnitude of the Inflammasome Response to Pseudomonas aeruginosa

PubMed Central

Patankar, Yash R.; Lovewell, Rustin R.; Poynter, Matthew E.; Jyot, Jeevan; Kazmierczak, Barbara I.

2013-01-01

We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report that inflammasome activation is reduced in response to nonmotile P. aeruginosa. Nonmotile P. aeruginosa elicits reduced IL-1β production as well as caspase-1 activation by peritoneal macrophages and bone marrow-derived dendritic cells in vitro. Importantly, nonmotile P. aeruginosa also elicits reduced IL-1β levels in vivo in comparison to those elicited by wild-type P. aeruginosa. This is the first demonstration that loss of bacterial motility results in reduced inflammasome activation and antibacterial IL-1β host response. These results provide a critical insight into how the innate immune system responds to bacterial motility and, correspondingly, how pathogens have evolved mechanisms to evade the innate immune system. PMID:23529619

Bioassays and field immersion tests: a comparison of the antifouling activity of copper-free poly(methacrylic)-based coatings containing tertiary amines and ammonium salt groups.

PubMed

Bressy, C; Hellio, C; Marechal, J P; Tanguy, B; Margaillan, A

2010-10-01

This paper focuses on the activity spectrum of three dimethylalkyl tertiary amines as potential active molecules and the corresponding ammonium salt-based antifouling (AF) paints. Bioassays (using marine bacteria, microalgae and barnacles) and field tests were combined to assess the AF activity of coatings. Bioassay results demonstrated that the ammonium salt-based paints did not inhibit the growth of microorganisms (except the dimethyldodecylammonium-based coatings) and that the tertiary amines were potent towards bacteria, diatoms, and barnacle larvae at non-toxic concentrations (therapeutic ratio, LC50/EC50, <1). The results from field tests indicated that the ammonium salt-based coatings inhibited the settlement of macrofouling and the dimethylhexadecylammonium-based coatings provided protection against slime in comparison with PVC blank panels. Thus, results from laboratory assays did not fully concur with the AF activity of the paints in the field trial.

Bottom-up driven involuntary auditory evoked field change: constant sound sequencing amplifies but does not sharpen neural activity.

PubMed

Okamoto, Hidehiko; Stracke, Henning; Lagemann, Lothar; Pantev, Christo

2010-01-01

The capability of involuntarily tracking certain sound signals during the simultaneous presence of noise is essential in human daily life. Previous studies have demonstrated that top-down auditory focused attention can enhance excitatory and inhibitory neural activity, resulting in sharpening of frequency tuning of auditory neurons. In the present study, we investigated bottom-up driven involuntary neural processing of sound signals in noisy environments by means of magnetoencephalography. We contrasted two sound signal sequencing conditions: "constant sequencing" versus "random sequencing." Based on a pool of 16 different frequencies, either identical (constant sequencing) or pseudorandomly chosen (random sequencing) test frequencies were presented blockwise together with band-eliminated noises to nonattending subjects. The results demonstrated that the auditory evoked fields elicited in the constant sequencing condition were significantly enhanced compared with the random sequencing condition. However, the enhancement was not significantly different between different band-eliminated noise conditions. Thus the present study confirms that by constant sound signal sequencing under nonattentive listening the neural activity in human auditory cortex can be enhanced, but not sharpened. Our results indicate that bottom-up driven involuntary neural processing may mainly amplify excitatory neural networks, but may not effectively enhance inhibitory neural circuits.

Short-term and long-term effects of protein kinase C on the trafficking and stability of human organic anion transporter 3

PubMed Central

Zhang, Qiang; Suh, Wonmo; Pan, Zui; You, Guofeng

2012-01-01

Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that short-term activation of PKC by phobol 12-Myristate 13-Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by immunolocalization with confocal microscopy. Furthermore, we showed that long-term activation of PKC resulted in the enhanced degradation of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate that PKC plays critical roles in the trafficking and the stability of hOAT3. PMID:22773962

Study on adsorption properties and mechanism of Pb2+ with different carbon based adsorbents.

PubMed

Song, Min; Wei, Yuexing; Cai, Shipan; Yu, Lei; Zhong, Zhaoping; Jin, Baosheng

2018-03-15

Different activated carbon materials are prepared from a series of solid wastes (sawdust, acrylic fabric, tire powder and rice husk) by combination of the KOH activation method and steam activation method. The influences of several parameters such as pH, contact time, adsorbent dosage and temperature on adsorption performance of Pb 2+ with those different carbon adsorbents are investigated. The results demonstrate that C rice husk performance well in the adsorption process. In the following, the C rice husk is used to explain the adsorption mechanism of Pb 2+ by SEM-EDS, FT-IR and XPS. The results illustrate that the surface oxygen-containing functional groups such as carboxyl, lactone group, phenolic hydroxyl and other alkaline metal ions like Na + and K + have significant effect on the adsorption process. A reasonable mechanism of Pb 2+ adsorption is proposed that the ion exchange play key roles in the adsorption process. In addition, the effects of Cu 2+ , Zn 2+ on the Pb 2+ adsorption capacity with the four carbon adsorbents are also studied and the results demonstrate that other heavy metals play positive effects on the adsorption of Pb 2+ . Copyright © 2017 Elsevier B.V. All rights reserved.

Free Radical Scavenging Activity of Scoparia dulcis Extract.

PubMed

Babincová, M.; Sourivong, P.

2001-01-01

We studied the scavenging capabilities of an extract of Scoparia dulcis (a cosmopolitan weed widespread in Laos and Vietnam) for 1-diphenyl-2-picrylhydrazyl and measured hemoglobin-catalyzed linoleic acid peroxidation with an oxygen electrode. Our results demonstrated strong antioxidant activity corresponding to mitigation of the generation of hydroxyl radicals, a possible rationale for the observed therapeutic effects of this weed.

PE in Pictures: Using Photovoice to Promote Middle School Students' Reflections on Physical Activity during Free Time

ERIC Educational Resources Information Center

Treadwell, Sheri M.; Taylor, Neva

2017-01-01

The purpose of this article is to demonstrate how physical educators can use Photovoice to examine their students' perceptions of physical activity and healthy living, and ultimately advocate for change in both their school and community. As a result of student participation in a physical education class project that utilized Photovoice,…

Liposomes as protective capsules for active silica sol-gel biocomposite synthesis.

PubMed

Li, Ye; Yip, Wai Tak

2005-09-21

Using liposome to shield an enzyme from hostile chemical environments during the sol-gel formation process has resulted in a novel approach to synthesizing silica sol-gel biocomposite materials. By reporting the encapsulation of horseradish peroxidase and firefly luciferase, we demonstrate that this new protocol can produce silica biocomposites that are more active than trapping the enzymes directly into hydrogels.

Microbial Survey of a Full-Scale, Biologically Active Filter for Treatment of Drinking Water

PubMed Central

DeBry, Ronald W.; Lytle, Darren A.

2012-01-01

The microbial community of a full-scale, biologically active drinking water filter was surveyed using molecular techniques. Nitrosomonas, Nitrospira, Sphingomonadales, and Rhizobiales dominated the clone libraries. The results elucidate the microbial ecology of biological filters and demonstrate that biological treatment of drinking water should be considered a viable alternative to physicochemical methods. PMID:22752177

Importance of Residue 13 and the C-Terminus for the Structure and Activity of the Antimicrobial Peptide Aurein 2.2

PubMed Central

Cheng, John T.J.; Hale, John D.; Kindrachuk, Jason; Jessen, Havard; Elliott, Melissa; Hancock, Robert E.W.; Straus, Suzana K.

2010-01-01

Previous studies on aurein 2.2 and 2.3 in DMPC/DMPG and POPC/POPG membranes have shown that bilayer thickness and phosphatidylglycerol content have a significant impact on the interaction of these peptides with membrane bilayers. Further examination with the DiSC35 assay has indicated that aurein 2.2 induces greater membrane leakage than aurein 2.3 in Staphylococcus aureus C622. The only difference between these peptides is a Leu to Ile mutation at residue 13. To better understand the importance of this residue, the structure and activity of the L13A, L13F, and L13V mutants were investigated. In addition, we investigated a number of peptides with truncations at the C-terminus to determine whether the C-terminus, which contains residue 13, is crucial for antimicrobial activity. Solution circular dichroism results demonstrated that the L13F mutation and the truncation of the C-terminus by six residues resulted in decreased helical content, whereas the L13A or L13V mutation and the truncation of the C-terminus by three residues showed little to no effect on the structure. Oriented circular dichroism results demonstrated that only an extensive C-terminal truncation reduced the ability of the peptide to insert into lipid bilayers. 31P NMR spectroscopy showed that all peptides disorder the headgroups. The implications of these results in terms of antimicrobial activity and the ability of these peptides to induce leakage in S. aureus are discussed. The results suggest that the presence of the 13th residue in aurein 2.2 is important for structure and activity, but the exact nature of residue 13 is less important as long as it is a hydrophobic residue. PMID:21044590

The role of Patient Health Engagement Model (PHE-model) in affecting patient activation and medication adherence: A structural equation model

PubMed Central

Graffigna, Guendalina; Bonanomi, Andrea

2017-01-01

Background Increasing bodies of scientific research today examines the factors and interventions affecting patients’ ability to self-manage and adhere to treatment. Patient activation is considered the most reliable indicator of patients’ ability to manage health autonomously. Only a few studies have tried to assess the role of psychosocial factors in promoting patient activation. A more systematic modeling of the psychosocial factors explaining the variance of patient activation is needed. Objective To test the hypothesized effect of patient activation on medication adherence; to test the the hypothesized effects of positive emotions and of the quality of the patient/doctor relationship on patient activation; and to test the hypothesized mediating effect of Patient Health Engagement (PHE-model) in this pathway. Material and methods This cross-sectional study involved 352 Italian-speaking adult chronic patients. The survey included measures of i) patient activation (Patient Activation Measure 13 –short form); ii) Patient Health Engagement model (Patient Health Engagement Scale); iii) patient adherence (4 item-Morinsky Medication Adherence Scale); iv) the quality of the patients’ emotional feelings (Manikin Self Assessment Scale); v) the quality of the patient/doctor relationship (Health Care Climate Questionnaire). Structural equation modeling was used to test the hypotheses proposed. Results According to the theoretical model we hypothesized, research results confirmed that patients’ activation significantly affects their reported medication adherence. Moreover, psychosocial factors, such as the patients’ quality of the emotional feelings and the quality of the patient/doctor relationship were demonstrated to be factors affecting the level of patient activation. Finally, the mediation effect of the Patient Health Engagement model was confirmed by the analysis. Conclusions Consistently with the results of previous studies, these findings demonstrate that the Patient Health Engagement Model is a critical factor in enhancing the quality of care. The Patient Health Engagement Model might acts as a mechanism to increase patient activation and adherence. PMID:28654686

Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species.

PubMed

Zhang, Aifeng; Sheng, Yuqing; Zou, Mingchang

2017-03-01

Previous studies have demonstrated that Alisol B has inhibitory activity in cancer cells. However, the exact mechanism through which inhibition is achieved is still poorly understood. In the present study, the authors examined the effects of Alisol B in human breast cancer cells. Alisol B showed significant anticancer activity in MDA-MB-231 cells. The results demonstrated that the cytotoxicity induced by Alisol B was mediated by induction of apoptosis, decrease in mitochondrial membrane potential, cell cycle arrest, activation of caspases and accumulation of ROS (reactive oxygen species) level. Interestingly, pretreatment of cells with the general caspase inhibitor z-VAD-FMK significantly prevented Alisol B-induced apoptosis. Furthermore, western blot analysis revealed the upregulation of p-p38 and downregulation of p-AKT, p-p65 and p-mTOR. Taken together, the above results suggest that Alisol B suppresses the growth of MDA-MB-231 cells mainly through induction of apoptosis; this outcome may represent the major mechanism of Alisol B-mediated apoptosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effects of poly (lactic-co-glycolic acid) as a co-emulsifier on the preparation and hypoglycaemic activity of insulin-loaded solid lipid nanoparticles.

PubMed

Wang, S L; Xie, S Y; Zhu, L Y; Wang, F H; Zhou, W Z

2009-12-01

Poly (lactic-co-glycolic acid) (PLGA) was used as a co-emulsifier in the preparation of insulin-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil as lipid matrix and lecithin as surfactant by double-emulsion technique. The effects of PLGA on the preparation and hypoglycaemic activity of insulin-loaded SLN were studied. The results showed that with the supplement of PLGA, the encapsulation efficiency and loading capacity were increased significantly from 79.08 +/- 1.62 to 85.57 +/- 3.21% and 1.58 +/- 0.03 to 1.71 +/- 0.06%, whereas the surface charge and particle size were changed insignificantly from -25.87 +/- 2.65 to -22.67 +/- 1.19 mv and 431.0 +/- 16.1 to 397.0 +/- 68.0 nm, respectively. In vivo studies demonstrated that PLGA increased the sustained hypoglycaemic activity from 12 to 36 h and 24 to 120 h in normal and steptozotocin-induced diabetic mice after a single intramuscular injection of the insulin-loaded SLN. These results demonstrated that PLGA could enhance the entrapment of insulin in the nanoparticles, and more importantly, prolong the time of hypoglycaemic activity of the insulin-loaded SLN.

The associations among fundamental movement skills, self-reported physical activity and academic performance during junior high school in Finland.

PubMed

Jaakkola, Timo; Hillman, Charles; Kalaja, Sami; Liukkonen, Jarmo

2015-01-01

The purpose of this study was to analyse the longitudinal associations between (1) fundamental movement skills (FMSs) and academic performance, and (2) self-reported physical activity and academic performance through junior high school in Finland. The participants of the study were 325 Finnish students (162 girls and 163 boys), who were 13 years old at the beginning of the study at Grade 7. Students performed three FMS tests and responded to a self-reported physical activity questionnaire at Grades 7 and 8. Marks in Finnish language, mathematics and history from Grades 7, 8 and 9 were collected. Structural equation modelling with multigroup method demonstrated that in the boys' group, a correlation (0.17) appeared between FMS and academic performance measured at Grade 7. The results also indicated that FMS collected at Grade 8 were significantly but weakly (path coefficient 0.14) associated with academic performance at Grade 9 for both gender groups. Finally, the results of this study demonstrated that self-reported physical activity was not significantly related to academic performance during junior high school. The findings of this study suggest that mastery of FMS may contribute to better student achievement during junior high school.

Antiretroviral therapy in HIV-1-infected individuals with CD4 count below 100 cells/mm3 results in differential recovery of monocyte activation

PubMed Central

Patro, Sean C.; Azzoni, Livio; Joseph, Jocelin; Fair, Matthew G.; Sierra-Madero, Juan G.; Rassool, Mohammed S.; Sanne, Ian; Montaner, Luis J.

2016-01-01

Reversal of monocyte and macrophage activation and the relationship to viral suppression and T cell activation are unknown in patients with advanced HIV-1 infection, initiating antiretroviral therapy. This study aimed to determine whether reduction in biomarkers of monocyte and macrophage activation would be reduced in conjunction with viral suppression and resolution of T cell activation. Furthermore, we hypothesized that the addition of CCR5 antagonism (by maraviroc) would mediate greater reduction of monocyte/macrophage activation markers than suppressive antiretroviral therapy alone. In the CCR5 antagonism to decrease the incidence of immune reconstitution inflammatory syndrome study, antiretroviral therapy-naïve patients received maraviroc or placebo in addition to standard antiretroviral therapy. PBMCs and plasma from 65 patients were assessed during 24 wk of antiretroviral therapy for biomarkers of monocyte and macrophage activation. Markers of monocyte and macrophage activation were reduced significantly by 24 wk, including CD14++CD16+ intermediate monocytes (P < 0.0001), surface CD163 (P = 0.0004), CD169 (P < 0.0001), tetherin (P = 0.0153), and soluble CD163 (P < 0.0001). A change in CD38+, HLA-DR+ CD8 T cells was associated with changes in CD169 and tetherin expression. Maraviroc did not affect biomarkers of monocyte/macrophage activation but resulted in greater percentages of CCR5-positive monocytes in PBMC. HIV-1 suppression after 24 wk of antiretroviral therapy, with or without maraviroc, demonstrates robust recovery in monocyte subset activation markers, whereas soluble markers of activation demonstrate minimal decrease, qualitatively differentiating markers of monocyte/macrophage activation in advanced disease. PMID:26609048

Identification and characterization of a receptor for tissue ferritin on activated rat lipocytes.

PubMed Central

Ramm, G A; Britton, R S; O'Neill, R; Bacon, B R

1994-01-01

Hepatic iron overload causes lipocyte activation with resultant fibrogenesis. This study examines whether rat lipocytes express ferritin receptors, which could be involved in paracellular iron movement and in cellular regulation. Lipocytes from normal rat liver were cultured on plastic and incubated with 125I-labeled rat liver ferritin (RLF) +/- a 100-fold excess of either unlabeled RLF or human heart ferritin, human liver ferritin, human recombinant H-ferritin, a mutant human recombinant L-ferritin, or a variety of nonspecific proteins. Specific binding sites for ferritin were demonstrated by displacement of 125I-RLF by RLF (64.5 +/- 4.3%) and by other ferritins (55-60%), but not by recombinant L-ferritin. Scatchard analysis demonstrated a single class of binding sites with a Kd of 5.1 +/- 2.9 x 10(-10) M, maximum binding capacity of 4.7 +/- 1.3 x 10(-12) M, and 5,000-10,000 receptor sites/cell. Ferritin receptor expression was observed only in activated lipocytes. Internalization of RLF was observed within 15 min using FITC-RLF and confocal microscopy. This study demonstrates that (a) activated lipocytes express a specific high affinity ferritin receptor; (b) the binding appears to be dependent on the H-ferritin subunit; and (c) lipocytes internalize ferritin. Expression of ferritin receptors in activated lipocytes suggests that the receptor may either be involved in the activation cascade or may be a marker of activation. Images PMID:8040296

Demonstration of brain noise on human EEG signals in perception of bistable images

NASA Astrophysics Data System (ADS)

Grubov, Vadim V.; Runnova, Anastasiya E.; Kurovskaya, Maria K.; Pavlov, Alexey N.; Koronovskii, Alexey A.; Hramov, Alexander E.

2016-03-01

In this report we studied human brain activity in the case of bistable visual perception. We proposed a new approach for quantitative characterization of this activity based on analysis of EEG oscillatory patterns and evoked potentials. Accordingly to theoretical background, obtained experimental EEG data and results of its analysis we studied a characteristics of brain activity during decision-making. Also we have shown that decisionmaking process has the special patterns on the EEG data.

MicroRNAs, polyamines, and the activities antioxidant enzymes are associated with in vitro rooting in white pine (Pinus strobus L.).

PubMed

Fei, Yunjun; Xiao, Bo; Yang, Man; Ding, Qiong; Tang, Wei

2016-01-01

Molecular mechanism of in vitro rooting in conifer is not fully understood. After establishment of a regeneration procedure in eastern white pine (Pinus strobus L.) using mature embryos as explants to induce shoot formation on medium containing 3 μM IAA, 6 μM BA and 6 μM TDZ and induce root formation on medium containing 0.001-0.05 μM IAA, 0.001-0.05 μM IBA, 0.001-0.05 μM TDZ, we have investigated the changes of polyamine content and the activities of antioxidant enzymes during in vitro rooting in P. strobus. Our results demonstrated that putrescine (Put), spermidine (Spd), and spermine (Spm) did not increase in P. strobus during the first week of rooting on medium supplemented with 0.01 μM indole-3-acetic acid (IAA), whereas the levels of Put, Spd, and Spm increased during the 1st-3rd week of culture on medium with IAA, and then decreased on medium with IAA. No such a change in Put, Spd, and Spm was observed on medium without IAA. Measurement of antioxidant enzyme activity demonstrated that the activities of polyphenol oxidase, catalase, and peroxidase slightly increased in the first week of culture and reached to the highest peak in the 3rd-5th week of culture. Quantitative RT-PCR results indicated that miR160 was increased on the 7th day, miR162, miR397, and miR408 was increased from the 21th to 35th day, miR857 was increased on the 35th day, and miR827 was increased on the 49th day. These results demonstrated that enhanced polyamine biosynthesis, antioxidant enzyme activity, and microRNAs are correlated with the root induction and formation in P. strobus.

Design of Embedded-Hybrid Antimicrobial Peptides with Enhanced Cell Selectivity and Anti-Biofilm Activity

PubMed Central

Xu, Wei; Zhu, Xin; Tan, Tingting; Li, Weizhong; Shan, Anshan

2014-01-01

Antimicrobial peptides have attracted considerable attention because of their broad-spectrum antimicrobial activity and their low prognostic to induce antibiotic resistance which is the most common source of failure in bacterial infection treatment along with biofilms. The method to design hybrid peptide integrating different functional domains of peptides has many advantages. In this study, we designed an embedded-hybrid peptide R-FV-I16 by replacing a functional defective sequence RR7 with the anti-biofilm sequence FV7 embedded in the middle position of peptide RI16. The results demonstrated that the synthetic hybrid the peptide R-FV-I16 had potent antimicrobial activity over a wide range of Gram-negative and Gram-positive bacteria, as well as anti-biofilm activity. More importantly, R-FV-I16 showed lower hemolytic activity and cytotoxicity. Fluorescent assays demonstrated that R-FV-I16 depolarized the outer and the inner bacterial membranes, while scanning electron microscopy and transmission electron microscopy further indicated that this peptide killed bacterial cells by disrupting the cell membrane, thereby damaging membrane integrity. Results from SEM also provided evidence that R-FV-I16 inherited anti-biofilm activity from the functional peptide sequence FV7. Embedded-hybrid peptides could provide a new pattern for combining different functional domains and showing an effective avenue to screen for novel antimicrobial agents. PMID:24945359

Geographic Origin and Host Cultivar Influence on Digestive Physiology of Spodoptera exigua (Lepidoptera: Noctuidae) Larvae

PubMed Central

Golikhajeh, Neshat; Razmjou, Jabraeil

2017-01-01

Digestive enzymatic activity in three geographic strains (Miandiab, Kalposh and Moghan regions) of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) reared on different sugar beet cultivars (Dorothea, Rozier, Persia and Perimer) was studied under laboratory conditions (25 ± 1 °C, 65 ± 5% RH, and a photo period of 16:8 (L:D) h photoperiod). The results of this study demonstrated that digestive protease and amylase activity of S. exigua larvae was affected by both geographic origin of the pest and host plant cultivar. Three strains reared on the same sugar beet cultivars demonstrated different levels of proteolytic and amylolytic activities in fourth and fifth instars. The highest proteolytic and amylolytic activity, in most cases, was observed in larvae collected from Kalposh region. Among different sugar beet cultivars, the highest protease activity in three strains was observed on cultivars Rozier and Perimer. Nevertheless, the highest amylase activity was seen on cultivar Dorothea, and the lowest activity was seen on cultivar Rozier. This study suggested that variations in digestive enzymatic activity of three geographic strains of S. exigua might be attributed to local adaptation with their local host plant and environmental conditions inherent by larvae. PMID:28069730

Tissue plasminogen activator mediates amyloid-induced neurotoxicity via Erk1/2 activation

PubMed Central

Medina, Manel G; Ledesma, Maria Dolores; Domínguez, Jorge E; Medina, Miguel; Zafra, Delia; Alameda, Francesc; Dotti, Carlos G; Navarro, Pilar

2005-01-01

Tissue plasminogen activator (tPA) is the main activator of plasminogen into plasmin in the brain where it may have beneficial roles but also neurotoxic effects that could be plasmin dependent or not. Little is known about the substrates and pathways that mediate plasmin-independent tPA neurotoxicity. Here we show in primary hippocampal neurons that tPA promotes a catalytic-independent activation of the extracellular regulated kinase (Erk)1/2 signal transduction pathway through the N-methyl-D-aspartate receptor, G-proteins and protein kinase C. This results in GSK3 activation in a process that requires de novo synthesis of proteins, and leads to tau aberrant phosphorylation, microtubule destabilization and apoptosis. Similar effects are produced by amyloid aggregates in a tPA-dependent manner, as demonstrated by pharmacological treatments and in wt and tPA−/− mice neurons. Consistently, in Alzheimer's disease (AD) patients' brains, high levels of tPA colocalize with amyloid-rich areas, activated Erk1/2 and phosphorylated tau. This is the first demonstration of an intracellular pathway by which tPA triggers kinase activation, tau phosphorylation and neurotoxicity, suggesting a key role for this molecule in AD pathology. PMID:15861134

Genetically determined interaction between the dopamine transporter and the D2 receptor on prefronto-striatal activity and volume in humans.

PubMed

Bertolino, Alessandro; Fazio, Leonardo; Di Giorgio, Annabella; Blasi, Giuseppe; Romano, Raffaella; Taurisano, Paolo; Caforio, Grazia; Sinibaldi, Lorenzo; Ursini, Gianluca; Popolizio, Teresa; Tirotta, Emanuele; Papp, Audrey; Dallapiccola, Bruno; Borrelli, Emiliana; Sadee, Wolfgang

2009-01-28

Dopamine modulation of neuronal activity during memory tasks identifies a nonlinear inverted-U shaped function. Both the dopamine transporter (DAT) and dopamine D(2) receptors (encoded by DRD(2)) critically regulate dopamine signaling in the striatum and in prefrontal cortex during memory. Moreover, in vitro studies have demonstrated that DAT and D(2) proteins reciprocally regulate each other presynaptically. Therefore, we have evaluated the genetic interaction between a DRD(2) polymorphism (rs1076560) causing reduced presynaptic D(2) receptor expression and the DAT 3'-VNTR variant (affecting DAT expression) in a large sample of healthy subjects undergoing blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging (MRI) during memory tasks and structural MRI. Results indicated a significant DRD(2)/DAT interaction in prefrontal cortex and striatum BOLD activity during both working memory and encoding of recognition memory. The differential effect on BOLD activity of the DAT variant was mostly manifest in the context of the DRD(2) allele associated with lower presynaptic expression. Similar results were also evident for gray matter volume in caudate. These interactions describe a nonlinear relationship between compound genotypes and brain activity or gray matter volume. Complementary data from striatal protein extracts from wild-type and D(2) knock-out animals (D2R(-/-)) indicate that DAT and D(2) proteins interact in vivo. Together, our results demonstrate that the interaction between genetic variants in DRD(2) and DAT critically modulates the nonlinear relationship between dopamine and neuronal activity during memory processing.

Anticipatory activity in the human thalamus is predictive of reaction times.

PubMed

Nikulin, V V; Marzinzik, F; Wahl, M; Schneider, G-H; Kupsch, A; Curio, G; Klostermann, F

2008-09-09

Responding to environmental stimuli in a fast manner is a fundamental behavioral capacity. The pace at which one responds is known to be predetermined by cortical areas, but it remains to be shown if subcortical structures also take part in defining motor swiftness. As the thalamus has previously been implicated in behavioral control, we tested if neuronal activity at this level could also predict the reaction time of upcoming movements. To this end we simultaneously recorded electrical brain activity from the scalp and the ventral intermediate nucleus (VIM) of the thalamus in patients undergoing thalamic deep brain stimulation. Based on trial-to-trial analysis of a Go/NoGo task, we demonstrate that both cortical and thalamic neuronal activity prior to the delivery of upcoming Go stimulus correlates with the reaction time. This result goes beyond the demonstration of thalamic activity being associated with but potentially staying invariant to motor performance. In contrast, it indicates that the latencies at which we respond to environmental stimuli are not exclusively related to cortical pre-movement states but are also correlated with anticipatory thalamic activity.

Effect of lactobacillus strains on phenolic profile, color attributes and antioxidant activities of lactic-acid-fermented mulberry juice.

PubMed

Kwaw, Emmanuel; Ma, Yongkun; Tchabo, William; Apaliya, Maurice Tibiru; Wu, Meng; Sackey, Augustina Sackle; Xiao, Lulu; Tahir, Haroon Elrasheid

2018-06-01

This study was conducted to investigate the effect of lactic acid bacteria (LAB) strains on color properties, phenolic profile and antioxidant activities of mulberry juice. Mulberry juice was separately fermented at 37 °C for 36 h using Lactobacillus plantarum, Lactobacillus acidophilus and Lactobacillus paracasei. The results showed that lactic acid fermentation impacted on the color of the juice. Moreover, the study demonstrated that LABs impacted on the phenolic profile of the juice. Syringic acid, cyanidin-3-O-rutinoside and quercetin were the predominant phenolic acid, anthocyanin and flavonol respectively in the lactic-acid-fermented mulberry juice. The degree of radical scavenging activity was species-specific with the L. plantarum fermented juice having the highest radical scavenging activities. The correlation analysis demonstrated that flavonols and anthocyanins were mostly responsible for the increased in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity while phenolic acids and flavonols were responsible for 2,2-diphenyl-1-picrylhydrazyl scavenging activity and reducing power capacity of the fermented juice. Copyright © 2018 Elsevier Ltd. All rights reserved.

Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

PubMed Central

Oláh, Julianna; Mulholland, Adrian J.; Harvey, Jeremy N.

2011-01-01

Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are compared using molecular dynamics (MD) simulations and density functional theory (DFT). The DFT results on a small active site model suggest that both reactions might occur competitively. Docking and MD studies of dextromethorphan in the active site of P450 2D6 show that the dextromethorphan is located close to heme oxygen in a geometry apparently consistent with competitive metabolism. In contrast, calculations of the reaction path in a large protein model [using a hybrid quantum mechanical–molecular mechanics (QM/MM) method] show a very strong preference for O-demethylation, in accordance with experimental results. The aromatic carbon oxidation reaction is predicted to have a high activation energy, due to the active site preventing formation of a favorable transition-state structure. Hence, the QM/MM calculations demonstrate a crucial role of many active site residues in determining reactivity of dextromethorphan in P450 2D6. Beyond substrate binding orientation and reactivity of Compound I, successful metabolite predictions must take into account the detailed mechanism of oxidation in the protein. These results demonstrate the potential of QM/MM methods to investigate specificity in drug metabolism. PMID:21444768

In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma

PubMed Central

Fisher, T.; Golan, H.; Schiby, G.; PriChen, S.; Smoum, R.; Moshe, I.; Peshes-Yaloz, N.; Castiel, A.; Waldman, D.; Gallily, R.; Mechoulam, R.; Toren, A.

2016-01-01

Background Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects. Methods We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ9-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally determine the effects of those compounds on viability, invasiveness, cell cycle distribution, and programmed cell death in human nbl SK-N-SH cells. Results Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis (as demonstrated by morphology changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts. Conclusions Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl. PMID:27022310

Re-evaluating the efficacy of beta-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling.

PubMed

Ahrens-Nicklas, Rebecca C; Clancy, Colleen E; Christini, David J

2009-06-01

Long QT syndrome (LQTS) is a heterogeneous collection of inherited cardiac ion channelopathies characterized by a prolonged electrocardiogram QT interval and increased risk of sudden cardiac death. Beta-adrenergic blockers are the mainstay of treatment for LQTS. While their efficacy has been demonstrated in LQTS patients harbouring potassium channel mutations, studies of beta-blockers in subtype 3 (LQT3), which is caused by sodium channel mutations, have produced ambiguous results. In this modelling study, we explore the effects of beta-adrenergic drugs on the LQT3 phenotype. In order to investigate the effects of beta-adrenergic activity and to identify sources of ambiguity in earlier studies, we developed a computational model incorporating the effects of beta-agonists and beta-blockers into an LQT3 mutant guinea pig ventricular myocyte model. Beta-activation suppressed two arrhythmogenic phenomena, transmural dispersion of repolarization and early after depolarizations, in a dose-dependent manner. However, the ability of beta-activation to prevent cardiac conduction block was pacing-rate-dependent. Low-dose beta-blockade by propranolol reversed the beneficial effects of beta-activation, while high dose (which has off-target sodium channel effects) decreased arrhythmia susceptibility. These results demonstrate that beta-activation may be protective in LQT3 and help to reconcile seemingly conflicting results from different experimental models. They also highlight the need for well-controlled clinical investigations re-evaluating the use of beta-blockers in LQT3 patients.

Transfer-printing of active layers to achieve high quality interfaces in sequentially deposited multilayer inverted polymer solar cells fabricated in air

PubMed Central

Vohra, Varun; Anzai, Takuya; Inaba, Shusei; Porzio, William; Barba, Luisa

2016-01-01

Abstract Polymer solar cells (PSCs) are greatly influenced by both the vertical concentration gradient in the active layer and the quality of the various interfaces. To achieve vertical concentration gradients in inverted PSCs, a sequential deposition approach is necessary. However, a direct approach to sequential deposition by spin-coating results in partial dissolution of the underlying layers which decreases the control over the process and results in not well-defined interfaces. Here, we demonstrate that by using a transfer-printing process based on polydimethylsiloxane (PDMS) stamps we can obtain increased control over the thickness of the various layers while at the same time increasing the quality of the interfaces and the overall concentration gradient within the active layer of PSCs prepared in air. To optimize the process and understand the influence of various interlayers, our approach is based on surface free energy, spreading parameters and work of adhesion calculations. The key parameter presented here is the insertion of high quality hole transporting and electron transporting layers, respectively above and underneath the active layer of the inverted structure PSC which not only facilitates the transfer process but also induces the adequate vertical concentration gradient in the device to facilitate charge extraction. The resulting non-encapsulated devices (active layer prepared in air) demonstrate over 40% increase in power conversion efficiency with respect to the reference spin-coated inverted PSCs. PMID:27877901

Design, synthesis, and in vitro transfection biology of novel tocopherol based monocationic lipids: a structure-activity investigation.

PubMed

Kedika, Bhavani; Patri, Srilakshmi V

2011-01-27

Herein, we report on the design, synthesis, and in vitro gene delivery efficacies of five novel tocopherol based cationic lipids (1-5) in transfecting CHO, B16F10, A-549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids (1-5) were evaluated by both β-galactosidase reporter gene expression and inverted fluorescent microscopic experiments. The results of the present structure-activity investigation convincingly demonstrate that the tocopherol based lipid with three hydroxyl groups in its headgroup region showed 4-fold better transfection efficiency than the commercial formulation. The results also demonstrate that these tocopherol based lipids may be targeted to liver. Transfection efficiency of all the relevant lipids was maintained even when the serum was present during the transfection conditions. The results indicated that the designed systems are quite capable of transferring the DNA into all four types of cells studied with low or no toxicity.

Methodology and Baseline Results From the Evaluation of a Sexuality Education Activity in Mpumalanga and KwaZulu-Natal, South Africa.

PubMed

Speizer, Ilene S; Mandal, Mahua; Xiong, Khou; Hattori, Aiko; Makina-Zimalirana, Ndinda; Kumalo, Faith; Taylor, Stephen; Ndlovu, Muzi S; Madibane, Mathata; Beke, Andy

2018-04-01

In South Africa, adolescents and young adults (ages 15-24) are at risk of HIV, sexually transmitted infections, and unintended pregnancies. Recently, the Department of Basic Education has revised its sexuality education content and teaching strategies (using scripted lessons plans) as part of its life orientation curriculum. This paper presents the methodology and baseline results from the evaluation of the scripted lesson plans and supporting activities. A rigorous cluster-level randomized design with random assignment of schools as clusters is used for the evaluation. Baseline results from grade 8 female and male learners and grade 10 female learners demonstrate that learners are at risk of HIV and early and unintended pregnancies. Multivariable analyses demonstrate that household-level food insecurity and living with an HIV-positive person are associated with sexual experience and pregnancy experience. Implications are discussed for strengthening the current life orientation program for future scale-up by the government of South Africa.

Antidyslipidemic and Antioxidant Activities of Hibiscus rosa sinensis Root Extract in Alloxan Induced Diabetic Rats.

PubMed

Kumar, Vishnu; Mahdi, Farzana; Khanna, Ashok Kumar; Singh, Ranjana; Chander, Ramesh; Saxena, Jitendra Kumar; Mahdi, Abbas Ali; Singh, Raj Kumar

2013-01-01

The antidyslipidemic activity of Hibiscus rosa sinensis (Malvaceae) root extract has been studied in alloxan induced diabetic rats. In this model, oral administration of root extract (500 mg/kg bw. p.o.) for 15 days resulted in significant decreased in the levels of blood glucose, plasma lipids and reactivated post heparin lipoprotein lipase activity in alloxan induced diabetic rats. Furthermore, the root extract (50-500 μg) when tested for its antioxidant activity, inhibited the generation of super oxide anions and hydroxyl radicals, in both enzymic and non enzymic systems in vitro. The results of the present study demonstrated antidyslipidemic and antioxidant activities in root extract of H. rosa sinensis which could be used in prevention of diabetic-dyslipidemia and related complications.

Long-term continuous monitor demonstration program: Columbus and Southern Ohio Electric Company, Conesville Unit 6. Final report Dec 79-Mar 83

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

Peduto, E.F. Jr.; Porter, T.J.; Midgley, D.P.

1984-03-01

The report gives results of a continuous monitoring demonstration at the Columbus and Southern Ohio Electric Company's Conesville Generating Station. The purpose of the demonstration was to determine the feasibility of the requirements for monitoring and control of SO2 emissions as specified in 40 CFR, Part 60, Subpart Da, which promulgates new source performance standards (NSPS) for new utility steam generators. A secondary objective was to adhere to the draft quality assurance requirements scheduled for promulgation as Appendix F. The report describes program activities and results of the field portion, during which data were collected for about 12 months ofmore » a 16-month period.« less

Further Examination of the Vibratory Loads Reduction Results from the NASA/ARMY/MIT Active Twist Rotor Test

NASA Technical Reports Server (NTRS)

Wilbur, Matthew L.; Yeager, William T., Jr.; Sekula, Martin K.

2002-01-01

The vibration reduction capabilities of a model rotor system utilizing controlled, strain-induced blade twisting are examined. The model rotor blades, which utilize piezoelectric active fiber composite actuators, were tested in the NASA Langley Transonic Dynamics Tunnel using open-loop control to determine the effect of active-twist on rotor vibratory loads. The results of this testing have been encouraging, and have demonstrated that active-twist rotor designs offer the potential for significant load reductions in future helicopter rotor systems. Active twist control was found to use less than 1% of the power necessary to operate the rotor system and had a pronounced effect on both rotating- and fixed-system loads, offering reductions in individual harmonic loads of up to 100%. A review of the vibration reduction results obtained is presented, which includes a limited set of comparisons with results generated using the second-generation version of the Comprehensive Analytical Model of Rotorcraft Aerodynamics and Dynamics (CAMRAD II) rotorcraft comprehensive analysis.

High targeted migration of human mesenchymal stem cells grown in hypoxia is associated with enhanced activation of RhoA

PubMed Central

2013-01-01

Introduction A feature which makes stem cells promising candidates for cell therapy is their ability to migrate effectively into damaged or diseased tissues. Recent reports demonstrated the increased motility of human mesenchymal stem cells (hMSC) grown under hypoxic conditions compared to normoxic cells. However, the directional migration of hMSC cultured in hypoxia has not been investigated. In this study we examined the in vitro transmembrane migration of hMSC permanently cultured in hypoxia in response to various cytokines. We also studied the involvement of RhoA, a molecule believed to play an essential role in the migration of MSC via reorganization of the cytoskeleton. Methods We compared the directional migration of human hMSCs grown permanently under normal (21%, normoxic) and low O2 (5%, hypoxic) conditions until passage 4 using an in vitro transmembrane migration assay. A series of 17 cytokines was used to induce chemotaxis. We also compared the level of GTP-bound RhoA in the cell extracts of calpeptin-activated hypoxic and normoxic hMSC. Results We found that hMSC cultured in hypoxia demonstrate markedly higher targeted migration activity compared to normoxic cells, particularly towards wound healing cytokines, including those found in ischemic and myocardial infarction. We also demonstrated for the first time that hMSC are dramatically more sensitive to activation of RhoA. Conclusions The results of this study indicate that high directional migration of hMSCs permanently grown in hypoxia is associated with the enhanced activation of RhoA. The enhanced migratory capacity of hypoxic hMSC would further suggest their potential advantages for clinical applications. PMID:23295150

β-Subunit of the Ostα-Ostβ Organic Solute Transporter Is Required Not Only for Heterodimerization and Trafficking but Also for Function*

PubMed Central

Christian, Whitney V.; Li, Na; Hinkle, Patricia M.; Ballatori, Nazzareno

2012-01-01

The organic solute transporter, Ost/Slc51, is composed of two distinct proteins that must heterodimerize to generate transport activity, but the role of the individual subunits in mediating transport activity is unknown. The present study identified regions in Ostβ required for heterodimerization with Ostα, trafficking of the Ostα-Ostβ complex to the plasma membrane, and bile acid transport activity in HEK293 cells. Bimolecular fluorescence complementation analysis revealed that a 25-amino acid peptide containing the Ostβ transmembrane (TM) domain heterodimerized with Ostα, although the resulting complex failed to reach the plasma membrane and generate cellular [3H]taurocholate transport activity. Deletion of the single TM domain of Ostβ abolished interaction with Ostα, demonstrating that the TM segment is necessary and sufficient for formation of a heteromeric complex with Ostα. Mutation of the highly conserved tryptophan-asparagine sequence within the TM domain of Ostβ to alanines did not prevent cell surface trafficking, but abolished transport activity. Removal of the N-terminal 27 amino acids of Ostβ resulted in a transporter complex that reached the plasma membrane and exhibited transport activity at 30 °C. Complete deletion of the C terminus of Ostβ abolished [3H]taurocholate transport activity, but reinsertion of two native arginines immediately C-terminal to the TM domain rescued this defect. These positively charged residues establish the correct Nexo/Ccyt topology of the peptide, in accordance with the positive inside rule. Together, the results demonstrate that Ostβ is required for both proper trafficking of Ostα and formation of the functional transport unit, and identify specific residues of Ostβ critical for these processes. PMID:22535958

DREADD in parvalbumin interneurons of the dentate gyrus modulates anxiety, social interaction and memory extinction.

PubMed

Zou, D; Chen, L; Deng, D; Jiang, D; Dong, F; McSweeney, C; Zhou, Y; Liu, L; Chen, G; Wu, Y; Mao, Y

2016-01-01

Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.

Evaluation of radical scavenging activity, intestinal cell viability and antifungal activity of Brazilian propolis by-product.

PubMed

de Francisco, Lizziane; Pinto, Diana; Rosseto, Hélen; Toledo, Lucas; Santos, Rafaela; Tobaldini-Valério, Flávia; Svidzinski, Terezinha; Bruschi, Marcos; Sarmento, Bruno; Oliveira, M Beatriz P P; Rodrigues, Francisca

2018-03-01

Propolis is a natural adhesive resinous compound produced by honeybees to protect hives from bacteria and fungi, being extremely expensive for food industry. During propolis production, a resinous by-product is formed. This resinous waste is currently undervalued and underexploited. Accordingly, in this study the proximate physical and chemical quality, as well as the antioxidant activity, radical scavenging activity and cell viability of this by-product were evaluated and compared with propolis in order to boost new applications in food and pharmaceutical industries. The results revealed that the by-product meets the physical and chemical quality standards expected and showed that the propolis waste contains similar amounts of total phenolic content (TPC) and total flavonoid content (TFC) to propolis. Also, a good scavenging activity against reactive oxygen and nitrogen species (ROS and RNS, respectively) determined by the assays of superoxide anion radical (O 2 - ), hydrogen peroxide (H 2 O 2 ), hypochlorous acid (HOCl), nitric oxide (NO) and peroxyl radical (ROO) were determined. Linear positive correlations were established between the TPC of both samples and the antioxidant activity evaluated by three different methods (DPPH, ABTS and FRAP assays). The extracts were also screened for cell viability assays in two different intestinal cell lines (HT29-MTX and Caco-2), showing a viability concentration-dependent. Similarly, the Artemia salina assay, used to assess toxicity, demonstrated the concentration influence on results. Finally, the antifungal activity against ATCC species of Candida was demonstrated. These results suggest that propolis by-product can be used as a new rich source of bioactive compounds for different areas, such as food or pharmaceutical. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term behavioral consequences of prenatal MDMA exposure.

PubMed

Thompson, Valerie B; Heiman, Justin; Chambers, James B; Benoit, Stephen C; Buesing, William R; Norman, Mantana K; Norman, Andrew B; Lipton, Jack W

2009-03-23

The current study sought to determine whether prenatal 3,4-methylenedioxy-N-methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral sequelae in adult offspring. Prenatal MDMA exposure results in increased dopaminergic fiber density in the prefrontal cortex, striatum and nucleus accumbens of young rats. Since these areas are critical in response to novelty, reward, attention and locomotor activity, we hypothesized that prenatal MDMA exposure would produce significant changes in the performance of tasks that examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA exhibited greater activity and spent more time in the center during a novel open field test as compared to controls. This increased activity was not reflected in normal home cage activity. Prenatal exposure to MDMA did not affect feeding or food reward. It did not alter cocaine self-administration behaviors, nor did it have an effect on the locomotor response to amphetamine challenge. Finally, while prenatal MDMA did not affect performance in the radial arm maze or the Morris water maze (MWM), these animals demonstrated altered performance in a cued MWM paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a hanging cue when the platform in the MWM was removed as compared to controls. Together, these data demonstrate that prenatal exposure to MDMA results in a behavioral phenotype in adult rats characterized by reduced anxiety, a heightened response to novelty, and "hyperattentiveness" to environmental cues during spatial learning.

Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation.

PubMed

Karimpour, Shervin; Lou, Junyang; Lin, Lilie L; Rene, Luis M; Lagunas, Lucio; Ma, Xinrong; Karra, Sreenivasu; Bradbury, C Matthew; Markovina, Stephanie; Goswami, Prabhat C; Spitz, Douglas R; Hirota, Kiichi; Kalvakolanu, Dhananjaya V; Yodoi, Junji; Gius, David

2002-09-12

A recently identified class of signaling factors uses critical cysteine motif(s) that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific signal transduction cascades regulating downstream proteins with similar redox-sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1) and transcription factors such as the AP-1 complex both contain redox-sensitive cysteine motifs that regulate activity in response to oxidative stress. The mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine-containing flavoprotein that also appears to regulate multiple downstream intracellular redox-sensitive proteins. Since ionizing radiation (IR) induces oxidative stress as well as increases AP-1 DNA-binding activity via the activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the regulation of AP-1 activity in response to IR were investigated. Permanently transfected cell lines that overexpress wild type TR demonstrated constitutive increases in AP-1 DNA-binding activity as well as AP-1-dependent reporter gene expression, relative to vector control cells. In contrast, permanently transfected cell lines expressing a TR gene with the active site cysteine motif deleted were unable to induce AP-1 activity or reporter gene expression in response to IR. Transient genetic overexpression of either the TR wild type or dominant-negative genes demonstrated similar results using a transient assay system. One mechanism through which TR regulates AP-1 activity appears to involve TRX sub-cellular localization, with no change in the total TRX content of the cell. These results identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein.

Using the virtual brain to reveal the role of oscillations and plasticity in shaping brain's dynamical landscape.

PubMed

Roy, Dipanjan; Sigala, Rodrigo; Breakspear, Michael; McIntosh, Anthony Randal; Jirsa, Viktor K; Deco, Gustavo; Ritter, Petra

2014-12-01

Spontaneous brain activity, that is, activity in the absence of controlled stimulus input or an explicit active task, is topologically organized in multiple functional networks (FNs) maintaining a high degree of coherence. These "resting state networks" are constrained by the underlying anatomical connectivity between brain areas. They are also influenced by the history of task-related activation. The precise rules that link plastic changes and ongoing dynamics of resting-state functional connectivity (rs-FC) remain unclear. Using the framework of the open source neuroinformatics platform "The Virtual Brain," we identify potential computational mechanisms that alter the dynamical landscape, leading to reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that network activity in the absence of plasticity is characterized by irregular oscillations between low-amplitude asynchronous states and high-amplitude synchronous states. We then demonstrate the capability of spike-timing-dependent plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to efficiently influence learning. Further, we show how alpha-state-dependent STDP alters the local area dynamics from an irregular to a highly periodic alpha-like state. This is an important finding, as the cortical input from the thalamus is at the rate of alpha. We demonstrate how resulting rhythmic cortical output in this frequency range acts as a neuronal tuner and, hence, leads to synchronization or de-synchronization between brain areas. Finally, we demonstrate that locally restricted structural connectivity changes influence local as well as global dynamics and lead to altered rs-FC.

Design, synthesis, antibacterial activity and docking study of some new trimethoprim derivatives.

PubMed

Rashid, Umer; Ahmad, Waqas; Hassan, Syed Fahad; Qureshi, Naveeda Akhtar; Niaz, Basit; Muhammad, Bakhtiar; Imdad, Sameera; Sajid, Muhammad

2016-12-01

In present study, nineteen novel trimethoprim (TMP) derivatives were designed, synthesized and evaluated for their antibacterial potential. Hydroxy trimethoprim 2 (HTMP) was synthesized by following the demethylation of 4-methoxy group at trimethoxy benzyl ring of TMP. Structure-activity relationship (SAR) studies were explored on HTMP by incorporating various substituents leading to the identification of some new compounds with improved antibacterial activities. The results revealed that the introduction of benzyloxy (4a-e) and phenyl ethanone (5a-e) group at 4-position of dimethoxy benzyl ring leads to overall increase in the antibacterial activity. The most potent antibacterial compound discovered is benzyloxy derivative 4b with MIC value of 5.0μM against Staphylococcus aureus and 4.0μM against Escherichia coli strains higher than the standard TMP (22.7μM against S. aureus and 55.1μM against E. coli). Substitution at 4-NH 2 group was not tolerated and the resulting Schiff base derivatives 3a-h demonstrated very little or no antibacterial activity in the tested concentration domain. We further performed exploratory docking studies on dihydrofolate reductase (DHFR) to rationalize the in vitro biological data and to demonstrate the mechanism of antibacterial activity. For the ability to cross lipophilic outer membrane, logP was computed. It was found that the compounds possessing high hydrophobicity have high activity against E. coli. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

PubMed Central

Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

2006-01-01

Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [3H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases. PMID:16951716

Activation of aryl hydrocarbon receptor regulates the LPS/IFNγ-induced inflammatory response by inducing ubiquitin-proteosomal and lysosomal degradation of RelA/p65.

PubMed

Domínguez-Acosta, O; Vega, L; Estrada-Muñiz, E; Rodríguez, M S; Gonzalez, F J; Elizondo, G

2018-06-21

Several studies have identified the aryl hydrocarbon receptor (AhR) as a negative regulator of the innate and adaptive immune responses. However, the molecular mechanisms by which this transcription factor exerts such modulatory effects are not well understood. Interaction between AhR and RelA/p65 has previously been reported. RelA/p65 is the major NFκB subunit that plays a critical role in immune responses to infection. The aim of the present study was to determine whether the activation of AhR disrupted RelA/p65 signaling in mouse peritoneal macrophages by decreasing its half-life. The data demonstrate that the activation of AhR by TCDD and β-naphthoflavone (β-NF) decreased protein levels of the pro-inflammatory cytokines TFN-α, IL-6 and IL-12 after macrophage activation with LPS/IFNγ. In an AhR-dependent manner, TCDD treatment induces RelA/p65 ubiquitination and proteosomal degradation, an effect dependent on AhR transcriptional activity. Activation of AhR also induced lysosome-like membrane structure formation in mouse peritoneal macrophages and RelA/p65 lysosome-dependent degradation. In conclusion, these results demonstrate that AhR activation promotes RelA/p65 protein degradation through the ubiquitin proteasome system, as well as through the lysosomes, resulting in decreased pro-inflammatory cytokine levels in mouse peritoneal macrophages. Copyright © 2018. Published by Elsevier Inc.

Cardiac glycoside ouabain induces activation of ATF-1 and StAR expression by interacting with the α4 isoform of the sodium pump in Sertoli cells.

PubMed

Dietze, Raimund; Konrad, Lutz; Shihan, Mazen; Kirch, Ulrike; Scheiner-Bobis, Georgios

2013-03-01

Sertoli cells express α1 and α4 isoforms of the catalytic subunit of Na(+),K(+)-ATPase (sodium pump). Our recent findings demonstrated that interactions of the α4 isoform with cardiotonic steroids (CTS) like ouabain induce signaling cascades that resemble the so-called non-classical testosterone pathway characterized by activation of the c-Src/c-Raf/Erk1/2/CREB signaling cascade. Here we investigate a possible physiological significance of the activated cascade. The results obtained in the current investigation show that the ouabain-induced signaling cascade also leads to the activation of the CREB-related activating transcription factor 1 (ATF-1) in the Sertoli cell line 93RS2 in a concentration- and time-dependent manner, as demonstrated by detection of ATF-1 phosphorylated on Ser63 in western blots. The ouabain-activated ATF-1 protein was found to localize to the cell nuclei. The sodium pump α4 isoform mediates this activation, as it is ablated when cells are incubated with siRNA to the α4 isoform. Ouabain also leads to increased expression of steroidogenic acute regulator (StAR) protein, which has been shown to be a downstream consequence of CREB/ATF-1 activation. Taking into consideration that CTS are most likely produced endogenously, the demonstrated induction of StAR expression by ouabain establishes a link between CTS, the α4 isoform of the sodium pump, and steroidogenesis crucial for male fertility and reproduction. Copyright © 2012 Elsevier B.V. All rights reserved.

Active inclusion bodies of acid phosphatase PhoC: aggregation induced by GFP fusion and activities modulated by linker flexibility

PubMed Central

2013-01-01

Background Biologically active inclusion bodies (IBs) have gained much attention in recent years. Fusion with IB-inducing partner has been shown to be an efficient strategy for generating active IBs. To make full use of the advantages of active IBs, one of the key issues will be to improve the activity yield of IBs when expressed in cells, which would need more choices on IB-inducing fusion partners and approaches for engineering IBs. Green fluorescent protein (GFP) has been reported to aggregate when overexpressed, but GFP fusion has not been considered as an IB-inducing approach for these fusion proteins so far. In addition, the role of linker in fusion proteins has been shown to be important for protein characteristics, yet impact of linker on active IBs has never been reported. Results Here we report that by fusing GFP and acid phosphatase PhoC via a linker region, the resultant PhoC-GFPs were expressed largely as IBs. These IBs show high levels of specific fluorescence and specific PhoC activities (phosphatase and phosphotransferase), and can account for up to over 80% of the total PhoC activities in the cells. We further demonstrated that the aggregation of GFP moiety in the fusion protein plays an essential role in the formation of PhoC-GFP IBs. In addition, PhoC-GFP IBs with linkers of different flexibility were found to exhibit different levels of activities and ratios in the cells, suggesting that the linker region can be utilized to manipulate the characteristics of active IBs. Conclusions Our results show that active IBs of PhoC can be generated by GFP fusion, demonstrating for the first time the potential of GFP fusion to induce active IB formation of another soluble protein. We also show that the linker sequence in PhoC-GFP fusion proteins plays an important role on the regulation of IB characteristics, providing an alternative and important approach for engineering of active IBs with the goal of obtaining high activity yield of IBs. PMID:23497261

Design, synthesis, antiviral bioactivity and three-dimensional quantitative structure-activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety.

PubMed

Wu, Zengxue; Zhang, Jian; Chen, Jixiang; Pan, Jianke; Zhao, Lei; Liu, Dengyue; Zhang, Awei; Chen, Jin; Hu, Deyu; Song, Baoan

2017-10-01

Ferulic acid and quinazoline derivatives possess good antiviral activities. In order to develop novel compounds with high antiviral activities, a series of ferulic acid ester derivatives containing quinazoline were synthesized and evaluated for their antiviral activities. Bioassays indicated that some of the compounds exhibited good antiviral activities in vivo against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). One of the compounds demonstrated significant curative and protective activities against TMV and CMV, with EC 50 values of 162.14, 114.61 and 255.49, 138.81 mg L -1 , respectively, better than those of ningnanmycin (324.51, 168.84 and 373.88, 272.70 mg L -1 ). The values of q 2 and r 2 for comparative molecular field analysis and comparative molecular similarity index analysis in the TMV (0.508, 0.663 and 0.992, 0.930) and CMV (0.530, 0.626 and 0.997, 0.981) models presented good predictive abilities. Some of the title compounds demonstrated good antiviral activities. Three-dimensional quantitative structure-activity relationship models revealed that the antiviral activities depend on steric and electrostatic properties. These results could provide significant structural insights for the design of highly active ferulic acid derivatives. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Activation of p300 histone acetyltransferase activity and acetylation of the androgen receptor by bombesin in prostate cancer cells.

PubMed

Gong, J; Zhu, J; Goodman, O B; Pestell, R G; Schlegel, P N; Nanus, D M; Shen, R

2006-03-30

Androgen receptor signaling in prostate cancer cells is augmented by the androgen receptor (AR) coactivator p300, which transactivates and acetylates the AR in the presence of dihydrotestosterone (DHT). As prostate cancer (PC) cells progress to androgen independence, AR signaling remains intact, indicating that other factors stimulate AR activities in the absence of androgen. We previously reported that neuropeptide growth factors could transactivate the AR in the presence of very low concentrations of DHT. Here, we examine the involvement of p300 in neuropeptide activation of AR signaling. Transfection of increasing concentrations of p300 in the presence of bombesin into PC-3 cells resulted in a linear increase in AR transactivation, suggesting that p300 acts as a coactivator in neuropeptide-mediated AR transactivation. P300 is endowed with histone acetyltransferase (HAT) activity. Therefore, we examine the effect of bombesin on p300 HAT activity. At 4 h after the addition of bombesin, p300 HAT activity increased 2.0-fold (P<0.01). Incubation with neutral endopeptidase, which degrades bombesin, or bombesin receptor antagonists blocked bombesin-induced p300 HAT activity. To explore the potential signaling pathways involved in bombesin-induced p300 HAT activity, we examined Src and PKCdelta pathways that mediate bombesin signaling. Inhibitors of Src kinase activity or Src kinase siRNA blocked bombesin-induced p300 HAT activity, whereas PKCdelta inhibitors or PKCdelta siRNA significantly increased bombesin-induced p300 HAT activity suggesting that Src kinase and PKCdelta kinase are involved in the regulation of p300 HAT activity. As AR is acetylated in the presence of 100 nM DHT, we next examined whether bombesin-induced p300 HAT activity would result in enhanced AR acetylation. Bombesin-induced AR acetylation at the same motif KLKK observed in DHT-induced acetylation. Elimination of p300 using p300 siRNA reduced AR acetylation, demonstrating that AR acetylation was mediated by p300. AR acetylation results in AR transactivation and the expression of the AR-regulated gene prostate-specific antigen (PSA). Therefore, we examined bombesin-induced AR transactivation and PSA expression in the presence and absence of p300 siRNA and found inhibition of p300 expression reduced bombesin-induced AR transactivation and PSA expression. Together these results demonstrate that bombesin, via Src and PKCdelta signaling pathways, activates p300 HAT activity which leads to enhanced acetylation of AR resulting in increased expression of AR-regulated genes.

Structure of nanoporous carbon materials for supercapacitors

NASA Astrophysics Data System (ADS)

Volperts, A.; Mironova-Ulmane, N.; Sildos, I.; Vervikishko, D.; Shkolnikov, E.; Dobele, G.

2012-08-01

Activated carbons with highly developed porous structure and nanosized pores (8 - 11 Å) were prepared from alder wood using thermochemical activation method with sodium hydroxide. Properties of the obtained activated carbons were examined by benzene and nitrogen sorption, X-Ray diffraction and Raman spectroscopy. Tests of activated carbons as electrodes in supercapacitors were performed as well. It was found that specific surface area of above mentioned activated carbons was 1800 m2/g (Dubinin - Radushkevich). Raman spectroscopy demonstrated the presence of ordered and disordered structures of graphite origin. The performance of activated carbons as electrodes in supercapacitors have shown superior results in comparison with electrodes made with commercial carbon tissues.

Optimal active vibration absorber: Design and experimental results

NASA Technical Reports Server (NTRS)

Lee-Glauser, Gina; Juang, Jer-Nan; Sulla, Jeffrey L.

1992-01-01

An optimal active vibration absorber can provide guaranteed closed-loop stability and control for large flexible space structures with collocated sensors/actuators. The active vibration absorber is a second-order dynamic system which is designed to suppress any unwanted structural vibration. This can be designed with minimum knowledge of the controlled system. Two methods for optimizing the active vibration absorber parameters are illustrated: minimum resonant amplitude and frequency matched active controllers. The Controls-Structures Interaction Phase-1 Evolutionary Model at NASA LaRC is used to demonstrate the effectiveness of the active vibration absorber for vibration suppression. Performance is compared numerically and experimentally using acceleration feedback.

Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

PubMed Central

Rea, Mary C.; Dobson, Alleson; O'Sullivan, Orla; Crispie, Fiona; Fouhy, Fiona; Cotter, Paul D.; Shanahan, Fergus; Kiely, Barry; Hill, Colin; Ross, R. Paul

2011-01-01

Vancomycin, metronidazole, and the bacteriocin lacticin 3147 are active against a wide range of bacterial species, including Clostridium difficile. We demonstrate that, in a human distal colon model, the addition of each of the three antimicrobials resulted in a significant decrease in numbers of C. difficile. However, their therapeutic use in the gastrointestinal tract may be compromised by their broad spectrum of activity, which would be expected to significantly impact on other members of the human gut microbiota. We used high-throughput pyrosequencing to compare the effect of each antimicrobial on the composition of the microbiota. All three treatments resulted in a decrease in the proportion of sequences assigned to the phyla Firmicutes and Bacteroidetes, with a corresponding increase in those assigned to members of the Proteobacteria. One possible means of avoiding such “collateral damage” would involve the application of a narrow-spectrum antimicrobial with specific anti-C. difficile activity. We tested this hypothesis using thuricin CD, a narrow-spectrum bacteriocin produced by Bacillus thuringiensis, which is active against C. difficile. The results demonstrated that this bacteriocin was equally effective at killing C. difficile in the distal colon model but had no significant impact on the composition of the microbiota. This offers the possibility of developing a targeted approach to eliminating C. difficile in the colon, without collateral damage. PMID:20616009

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

PubMed Central

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

2016-01-01

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

Increased autophagy in fibroblast-like synoviocytes leads to immune enhancement potential in rheumatoid arthritis.

PubMed

Yang, Ru; Zhang, Yingzi; Wang, Lin; Hu, Ji; Wen, Jian; Xue, Leixi; Tang, Mei; Liu, Zhichun; Fu, Jinxiang

2017-02-28

The incidence of rheumatoid arthritis (RA) has been reported to be correlated with a disorder of immunregulation. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play an important role in regulating the local immune microenvironment. However, the potential mechanism of RA-FLS in regulating the immnue response is not clearly understood. In this study, we demonstrated that the expression of HIF-1α was significantly up-regulated in rheumatoid arthritis tissue which indicated that the hypoxia condition in the microenvironment. We also observed that RA-FLSs demonstrated the potential to up-regulate immune activation. Meanwhile, the level of autophagy increased in RA-FLSs compared with control group. Besides that, the expression of IL-6 was up-regulated not only in RA-FLSs but also in the fibroblasts that treated with hypoxia condition. Accordingly, we found that autophagy inhibitiors could effectively inhibit the immune activation function of RA-FLSs medicated by IL-6. Taken together, the results we demonstrated above indicated that the hypoxia microenvironment could effectively induce the incidence of autophagy and then lead to the immune activation function of RA-FLSs medicated by IL-6.

How-To-Do-It: Measuring Vegetation Biomass and Production.

ERIC Educational Resources Information Center

Collins, Don; Weaver, T.

1988-01-01

Describes a lab exercise used to demonstrate the measurement of biomass in a three layered forest. Discusses sampling, estimation methods, and the analysis of results. Presents an example of a summary sheet for this activity. (CW)

ACID/HEAVY METAL TOLERANT PLANTS

EPA Science Inventory

This report summarizes the results of Mine Waste Technology Program (MWTP) Activity III, Project 30. The objective of Project 30 was to select populations (i.e., ecotypes) from native, indigenous plant species that demonstrate superior growth characteristics and sustainability on...

In vitro interaction between SURFACEN® and surfactant protein A against Leishmania amazonensis.

PubMed

de Guevara, Yuliannis Lugones Ladrón; Hidalgo, Odalys Blanco; Faure, Roberto; Fidalgo, Lianet Monzote

2013-01-01

Leishmaniasis is caused by a parasite of the Leishmania genus, affecting more than 12 million people in 98 countries. The control of leishmaniasis remains a serious problem. There are currently no vaccines for leishmaniasis. The drugs available are toxic, expensive and frequently ineffective. The in vitro activity of SURFACEN® and SP-A against Leishmania amazonensis was evaluated. The combination of both products resulted in a synergic pharmacology effect, demonstrated by a fractional inhibitory concentration index <0.5. A more effective combination was a SURFACEN/SP-A ratio of 4:1, using a method of fixed ratio. The therapeutic effect of SURFACEN and SP-A as antileishmanial compounds was demonstrated, with a potentiation of activity when they were incubated in conjunction. Our results propose an exploration of these products in order to design new formulations against the Leishmania parasite. © 2014 S. Karger AG, Basel.

Substituent Effects on Desferrithiocin and Desferrithiocin Analogue Iron Clearing and Toxicity Profiles

PubMed Central

Bergeron, Raymond J.; Wiegand, Jan; Bharti, Neelam; McManis, James S.

2012-01-01

Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto the aromatic ring resulted in orally active iron chelators that were much less toxic than 1. The purpose of the current study was to determine if a comparable reduction in renal toxicity could be achieved by performing the same structural manipulations on 1 itself. Accordingly, three DFT analogues were synthesized. Iron clearing efficiency and ferrokinetics were evaluated in rats and primates; toxicity assessments were carried out in rodents. The resulting DFT ligands demonstrated a reduction in toxicity that was equivalent to that of the DADFT analogues and presented with excellent iron clearing properties. PMID:22889170

Dimers of coumarin-1,2,3-triazole hybrids bearing alkyl spacer: Design, microwave-assisted synthesis, molecular docking and evaluation as antimycobacterial and antimicrobial agents

NASA Astrophysics Data System (ADS)

Ashok, Dongamanti; Gundu, Srinivas; Aamate, Vikas Kumar; Devulapally, Mohan Gandhi; Bathini, Raju; Manga, Vijjulatha

2018-04-01

The present study demonstrated the synthesis of new series of coumarin-1,2,3-triazole hybrids under microwave irradiation method. Several dimers of coumarin based 1,2,3-triazole derivatives were synthesized and their antimycobacterial and antimicrobial activities were investigated. The antimycobacterial activity screening results revealed that compounds 6i and 6j were the most active against Mycobacterium tuberculosis H37Rv strain. The active compounds were further evaluated for cytotoxicity with HEK cell lines and exhibited less % of inhibition. The same synthetic hybrids were evaluated for their antimicrobial activity against various bacterial strains and fungal strains and compounds 6e, 6h, 6i and 6j were found to be the most promising antimicrobial potent molecules. Furthermore, the active compounds against Mycobacterium tuberculosis were evaluated for their molecular docking studies against pantothenate synthetase (PS) enzyme of MTB and the docking results are in well agreement with the antitubercular evaluation results.

Indoor Tracking to Understand Physical Activity and Sedentary Behaviour: Exploratory Study in UK Office Buildings

PubMed Central

Spinney, Richard; Smith, Lee; Ucci, Marcella; Fisher, Abigail; Konstantatou, Marina; Sawyer, Alexia; Wardle, Jane; Marmot, Alexi

2015-01-01

Little is known of the patterns of physical activity, standing and sitting by office workers. However, insight into these behaviours is of growing interest, notably in regard to public health priorities to reduce non-communicable disease risk factors associated with high levels of sitting time and low levels of physical activity. With the advent and increasing availability of indoor tracking systems it is now becoming possible to build detailed pictures of the usage of indoor spaces. This paper reports initial results of indoor tracking used in conjunction with the ActivPAL activity monitoring device. In this paper we give an overview of the usage of the tracking system and its installation and illustrate some of the resultant data. We also provide preliminary results that investigate the relationship between location, light physical activity and sitting in a small sample of office workers (n=33) from two separate office environments in order to demonstrate the relevance and explanatory power of the technique. PMID:25993515

Explosive volcanism lessons learned from Mentos and soda eruptions

NASA Astrophysics Data System (ADS)

Wright, H. M.; Rust, A. C.; Cashman, K. V.

2006-12-01

When hard Mentos candies are dropped into a bottle of carbonated beverage, the resultant rapid CO2 exsolution and gas expansion causes an impressive soda `eruption'. We explore the ways in which this simple example can be used to demonstrate explosive volcanic processes. Through hands-on experiments, students can vary the type of candy, the type of beverage, and the shape of the vent (by making a hole in the cap of the soda bottle) to understand the processes that are influencing the height and duration of the eruption column. The activity can be tailored to demonstrate basic principles of gas exsolution and expansion for young students, but can also be extended to more complex principles of heterogeneous bubble nucleation and decreasing surface tension for college students. We present results from Mentos and soda experiments by a group of college freshman in the elementary education program (with no real science background). We compare students' resultant understanding of the similarities and differences between volcanic eruptions and the experiments with the results from a similar activity performed by a group of graduate geology students. The Mentos and soda reaction is dramatic. Video clips of people, young and old, trying this experiment across the world can be found on the world wide web. We suggest that the popularity of this demonstration be used to help teach fundamental concepts in both volcanology and scientific experimentation.

An in vitro cytotoxicity assessment of graphene nanosheets on alveolar cells

NASA Astrophysics Data System (ADS)

Dervin, Saoirse; Murphy, James; Aviles, Ruth; Pillai, Suresh C.; Garvey, Mary

2018-03-01

The collection of intrinsic properties possessed by graphene family nanomaterials (GFNs) results in their continuous exploitation for biomedical applications. The materials biomedical potential has motivated an upsurge in green preparation routes for the production of graphene like materials with limited toxicity. A number of bio-friendly reducing agents have been utilized for the preparation of chemically reduced graphene oxide (GO), and their resulting cytotoxic effects examined. However, the toxicology effects of one of the first biomolecules implemented for the reduction of GO, ascorbic acid (AA) has yet to be investigated. Herein, the toxicity of three distinct GFNs; GO, hydrazine reduced GO (H.rGO) and AA.rGO, prepared through diverse chemical routes are studied, to demonstrate the cytotoxic activity of a green reducer, in comparison to an established reduction method using hydrazine hydrate. The variation in atomic structure of GO, H.rGO and AA.rGO resulting from different synthesis techniques demonstrates the dependence of toxicity on particle shape and size. All GFNs induced high levels of alveolar cell toxicity. Interaction of AA.rGO with the A549 human lung epithelial carcinoma cell line resulted in increased leakage of lactate dehydrogenase, indicative of diminished cell membrane integrity. The uncharacteristic shape of the AA.rGO may be responsible for this proliferated release of the essential protein. The presented data therefore demonstrates that modification of synthetic processes significantly alter the biological activities of GFNs.

An Improved Method for Demonstrating Visual Selection by Wild Birds.

ERIC Educational Resources Information Center

Allen, J. A.; And Others

1990-01-01

An activity simulating natural selection in which wild birds are predators, green and brown pastry "baits" are prey, and trays containing colored stones as the backgrounds is presented. Two different methods of measuring selection are used to describe the results. The materials and methods, results, and discussion are included. (KR)

Human cortical activity evoked by contextual processing in attentional orienting.

PubMed

Zhao, Shuo; Li, Chunlin; Uono, Shota; Yoshimura, Sayaka; Toichi, Motomi

2017-06-07

The ability to assess another person's direction of attention is paramount in social communication, many studies have reported a similar pattern between gaze and arrow cues in attention orienting. Neuroimaging research has also demonstrated no qualitative differences in attention to gaze and arrow cues. However, these studies were implemented under simple experiment conditions. Researchers have highlighted the importance of contextual processing (i.e., the semantic congruence between cue and target) in attentional orienting, showing that attentional orienting by social gaze or arrow cues could be modulated through contextual processing. Here, we examine the neural activity of attentional orienting by gaze and arrow cues in response to contextual processing using functional magnetic resonance imaging. The results demonstrated that the influence of neural activity through contextual processing to attentional orienting occurred under invalid conditions (when the cue and target were incongruent versus congruent) in the ventral frontoparietal network, although we did not identify any differences in the neural substrates of attentional orienting in contextual processing between gaze and arrow cues. These results support behavioural data of attentional orienting modulated by contextual processing based on the neurocognitive architecture.

Effects on micronuclei formation of 60-Hz electromagnetic field exposure with ionizing radiation, hydrogen peroxide, or c-Myc overexpression.

PubMed

Jin, Yeung Bae; Kang, Ga-Young; Lee, Jae Seon; Choi, Jong-Il; Lee, Ju-Woon; Hong, Seung-Cheol; Myung, Sung Ho; Lee, Yun-Sil

2012-04-01

Epidemiological studies have demonstrated a possible correlation between exposure to extremely low-frequency magnetic fields (ELF-MF) and cancer. However, this correlation has yet to be definitively confirmed by epidemiological studies. The principal objective of this study was to assess the effects of 60 Hz magnetic fields in a normal cell line system, and particularly in combination with various external factors, via micronucleus (MN) assays. Mouse embryonic fibroblast NIH3T3 cells and human lung fibroblast WI-38 cells were exposed for 4 h to a 60 Hz, 1 mT uniform magnetic field with or without ionizing radiation (IR, 2 Gy), H(2)O(2) (100 μM) and cellular myelocytomatosis oncogene (c-Myc) activation. The results obtained showed no significant differences between the cells exposed to ELF-MF alone and the unexposed cells. Moreover, no synergistic effects were observed when ELF-MF was combined with IR, H(2)O(2), and c-Myc activation. Our results demonstrate that ELF-MF did not enhance MN frequency by IR, H(2)O(2) and c-Myc activation.

Microfluidic rheology of active particle suspensions: Kinetic theory.

PubMed

Alonso-Matilla, Roberto; Ezhilan, Barath; Saintillan, David

2016-07-01

We analyze the effective rheology of a dilute suspension of self-propelled slender particles confined between two infinite parallel plates and subject to a pressure-driven flow. We use a continuum kinetic model to describe the configuration of the particles in the system, in which the disturbance flows induced by the swimmers are taken into account, and use it to calculate estimates of the suspension viscosity for a range of channel widths and flow strengths typical of microfluidic experiments. Our results are in agreement with previous bulk models, and in particular, demonstrate that the effect of activity is strongest at low flow rates, where pushers tend to decrease the suspension viscosity whereas pullers enhance it. In stronger flows, dissipative stresses overcome the effects of activity leading to increased viscosities followed by shear-thinning. The effects of confinement and number density are also analyzed, and our results confirm the apparent transition to superfluidity reported in recent experiments on pusher suspensions at intermediate densities. We also derive an approximate analytical expression for the effective viscosity in the limit of weak flows and wide channels, and demonstrate good agreement between theory and numerical calculations.

In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells.

PubMed

Sales, Natiely S; Silva, Jamile R; Aps, Luana R M M; Silva, Mariângela O; Porchia, Bruna F M M; Ferreira, Luís Carlos S; Diniz, Mariana O

2017-12-19

In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8 + T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8 + T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of moving spars for active aeroelastic structures

NASA Astrophysics Data System (ADS)

Amprikidis, Michael; Cooper, Jonathan E.

2003-08-01

This paper describes a research program investigating the development of "moving spars" to enable active aeroelastic control of aerospace structures. A number of different concepts have been considered as part of the EU funded Active Aeroelastic Aircraft Structures (3AS) project that enable the control of the bending and torsional stiffness of aircraft wings through changes in the internal aircraft structure. The aeroelastic behaviour, in particular static deflections, can be controlled as desired through changes in the position, orientation and stiffness of the spars. The concept described in this paper is based upon translational movement of the spars. This will result in changes in the torsional stiffness and shear centre position whilst leaving the bending stiffness unaffected. An analytical study of the aeroelastic behaviour demonstrates the benefits of using such an approach. An experimental investigation involving construction and bench testing of the concepts was undertaken to demonstrate its feasibility. Finally, a wind tunnel test of simple wing models constructed using these concepts was performed. The simulated and experimental results show that it is possible to control the wind twist in practice.

Visual Search Elicits the Electrophysiological Marker of Visual Working Memory

PubMed Central

Emrich, Stephen M.; Al-Aidroos, Naseem; Pratt, Jay; Ferber, Susanne

2009-01-01

Background Although limited in capacity, visual working memory (VWM) plays an important role in many aspects of visually-guided behavior. Recent experiments have demonstrated an electrophysiological marker of VWM encoding and maintenance, the contralateral delay activity (CDA), which has been shown in multiple tasks that have both explicit and implicit memory demands. Here, we investigate whether the CDA is evident during visual search, a thoroughly-researched task that is a hallmark of visual attention but has no explicit memory requirements. Methodology/Principal Findings The results demonstrate that the CDA is present during a lateralized search task, and that it is similar in amplitude to the CDA observed in a change-detection task, but peaks slightly later. The changes in CDA amplitude during search were strongly correlated with VWM capacity, as well as with search efficiency. These results were paralleled by behavioral findings showing a strong correlation between VWM capacity and search efficiency. Conclusions/Significance We conclude that the activity observed during visual search was generated by the same neural resources that subserve VWM, and that this activity reflects the maintenance of previously searched distractors. PMID:19956663

ERP Modulation during Observation of Abstract Paintings by Franz Kline

PubMed Central

Sbriscia-Fioretti, Beatrice; Berchio, Cristina; Freedberg, David; Gallese, Vittorio; Umiltà, Maria Alessandra

2013-01-01

The aim of this study was to test the involvement of sensorimotor cortical circuits during the beholding of the static consequences of hand gestures devoid of any meaning.In order to verify this hypothesis we performed an EEG experiment presenting to participants images of abstract works of art with marked traces of brushstrokes. The EEG data were analyzed by using Event Related Potentials (ERPs). We aimed to demonstrate a direct involvement of sensorimotor cortical circuits during the beholding of these selected works of abstract art. The stimuli consisted of three different abstract black and white paintings by Franz Kline. Results verified our experimental hypothesis showing the activation of premotor and motor cortical areas during stimuli observation. In addition, abstract works of art observation elicited the activation of reward-related orbitofrontal areas, and cognitive categorization-related prefrontal areas. The cortical sensorimotor activation is a fundamental neurophysiological demonstration of the direct involvement of the cortical motor system in perception of static meaningless images belonging to abstract art. These results support the role of embodied simulation of artist’s gestures in the perception of works of art. PMID:24130693

Active ester functional single core magnetic nanostructures as a versatile immobilization matrix for effective bioseparation and catalysis.

PubMed

Gelbrich, Thorsten; Reinartz, Michael; Schmidt, Annette M

2010-03-08

Multifunctional nanocarriers for amino functional targets with a high density of accessible binding sites are obtained in a single polymerization step by grafting from copolymerization of an active ester monomer from superparamagnetic cores. As a result of the brush-like structure of the highly dispersed shell, the nano-objects exhibit an available capture capacity for amines that is found to be up to 2 orders of magnitude higher than for commercial magnetic beads, and the functional brush shell can serve as a template for many types of pendant functional groups and molecules. As comonomer, oligo(ethylene glycol) methacrylate allows for excellent water solubility at room temperature, biocompatibility, and thermoflocculation. We demonstrate the biorelated applicability of the hybrid nanoparticles by two different approaches. In the first approach, the immobilization of trypsin to the core-shell nanoparticles results in highly active, nanoparticulate biocatalysts that can easily be separated magnetically. Second, we demonstrate that the obtained nanoparticles are suitable for the effective labeling of cell membranes, opening a novel pathway for the easy and effective isolation of membrane proteins.

Functional neuronal processing of body odors differs from that of similar common odors.

PubMed

Lundström, Johan N; Boyle, Julie A; Zatorre, Robert J; Jones-Gotman, Marilyn

2008-06-01

Visual and auditory stimuli of high social and ecological importance are processed in the brain by specialized neuronal networks. To date, this has not been demonstrated for olfactory stimuli. By means of positron emission tomography, we sought to elucidate the neuronal substrates behind body odor perception to answer the question of whether the central processing of body odors differs from perceptually similar nonbody odors. Body odors were processed by a network that was distinctly separate from common odors, indicating a separation in the processing of odors based on their source. Smelling a friend's body odor activated regions previously seen for familiar stimuli, whereas smelling a stranger activated amygdala and insular regions akin to what has previously been demonstrated for fearful stimuli. The results provide evidence that social olfactory stimuli of high ecological relevance are processed by specialized neuronal networks similar to what has previously been demonstrated for auditory and visual stimuli.

Oxide Semiconductor-Based Flexible Organic/Inorganic Hybrid Thin-Film Transistors Fabricated on Polydimethylsiloxane Elastomer.

PubMed

Jung, Soon-Won; Choi, Jeong-Seon; Park, Jung Ho; Koo, Jae Bon; Park, Chan Woo; Na, Bock Soon; Oh, Ji-Young; Lim, Sang Chul; Lee, Sang Seok; Chu, Hye Yong

2016-03-01

We demonstrate flexible organic/inorganic hybrid thin-film transistors (TFTs) on a polydimethysilox- ane (PDMS) elastomer substrate. The active channel and gate insulator of the hybrid TFT are composed of In-Ga-Zn-O (IGZO) and blends of poly(vinylidene fluoride-trifluoroethylene) [P(VDF- TrFE)] with poly(methyl methacrylate) (PMMA), respectively. It has been confirmed that the fabri- cated TFT display excellent characteristics: the recorded field-effect mobility, sub-threshold voltage swing, and I(on)/I(off) ratio were approximately 0.35 cm2 V(-1) s(-1), 1.5 V/decade, and 10(4), respectively. These characteristics did not experience any degradation at a bending radius of 15 mm. These results correspond to the first demonstration of a hybrid-type TFT using an organic gate insulator/oxide semiconducting active channel structure fabricated on PDMS elastomer, and demonstrate the feasibility of a promising device in a flexible electronic system.

Developing pharmacy student communication skills through role-playing and active learning.

PubMed

Luiz Adrian, Julie Ann; Zeszotarski, Paula; Ma, Carolyn

2015-04-25

To evaluate the impact on pharmacy students of a communication course, which used role-playing to develop active-learning skills. Students role-playing pharmacists in patient care scenarios were critiqued by students and pharmacist faculty members. Grading was performed using the rubric inspired by Bruce Berger's Communication Skills for Pharmacists. Written skills were evaluated using student written critique questionnaires. Students completed precourse and postcourse self-assessment surveys. Preceptor evaluations were analyzed for course impact. Students demonstrated improvement in oral skills based on role-play scores (45.87/50) after practice sessions. The average score based on the student questionnaire was 9.31/10. Gain was demonstrated in all defined course objectives. Impact on introductory pharmacy practice experience (IPPE) communication objectives was insignificant. Student evaluations for course and teaching strategy reflected a high average. Study results demonstrated improvement in oral and written communication skills that may help improve interprofessional teamwork between pharmacists and other health care providers.

Light generated bubble for microparticle propulsion.

PubMed

Frenkel, Ido; Niv, Avi

2017-06-06

Light activated motion of micron-sized particles with effective forces in the range of micro-Newtons is hereby proposed and demonstrated. Our investigation shows that this exceptional amount of force results from accumulation of light-generated heat by a micron-sized particle that translates into motion due to a phase transition in the nearby water. High-speed imagery indicates the role of bubble expansion and later collapse in this event. Comparing observations with known models reveals a dynamic behavior controlled by polytropic trapped vapor and the inertia of the surrounding liquid. The potential of the proposed approach is demonstrated by realization of disordered optical media with binary light-activated switching from opacity to high transparency.

Evaluation of anti-GERD activity of gastro retentive drug delivery system of itopride hydrochloride.

PubMed

Satapathy, Trilochan; Panda, Prasana K; Goyal, Amit K; Rath, Goutam

2010-08-01

The present work describes the formulation and evaluation of the gastroretentive system of Itopride hydrochloride. In this research, we have formulated floating hydrogel-based microspheres employing calcium carbonate (CaCO(3)) as a gas forming agent dispersed in alginate matrix. In vitro characterizations such as drug content, particle size, and drug release were carried out. GI motility was determined by administration of charcoal meal to rats. Results demonstrated that prepared microspheres were spherical in shape with smooth surface, good loading efficiency, and excellent buoyancy. The gastro retentive dosage form of itiopride demonstrated significant antacid, anti-ulcer, and anti-GERD activity after 12 hours in comparison with the conventional dosage form.

Long thoracic neuropathy from athletic activity.

PubMed

Schultz, J S; Leonard, J A

1992-01-01

Four cases of long thoracic mononeuropathy associated with sports participation are presented. Each patient developed shoulder pain or dysfunction after an acute event or vigorous activity, and demonstrated scapular winging consistent with serratus anterior weakness. The diagnosis was confirmed with electromyography in each case. It is suggested that the athletic activity caused a stretch injury to the long thoracic nerve. Conservative management, consisting of range of motion exercises for the shoulder and strengthening of the serratus anterior muscle, resulted in a favorable outcome in all patients.

Physics and chemistry of antimicrobial behavior of ion-exchanged silver in glass.

PubMed

Borrelli, N F; Senaratne, W; Wei, Y; Petzold, O

2015-02-04

The results of a comprehensive study involving the antimicrobial activity in a silver ion-exchanged glass are presented. The study includes the glass composition, the method of incorporating silver into the glass, the effective concentration of the silver available at the glass surface, and the effect of the ambient environment. A quantitative kinetic model that includes the above factors in predicting the antimicrobial activity is proposed. Finally, experimental data demonstrating antibacterial activity against Staphylococcus aureus with correlation to the predicted model is shown.

Support effects in catalysis studied by in-situ sum frequency generation vibrational spectroscopy and in-situ x-ray spectroscopies

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

Kennedy, Griffin John

Here, kinetic measurements are paired with in-situ spectroscopic characterization tools to investigate colloidally based, supported Pt catalytic model systems in order to elucidate the mechanisms by which metal and support work in tandem to dictate activity and selectivity. The results demonstrate oxide support materials, while inactive in absence of Pt nanoparticles, possess unique active sites for the selective conversion of gas phase molecules when paired with an active metal catalyst.

Giant Volume Change of Active Gels under Continuous Flow

DTIC Science & Technology

2014-04-21

harnessing chemical energy to produce motion, for example, using the energy released by ATP hydrolysis to power the directed movement of muscle fibers or micro ...microfluidic systems to generate capsules of biopolymer hydrogels, Herr demonstrated the use of gels for automated microfluidic protein blotting,13 Wu...active gels driven by the Belousov−Zhabotinsky reaction. These results demon- strate that microfluidics offers a useful and facile experimental

Comparison of the volatile emission profiles of ground almond and pistachio mummies: part 2 - critical changes in emission profiles as a result of increasing the water activity

USDA-ARS?s Scientific Manuscript database

In recent field trapping studies ground pistachio and almond mummies were reported to attract adult navel orangeworm moths, which showed a slight preference for the dry pistachio mummy matrix depending on the year evaluated. Recent work in these laboratories has demonstrated that the water activity ...

[Comparative study of the antimicrobial effect of various cavity liners used in conservative dentistry].

PubMed

Pumarola Suñé, J; Espias Gómez, A; Canalda Sahli, C

1989-01-01

We have compared the microbiological activity of the following cavity liners: Life, Dycal II, Calcipulpe, Pure calcium hydroxide and Cavitec; against five different bacterial strains: Veillonella parvula, Bacteroides fragilis, Peptococcus s.p., Staphylococcus aureus, and Streptococcus beta hemolytic: The results demonstrate the higher antimicrobial activity of the manufactured cavity liners with calcium hydroxide base in comparison with the pure calcium hydroxide.

CF6 Jet Engine Performance Improvement: High Pressure Turbine Active Clearance Control

NASA Technical Reports Server (NTRS)

Rich, S. E.; Fasching, W. A.

1982-01-01

An active clearance control system was developed which reduces fuel consumption and performance degradation. This system utilizes compressor discharge air during takeoff and fan discharge air during cruise to impinge on the shroud structure to improve the thermal response. The system was evaluated in component and engine tests. The test results demonstrated a performance improvement of 0.7 percent in cruise SFC.

The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase

PubMed Central

Cross, Janet V; Foss, Frank W; Rady, Joshua M; Macdonald, Timothy L; Templeton, Dennis J

2007-01-01

Background Dietary isothiocyanates (ITCs) are electrophilic compounds that have diverse biological activities including induction of apoptosis and effects on cell cycle. They protect against experimental carcinogenesis in animals, an activity believed to result from the transcriptional induction of "Phase 2" enzymes. The molecular mechanism of action of ITCs is unknown. Since ITCs are electrophiles capable of reacting with sulfhydryl groups on amino acids, we hypothesized that ITCs induce their biological effects through covalent modification of proteins, leading to changes in cell regulatory events. We previously demonstrated that stress-signaling kinase pathways are inhibited by other electrophilic compounds such as menadione. We therefore tested the effects of nutritional ITCs on MEKK1, an upstream regulator of the SAPK/JNK signal transduction pathway. Methods The activity of MEKK1 expressed in cells was monitored using in vitro kinase assays to measure changes in catalytic activity. The activity of endogenous MEKK1, immunopurified from ITC treated and untreated LnCAP cells was also measured by in vitro kinase assay. A novel labeling and affinity reagent for detection of protein modification by ITCs was synthesized and used in competition assays to monitor direct modification of MEKK1 by ITC. Finally, immunoblots with phospho-specific antibodies were used to measure the activity of MAPK protein kinases. Results ITCs inhibited the MEKK1 protein kinase in a manner dependent on a specific cysteine residue in the ATP binding pocket. Inhibition of MEKK1 catalytic activity was due to direct, covalent and irreversible modification of the MEKK1 protein itself. In addition, ITCs inhibited the catalytic activity of endogenous MEKK1. This correlated with inhibition of the downstream target of MEKK1 activity, i.e. the SAPK/JNK kinase. This inhibition was specific to SAPK, as parallel MAPK pathways were unaffected. Conclusion These results demonstrate that MEKK1 is directly modified and inhibited by ITCs, and that this correlates with inhibition of downstream activation of SAPK. These results support the conclusion that ITCs may carry out many of their actions by directly targeting important cell regulatory proteins. PMID:17894894

A prospective, observational study comparing the PK/PD relationships of generic Meropenem (Mercide®) to the innovator brand in critically ill patients

PubMed Central

Mer, Mervyn; Snyman, Jacques Rene; van Rensburg, Constance Elizabeth Jansen; van Tonder, Jacob John; Laurens, Ilze

2016-01-01

Introduction Clinicians’ skepticism, fueled by evidence of inferiority of some multisource generic antimicrobial products, results in the underutilization of more cost-effective generics, especially in critically ill patients. The aim of this observational study was to demonstrate equivalence between the generic or comparator brand of meropenem (Mercide®) and the leading innovator brand (Meronem®) by means of an ex vivo technique whereby antimicrobial activity is used to estimate plasma concentration of the active moiety. Methods Patients from different high care and intensive care units were recruited for observation when prescribed either of the meropenem brands under investigation. Blood samples were collected over 6 hours after a 30 minute infusion of the different brands. Meropenem concentration curves were established against United States Pharmacopeia standard meropenem (Sigma-Aldrich) by using standard laboratory techniques for culture of Klebsiella pneumoniae. Patients’ plasma samples were tested ex vivo, using a disc diffusion assay, to confirm antimicrobial activity and estimate plasma concentrations of the two brands. Results Both brands of meropenem demonstrated similar curves in donor plasma when concentrations in vials were confirmed. Patient-specific serum concentrations were determined from zones of inhibition against a standard laboratory Klebsiella strain ex vivo, confirming at least similar in vivo concentrations as the concentration curves (90% confidence interval) overlapped; however, the upper limit of the area under the curve for the ratio comparator/innovator exceeded the 1.25-point estimate, i.e., 4% higher for comparator meropenem. Conclusion This observational, in-practice study demonstrates similar ex vivo activity and in vivo plasma concentration time curves for the products under observation. Assay sensitivity is also confirmed. Current registration status of generic small molecules is in place. The products are therefore clinically interchangeable based on registration status as well as bioassay results, demonstrating sufficient overlap for clinical comfort. The slightly higher observed comparator meropenem concentration (4%) is still clinically acceptable due to the large therapeutic index and should ally fears of inferiority. PMID:27895516

[Phonological awareness improvement in primary school students].

PubMed

Cárnio, Maria Sílvia; dos Santos, Daniele

2005-01-01

Phonological awareness in primary school students. To verify the improvement of phonological awareness in primary school students after a speech and language stimulation program. 20 students with the worst results in the first literacy exam were selected. Phonological awareness tests were analyzed at the beginning and at the end of the stimulation program. Most of the subjects demonstrated to have a notion about phonological awareness activities. Students demonstrated improvement, suggesting the effectiveness of the program.

Antiviral Activity of Peanut (Arachis hypogaea L.) Skin Extract Against Human Influenza Viruses.

PubMed

Makau, Juliann Nzembi; Watanabe, Ken; Mohammed, Magdy M D; Nishida, Noriyuki

2018-05-30

The high propensity of influenza viruses to develop resistance to antiviral drugs necessitates the continuing search for new therapeutics. Peanut skins, which are low-value byproducts of the peanut industry, are known to contain high levels of polyphenols. In this study, we investigated the antiviral activity of ethanol extracts of peanut skins against various influenza viruses using cell-based assays. Extracts with a higher polyphenol content exhibited higher antiviral activities, suggesting that the active components are the polyphenols. An extract prepared from roasted peanut skins effectively inhibited the replication of influenza virus A/WSN/33 with a half maximal inhibitory concentration of 1.3 μg/mL. Plaque assay results suggested that the extract inhibits the early replication stages of the influenza virus. It demonstrated activity against both influenza type A and type B viruses. Notably, the extract exhibited a potent activity against a clinical isolate of the 2009 H1N1 pandemic, which had reduced sensitivity to oseltamivir. Moreover, a combination of peanut skin extract with the anti-influenza drugs, oseltamivir and amantadine, synergistically increased their antiviral activity. These data demonstrate the potential application of peanut skin extract in the development of new therapeutic options for influenza management.