Review of cyclotron production and quality control of ``High specific activity'' radionuclides for biomedical, biological, industrial and environmental applications at INFN-LASA

NASA Astrophysics Data System (ADS)

Birattari, C.; Bonardi, M.; Groppi, F.; Gini, L.

2001-12-01

At the "Radiochemistry Laboratory" of Accelerators and Applied Superconductivity Laboratory, LASA, a wide range of high specific activity radionuclides, RNs, have been produced in No Carrier Added form, for both basic research and application purposes. Use was made of the AVF proton cyclotron (K=45) of Milan University (up to 1987). More recently, the irradiations were carried out at the Scanditronix MC40 cyclotron (K=38; p, d, He-4 and He-3) of JRC-Ispra, Italy, of the European Community. In order to optimize the irradiation conditions for radioisotope production, a series of thin- and thick-target excitation functions have been experimentally determined. For each RN, a specific radiochemical separation has been developed in order to obtain GBq (mCi) amounts of the radiotracers in "high specific activity" No Carrier Added form (NCA).

High energy density supercapacitors from lignin derived submicron activated carbon fibers in aqueous electrolytes

NASA Astrophysics Data System (ADS)

Hu, Sixiao; Zhang, Sanliang; Pan, Ning; Hsieh, You-Lo

2014-12-01

Highly porous submicron activated carbon fibers (ACFs) were robustly generated from low sulfonated alkali lignin and fabricated into supercapacitors for capacitive energy storage. The hydrophilic and high specific surface ACFs exhibited large-size nanographites and good electrical conductivity to demonstrate outstanding electrochemical performance. ACFs from KOH activation, in particular, showed very high 344 F g-1 specific capacitance at low 1.8 mg cm-2 mass loading and 10 mV s-1 scan rate in aqueous electrolytes. Even at relatively high scan rate of 50 mV s-1 and mass loading of 10 mg cm-2, a decent specific capacitance of 196 F g-1 and a remarkable areal capacitance of 0.55 F cm-2 was obtained, leading to high energy density of 8.1 Wh kg-1 based on averaged electrodes mass. Furthermore, over 96% capacitance retention rates were achieved after 5000 charge/discharge cycles. Such excellent performance demonstrated great potential of lignin derived carbons for electrical energy storage.

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

PubMed

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

2017-01-01

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

Purification of charybdotoxine, a specific inhibitor of the high-conductance Ca/sup 2 +/-activated K/sup +/ channel

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

Smith, C.; Phillips, M.; Miller, C.

1986-11-05

Charybdotoxim is a high-affinity specific inhibitor of the high-conductance Ca/sup 2 +/-activated K/sup +/ channel found in the plasma membranes of many vertebrate cell types. Using Ca/sup 2 +/-activated K/sup +/ channels reconstituted into planar lipid bilayer membranes as an assay, the authors have purified the toxin from the venom of the scorpion Leiurus quinquestriatus by a two-step procedure involving chromatofocusing on SP-Sephadex, followed by reversed-phase high-performance liquid chromatography. Charybdotoxin is shown to be a highly basic protein with a mass of 10 kDa. Under the standard assay conditions, the purified toxin inhibits the Ca/sup 2 +/-activated K/sup +/ channelmore » with an apparent dissociation constant of 3.5 nM. The protein is unusually stable, with inhibitory potency being insensitive to boiling or exposure to organic solvents. The toxin's activity is sensitive to chymotrypsin treatment and to acylation of lysine groups. The protein may be radioiodinated without loss of activity.« less

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

PubMed

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

2013-07-01

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

Muscle Activation During ACL Injury Risk Movements in Young Female Athletes: A Narrative Review.

PubMed

Bencke, Jesper; Aagaard, Per; Zebis, Mette K

2018-01-01

Young, adolescent female athletes are at particular high risk of sustaining a non-contact anterior cruciate ligament (ACL) injury during sport. Through the last decades much attention has been directed toward various anatomical and biomechanical risk factors for non-contact ACL injury, and important information have been retrieved about the influence of external loading factors on ACL injury risk during given sports-specific movements. However, much less attention has been given to the aspect of neuromuscular control during such movements and only sparse knowledge exists on the specific muscle activation patterns involved during specific risk conditions. Therefore, the aim of this narrative review was (1) to describe anatomical aspects, strength aspects and biomechanical aspects relevant for the understanding of ACL non-contact injury mechanisms in young female athletes, and (2) to review the existing literature on lower limb muscle activation in relation to risk of non-contact ACL-injury and prevention of ACL injury in young female athletes. Studies investigating muscle activity patterns associated with sports-specific risk situations were identified, comprising cohort studies, intervention studies and prospective studies. Based on the retrieved studies, clear gender-specific differences in muscle activation and coordination were identified demonstrating elevated quadriceps activity and reduced hamstring activity in young female athletes compared to their male counterparts, and suggesting young female athletes to be at elevated risk of non-contact ACL injury. Only few studies ( n = 6) examined the effect of preventive exercise-based intervention protocols on lower limb muscle activation during sports-specific movements. A general trend toward enhanced hamstring activation was observed during selected injury risk situations (e.g., sidecutting and drop landings). Only a single study examined the association between muscle activation deficits and ACL injury risk, reporting that low medial hamstring activation and high vastus lateralis activation prior to landing was associated with an elevated incidence of ACL-injury. A majority of studies were performed in adult female athletes. The striking paucity of studies in adolescent female athletes emphasizes the need for increased research activities to examine of lower limb muscle activity in relation to non-contact ACL injury in this high-risk athlete population.

Method for preparing high specific activity 177Lu

DOEpatents

Mirzadeh, Saed; Du, Miting; Beets, Arnold L.; Knapp, Jr., Furn F.

2004-04-06

A method of separating lutetium from a solution containing Lu and Yb, particularly reactor-produced .sup.177 Lu and .sup.177 Yb, includes the steps of: providing a chromatographic separation apparatus containing LN resin; loading the apparatus with a solution containing Lu and Yb; and eluting the apparatus to chromatographically separate the Lu and the Yb in order to produce high-specific-activity .sup.177 Yb.

Preparation of highly porous binderless activated carbon electrodes from fibres of oil palm empty fruit bunches for application in supercapacitors.

PubMed

Farma, R; Deraman, M; Awitdrus, A; Talib, I A; Taer, E; Basri, N H; Manjunatha, J G; Ishak, M M; Dollah, B N M; Hashmi, S A

2013-03-01

Fibres from oil palm empty fruit bunches, generated in large quantities by palm oil mills, were processed into self-adhesive carbon grains (SACG). Untreated and KOH-treated SACG were converted without binder into green monolith prior to N2-carbonisation and CO2-activation to produce highly porous binderless carbon monolith electrodes for supercapacitor applications. Characterisation of the pore structure of the electrodes revealed a significant advantage from combining the chemical and physical activation processes. The electrochemical measurements of the supercapacitor cells fabricated using these electrodes, using cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge-discharge techniques consistently found that approximately 3h of activation time, achieved via a multi-step heating profile, produced electrodes with a high surface area of 1704m(2)g(-1) and a total pore volume of 0.889cm(3)g(-1), corresponding to high values for the specific capacitance, specific energy and specific power of 150Fg(-1), 4.297Whkg(-1) and 173Wkg(-1), respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Controlling protein release using biodegradable microparticles

NASA Astrophysics Data System (ADS)

Kline, Benjamin Patrick

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

A diet high in fat stimulates adipocyte proliferation in older (22 month) rats.

PubMed

Ellis, J R; McDonald, R B; Stern, J S

1990-01-01

The effect of a high fat diet in stimulating adipocyte proliferation, as measured by the incorporation of [3H]-thymidine into fat cell DNA, was studied in 22-month-old female Sprague-Dawley rats. Rats were fed a low fat (n = 10) or a high fat diet (n = 9) for a total of six days. On days 4 and 5 of dietary manipulation, rats were injected with 80 microCi/100 g body weight of [3H]-thymidine. Rats were continued on their respective diets for one more day, starved for 72 h and then refed a stock diet for three weeks in order to increase turnover of stroma cells, thus diluting the specific activity of stromal DNA with minimal effect on specific activity of fat cell DNA. The diet groups did not differ significantly with respect to body masses, food intake, parametrial (PARA) and retroperitoneal (RP) depot masses, cell number or cell size. The specific activity of DNA in both PARA and RP depots was greater in the adipocyte than in the stromavascular fraction. Specific activity of fat cells was significantly greater from rats fed the high fat than the low fat diet in both PARA and RP depots. Radioautography of adipose tissue confirmed that there was a greater percentage of adipocyte nuclei labeled in the rats fed the high fat diet. Also, there were few labeled nuclei found in stroma cells. In conclusion, older female rats increased adipocyte proliferation when fed a high fat diet.

Chemistry and radiochemistry of As, Re and Rh isotopes relevant to radiopharmaceutical applications: high specific activity radionuclides for imaging and treatment.

PubMed

Feng, Yutian; Phelps, Tim E; Carroll, Valerie; Gallazzi, Fabio; Sieckman, Gary; Hoffman, Timothy J; Barnes, Charles L; Ketring, Alan R; Hennkens, Heather M; Jurisson, Silvia S

2017-10-31

The chemistry and radiochemistry of high specific activity radioisotopes of arsenic, rhenium and rhodium are reviewed with emphasis on University of Missouri activities over the past several decades, and includes recent results. The nuclear facilities at the University of Missouri (10 MW research reactor and 16.5 MeV GE PETtrace cyclotron) allow research and development into novel theranostic radionuclides. The production, separation, enriched target recovery, radiochemistry, and chelation chemistry of 72,77 As, 186,188 Re and 105 Rh are discussed.

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

PubMed

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

2011-08-02

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

Marine Invertebrate Xenobiotic-Activated Nuclear Receptors: Their Application as Sensor Elements in High-Throughput Bioassays for Marine Bioactive Compounds

PubMed Central

Richter, Ingrid; Fidler, Andrew E.

2014-01-01

Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors are particularly well-suited to act as sensors in such bioassays. More specifically, xenobiotic-activated nuclear receptors (XANRs) regulate transcription of genes involved in xenobiotic detoxification. XANR ligand-binding domains (LBDs) may adaptively evolve to bind those bioactive, and potentially toxic, compounds to which organisms are normally exposed to through their specific diets. A brief overview of the function and taxonomic distribution of both vertebrate and invertebrate XANRs is first provided. Proof-of-concept experiments are then described which confirm that a filter-feeding marine invertebrate XANR LBD is activated by marine bioactive compounds. We speculate that increasing access to marine invertebrate genome sequence data, in combination with the expression of functional recombinant marine invertebrate XANR LBDs, will facilitate the generation of high-throughput bioassays/biosensors of widely differing specificities, but all based on activation of XANR LBDs. Such assays may find application in screening marine extracts for bioactive compounds that could act as drug lead compounds. PMID:25421319

Predictors of participation in sports after hip and knee arthroplasty.

PubMed

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

2012-02-01

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

Evaluation of Streptococcus pneumoniae Type XIV Opsonins by Phagocytosis-Associated Chemiluminescence and a Bactericidal Assay

PubMed Central

Gardner, Susan E.; Anderson, Donald C.; Webb, Bette J.; Stitzel, Ann E.; Edwards, Morven S.; Spitzer, Roger E.; Baker, Carol J.

1982-01-01

The relative roles of serum factors required for opsonization of type XIV Streptococcus pneumoniae were investigated by means of luminol-enhanced chemiluminescence (CL), bactericidal, and immunofluorescence assays employing adult sera containing high (>1,000 ng of antibody nitrogen per ml) or low (<200 ng of antibody nitrogen per ml) antibody concentrations as determined by radioimmunoassay. Specific antibody concentration correlated directly with both total and heat-labile CL activity (P < 0.005) and with the bactericidal index (P < 0.05) at a serum concentration of 10%. The importance of specific antibody as an opsonin was confirmed by the abolition of CL activity and immunoglobulin immunofluorescence observed after absorption of heated sera with type XIV pneumococcal cells and by the dose response in CL and bactericidal activity observed with the addition of immunoglobulin G to hypogammaglobulinemic serum. A role for the classical complement pathway in opsonization was indicated by significantly greater CL integrals for high-antibody sera than for low-antibody sera depleted of factor D and by the bactericidal activity noted for untreated, but not magnesium ethylene glycol-bis(β-aminoethyl ether)-N,N-tetraacetic acid-chelated low-antibody sera. The alternative pathway contributed more than half of the CL activity of both high- and low-antibody sera. However, after magnesium ethylene glycol-bis(β-aminoethyl ether)-N,N-tetraacetic acid chelation, only sera with high antibody concentrations or agammaglobulinemic serum reconstituted with immunoglobulin G with high specific antibody levels supported significant bactericidal activity. Therefore, type-specific antibody and complement promote opsonization of type XIV S. pneumoniae, and this may occur via either complement pathway. These results suggest that CL is a suitable tool to delineate serum factors and their contribution to opsonization, but results must be related to other functional assays. PMID:6802760

Decoupling the Effects of High Crystallinity and Surface Area on the Photocatalytic Overall Water Splitting over β-Ga2 O3 Nanoparticles by Chemical Vapor Synthesis.

PubMed

Lukic, Sasa; Menze, Jasper; Weide, Philipp; Busser, G Wilma; Winterer, Markus; Muhler, Martin

2017-09-11

Chemical vapor synthesis (CVS) is a unique method to prepare well-defined photocatalyst materials with both large specific surface area and a high degree of crystallinity. The obtained β-Ga 2 O 3 nanoparticles were optimized for photocatalysis by reductive photodeposition of the Rh/CrO x co-catalyst system. The influence of the degree of crystallinity and the specific surface area on photocatalytic aqueous methanol reforming and overall water splitting (OWS) was investigated by synthesizing β-Ga 2 O 3 samples in the temperature range from 1000 °C to 1500 °C. With increasing temperature, the specific surface area and the microstrain were found to decrease, whereas the degree of crystallinity and the crystallite size increased. Whereas the photocatalyst with the highest specific surface area showed the highest aqueous methanol reforming activity, the highest OWS activity was that for the sample with an optimum ratio between high degree of crystallinity and specific surface area. Thus, it was possible to show that the facile aqueous methanol reforming and the demanding OWS have different requirements for high photocatalytic activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immune Centroids Over-Sampling Method for Multi-Class Classification

DTIC Science & Technology

2015-05-22

recognize to specific antigens . The response of a receptor to an antigen can activate its hosting B-cell. Activated B-cell then proliferates and...modifying N.K. Jerne’s theory. The theory states that in a pre-existing group of lympho- cytes ( specifically B cells), a specific antigen only...the clusters of each small class, which have high data density, called global immune centroids over-sampling (denoted as Global-IC). Specifically

Unique processing during a period of high excitation/inhibition balance in adult-born neurons.

PubMed

Marín-Burgin, Antonia; Mongiat, Lucas A; Pardi, M Belén; Schinder, Alejandro F

2012-03-09

The adult dentate gyrus generates new granule cells (GCs) that develop over several weeks and integrate into the preexisting network. Although adult hippocampal neurogenesis has been implicated in learning and memory, the specific role of new GCs remains unclear. We examined whether immature adult-born neurons contribute to information encoding. By combining calcium imaging and electrophysiology in acute slices, we found that weak afferent activity recruits few mature GCs while activating a substantial proportion of the immature neurons. These different activation thresholds are dictated by an enhanced excitation/inhibition balance transiently expressed in immature GCs. Immature GCs exhibit low input specificity that switches with time toward a highly specific responsiveness. Therefore, activity patterns entering the dentate gyrus can undergo differential decoding by a heterogeneous population of GCs originated at different times.

14C content in vegetation in the vicinities of Brazilian nuclear power reactors.

PubMed

Dias, Cíntia Melazo; Santos, Roberto Ventura; Stenström, Kristina; Nícoli, Iêda Gomes; Skog, Göran; da Silveira Corrêa, Rosangela

2008-07-01

(14)C specific activities were measured in grass samples collected around Brazilian nuclear power reactors. The specific activity values varied between 227 and 299 Bq/kg C. Except for two samples which showed (14)C specific activities 22% above background values, half of the samples showed background specific activities, and the other half had a (14)C excess of 1-18%. The highest specific activities were found close to the nuclear power plants and along the main wind directions (NE and NNE). The activity values were found to decrease with increasing distance from the reactors. The unexpectedly high (14)C excess values found in two samples were related to the local topography, which favors (14)C accumulation and limits the dispersion of the plume. The results indicate a clear (14)C anthropogenic signal within 5 km around the nuclear power plants which is most prominent along northeastwards, the prevailing wind direction.

Method of preparing high specific activity platinum-195m

DOEpatents

Mirzadeh, Saed; Du, Miting; Beets, Arnold L.; Knapp, Jr., Furn F.

2004-06-15

A method of preparing high-specific-activity .sup.195m Pt includes the steps of: exposing .sup.193 Ir to a flux of neutrons sufficient to convert a portion of the .sup.193 Ir to .sup.195m Pt to form an irradiated material; dissolving the irradiated material to form an intermediate solution comprising Ir and Pt; and separating the Pt from the Ir by cation exchange chromatography to produce .sup.195m Pt.

Accelerator Production and Separations for High Specific Activity Rhenium-186

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

Jurisson, Silvia S.; Wilbur, D. Scott

2016-04-01

Tungsten and osmium targets were evaluated for the production of high specific activity rhenium-186. Rhenium-186 has potential applications in radiotherapy for the treatment of a variety of diseases, including targeting with monoclonal antibodies and peptides. Methods were evaluated using tungsten metal, tungsten dioxide, tungsten disulfide and osmium disulfide. Separation of the rhenium-186 produced and recycling of the enriched tungsten-186 and osmium-189 enriched targets were developed.

Self-diagnosis of active head lice infestation by individuals from an impoverished community: high sensitivity and specificity.

PubMed

Pilger, Daniel; Khakban, Adak; Heukelbach, Jorg; Feldmeier, Hermann

2008-01-01

To compare sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-diagnosis for head lice infestation with visual inspection, we conducted a study in an urban slum in Brazil. Individuals were asked about active head lice infestation (self-diagnosis); we performed visual inspection and thereafter wet combing (gold standard). Of the 175 individuals included, 77 (44%) had an active head lice infestation. For self-diagnosis, sensitivity (80.5%), specificity (91.8%), PPV (88.6%) and NPV (85.7%) were high. Sensitivity of visual inspection was 35.1%. Public health professionals can use self-diagnosis as a diagnostic tool, to estimate accurately prevalence of pediculosis in a community, and to monitor ongoing intervention strategies.

Comprehensive Interrogation of Natural TALE DNA Binding Modules and Transcriptional Repressor Domains

PubMed Central

Cong, Le; Zhou, Ruhong; Kuo, Yu-chi; Cunniff, Margaret; Zhang, Feng

2012-01-01

Transcription activator-like effectors (TALE) are sequence-specific DNA binding proteins that harbor modular, repetitive DNA binding domains. TALEs have enabled the creation of customizable designer transcriptional factors and sequence-specific nucleases for genome engineering. Here we report two improvements of the TALE toolbox for achieving efficient activation and repression of endogenous gene expression in mammalian cells. We show that the naturally occurring repeat variable diresidue (RVD) Asn-His (NH) has high biological activity and specificity for guanine, a highly prevalent base in mammalian genomes. We also report an effective TALE transcriptional repressor architecture for targeted inhibition of transcription in mammalian cells. These findings will improve the precision and effectiveness of genome engineering that can be achieved using TALEs. PMID:22828628

Highly conductive and porous activated reduced graphene oxide films for high-power supercapacitors.

PubMed

Zhang, Li Li; Zhao, Xin; Stoller, Meryl D; Zhu, Yanwu; Ji, Hengxing; Murali, Shanthi; Wu, Yaping; Perales, Stephen; Clevenger, Brandon; Ruoff, Rodney S

2012-04-11

We present a novel method to prepare highly conductive, free-standing, and flexible porous carbon thin films by chemical activation of reduced graphene oxide paper. These flexible carbon thin films possess a very high specific surface area of 2400 m(2) g(-1) with a high in-plane electrical conductivity of 5880 S m(-1). This is the highest specific surface area for a free-standing carbon film reported to date. A two-electrode supercapacitor using these carbon films as electrodes demonstrated an excellent high-frequency response, an extremely low equivalent series resistance on the order of 0.1 ohm, and a high-power delivery of about 500 kW kg(-1). While higher frequency and power values for graphene materials have been reported, these are the highest values achieved while simultaneously maintaining excellent specific capacitances and energy densities of 120 F g(-1) and 26 W h kg(-1), respectively. In addition, these free-standing thin films provide a route to simplify the electrode-manufacturing process by eliminating conducting additives and binders. The synthetic process is also compatible with existing industrial level KOH activation processes and roll-to-roll thin-film fabrication technologies. © 2012 American Chemical Society

Light-Activated Staudinger–Bertozzi Ligation within Living Animals

PubMed Central

Shah, Lisa; Laughlin, Scott T.; Carrico, Isaac S.

2016-01-01

The ability to regulate small molecule chemistry in vivo will enable new avenues of exploration in imaging and pharmacology. However, realization of these goals will require reactions with high specificity and precise control. Here we demonstrate photocontrol over the highly specific Staudinger–Bertozzi ligation in vitro and in vivo. Our simple approach, photocaging the key phosphine atom, allows for the facile production of reagents with photochemistry that can be engineered for specific applications. The resulting compounds, which are both stable and efficiently activated, enable the spatial labeling of metabolically introduced azides in vitro and on live zebrafish. PMID:27010217

Erythrocyte glucose-6-phosphate dehydrogenase from Brazilian opossum Didelphis marsupialis.

PubMed

Barretto, O C de O; Oshiro, M; Oliveira, R A G; Fedullo, J D L; Nonoyama, K

2006-05-01

In a comparative study of erythrocyte metabolism of vertebrates, the specific activity of glucose-6-phosphate dehydrogenase (G6PD) of the Brazilian opossum Didelphis marsupialis in a hemolysate was shown to be high, 207 +/- 38 IU g-1 Hb-1 min-1 at 37 degrees C, compared to the human erythrocyte activity of 12 +/- 2 IU g-1 Hb-1 min-1 at 37 degrees C. The apparent high specific activity of the mixture led us to investigate the physicochemical properties of the opossum enzyme. We report that reduced glutathione (GSH) in the erythrocytes was only 50% higher than in human erythrocytes, a value lower than expected from the high G6PD activity since GSH is maintained in a reduced state by G6PD activity. The molecular mass, determined by G-200 Sephadex column chromatography at pH 8.0, was 265 kDa, which is essentially the same as that of human G6PD (260 kDa). The Michaelis-Menten constants (Km: 55 microM) for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (Km: 3.3 microM) were similar to those of the human enzyme (Km: 50-70 and Km: 2.9-4.4, respectively). A 450-fold purification of the opossum enzyme was achieved and the specific activity of the purified enzyme, 90 IU/mg protein, was actually lower than the 150 IU/mg protein observed for human G6PD. We conclude that G6PD after purification from the hemolysate of D. marsupialis does not have a high specific activity. Thus, it is quite probable that the red cell hyperactivity reported may be explained by increased synthesis of G6PD molecules per unit of hemoglobin or to reduced inactivation in the RBC hemolysate.

Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection

PubMed Central

Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry AF; Rothman, Alan L; Mathew, Anuja

2014-01-01

Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS126–34-specific CD8+ T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS126–34-specific and other DENV epitope-specific CD8+ T cells, as well as total CD8+ T cells, expressed an activated phenotype (CD69+ and/or CD38+) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8+ T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. PMID:23941420

Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

PubMed

Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

2014-01-01

Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. © 2013 John Wiley & Sons Ltd.

Effects of CO{sub 2} activation on electrochemical performance of microporous carbons derived from poly(vinylidene fluoride)

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

Lee, Seul-Yi; Park, Soo-Jin, E-mail: sjpark@inha.ac.kr

In this work, we have prepared microporous carbons (MPCs) derived from poly(vinylidene fluoride) (PVDF), and the physical activation of MPCs using CO{sub 2} gas is subsequently carried out with various activation temperatures to investigate the electrochemical performance. PVDF is successfully converted into MPCs with a high specific surface area and well-developed micropores. After CO{sub 2} activation, the specific surface areas of MPCs (CA-MPCs) are enhanced by 12% compared with non-activated MPCs. With increasing activation temperature, the micropore size distributions of A-MPCs also become narrower and shift to larger pore size. It is also confirmed that the CO{sub 2} activation hadmore » developed the micropores and introduced the oxygen-containing groups to MPCs′ surfaces. From the results, the specific capacitances of the electrodes in electric double layer capacitors (EDLCs) based on CA-MPCs are distinctly improved through CO{sub 2} activation. The highest specific capacitance of the A-MPCs activated at 700 °C is about 125 F/g, an enhancement of 74% in comparison with NA-MPCs, at a discharge current of 2 A/g in a 6 M KOH electrolyte solution. We also found that micropore size of 0.67 nm has a specific impact on the capacitance behaviors, besides the specific surface area of the electrode samples. - Graphical abstract: The A-MPC samples with high specific surface area (ranging from 1030 to 1082 m{sup 2}/g), corresponding to micropore sizes of 0.67 and 0.72 nm, and with the amount of oxygen-containing groups ranging from 3.2% to 4.4% have been evaluated as electrodes for EDLC applications. . Display Omitted - Highlights: • Microporous carbons (MPCs) were synthesized without activation process. • Next, we carried out the CO{sub 2} activation of MPCs with activation temperatures. • It had developed the micropores and introduced the O-functional groups to MPCs. • The highest specific capacitance: 125 F/g, an increase of 74% compared to MPCs.« less

The effect on some enzymes of rat tissue of diets low in fat content.

PubMed

Bartley, W; Dean, B; Taylor, C B; Bailey, E

1967-05-01

1. Rats of two strains were kept on three different diets; one was a commercial diet of rat pellets, one contained about 80% of sucrose and 20% of casein and was supplemented with corn oil, and the third was a similar diet without the corn oil. 2. On the commercial diet, the specific activities of pyruvate kinase, glucose 6-phosphate dehydrogenase and fructose 1,6-diphosphatase in the livers of one strain of rats (strain A) were 1.5-3 times those in the other strain (strain B). When the diet high in sucrose and supplemented with corn oil was given, there were large increases in the specific activity of pyruvate kinase, glucose 6-phosphate dehydrogenase and fructose 1,6-diphosphatase in the livers of strain A rats. With strain B rats the increases were much smaller. Omission of corn oil from the diet caused a threefold increase in the specific activity of glucose 6-phosphate dehydrogenase in strain B rats, but had little effect on other enzymes. 3. The enzymes of the kidneys and hearts of strain A rats were also more active than those of strain B rats. In strain A rats, the specific activities of pyruvate kinase and fructose 1,6-diphosphatase in the kidney increased when the sucrose content of the diet was high, but in the kidneys of strain B rats there was little change. 4. In strain A rats, the specific activity of pyruvate kinase in the heart more than doubled with the high-sucrose-corn oil diet and increased threefold when corn oil was omitted. No changes were seen in strain B rats. 5. In strain A rats, omission of corn oil from the diet increased the ability of the kidneys to synthesize glucose from lactate. 6. In strain B rats, addition of corn oil to the diet resulted in a decrease in the liver in the specific activity of ATP citrate lyase and in the ability to incorporate acetate into lipid.

Exceptional oxygen reduction reaction activity and durability of platinum–nickel nanowires through synthesis and post-treatment optimization

DOE PAGES

Alia, Shaun M.; Ngo, Chilan; Shulda, Sarah; ...

2017-04-11

For the first time, extended nanostructured catalysts are demonstrated with both high specific activity (>6000 μA cm Pt –2 at 0.9 V) and high surface areas (>90 m 2 g Pt –1). Platinum–nickel (Pt—Ni) nanowires, synthesized by galvanic displacement, have previously produced surface areas in excess of 90 m 2 g Pt –1, a significant breakthrough in and of itself for extended surface catalysts. Unfortunately, these materials were limited in terms of their specific activity and durability upon exposure to relevant electrochemical test conditions. Through a series of optimized postsynthesis steps, significant improvements were made to the activity (3-fold increasemore » in specific activity), durability (21% mass activity loss reduced to 3%), and Ni leaching (reduced from 7 to 0.3%) of the Pt—Ni nanowires. Finally, these materials show more than a 10-fold improvement in mass activity compared to that of traditional carbon-supported Pt nanoparticle catalysts and offer significant promise as a new class of electrocatalysts in fuel cell applications.« less

Exceptional oxygen reduction reaction activity and durability of platinum–nickel nanowires through synthesis and post-treatment optimization

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

Alia, Shaun M.; Ngo, Chilan; Shulda, Sarah

For the first time, extended nanostructured catalysts are demonstrated with both high specific activity (>6000 μA cm Pt –2 at 0.9 V) and high surface areas (>90 m 2 g Pt –1). Platinum–nickel (Pt—Ni) nanowires, synthesized by galvanic displacement, have previously produced surface areas in excess of 90 m 2 g Pt –1, a significant breakthrough in and of itself for extended surface catalysts. Unfortunately, these materials were limited in terms of their specific activity and durability upon exposure to relevant electrochemical test conditions. Through a series of optimized postsynthesis steps, significant improvements were made to the activity (3-fold increasemore » in specific activity), durability (21% mass activity loss reduced to 3%), and Ni leaching (reduced from 7 to 0.3%) of the Pt—Ni nanowires. Finally, these materials show more than a 10-fold improvement in mass activity compared to that of traditional carbon-supported Pt nanoparticle catalysts and offer significant promise as a new class of electrocatalysts in fuel cell applications.« less

Salivary aldehyde dehydrogenase - temporal and population variability, correlations with drinking and smoking habits and activity towards aldehydes contained in food.

PubMed

Giebułtowicz, Joanna; Dziadek, Marta; Wroczyński, Piotr; Woźnicka, Katarzyna; Wojno, Barbara; Pietrzak, Monika; Wierzchowski, Jacek

2010-01-01

Fluorimetric method based on oxidation of the fluorogenic 6-methoxy-2-naphthaldehyde was applied to evaluate temporal and population variability of the specific activity of salivary aldehyde dehydrogenase (ALDH) and the degree of its inactivation in healthy human population. Analyzed was also its dependence on drinking and smoking habits, coffee consumption, and its sensitivity to N-acetylcysteine. Both the specific activity of salivary ALDH and the degree of its inactivation were highly variable during the day, with the highest activities recorded in the morning hours. The activities were also highly variable both intra- and interpersonally, and negatively correlated with age, and this correlation was stronger for the subgroup of volunteers declaring abstinence from alcohol and tobacco. Moderately positive correlations of salivary ALDH specific activity with alcohol consumption and tobacco smoking were also recorded (r(s) ~0.27; p=0.004 and r(s) =0.30; p=0.001, respectively). Moderate coffee consumption correlated positively with the inactivation of salivary ALDH, particularly in the subgroup of non-drinking and non-smoking volunteers. It was found that mechanical stimulation of the saliva flow increases the specific activity of salivary ALDH. The specific activity of the salivary ALDH was strongly and positively correlated with that of superoxide dismutase, and somewhat less with salivary peroxidase. The antioxidant-containing drug N-acetylcysteine increased activity of salivary ALDH presumably by preventing its inactivation in the oral cavity. Some food-related aldehydes, mainly cinnamic aldehyde and anisaldehyde, were excellent substrates of the salivary ALDH3A1 enzyme, while alkenals, particularly those with short chain, were characterized by lower affinity towards this enzyme but high catalytic constants. The protective role of salivary ALDH against aldehydes in food and those found in the cigarette smoke is discussed, as well as its participation in diminishing the effects of alcohol- and smoking-related oxidative stress.

A biosensor generated via high throughput screening quantifies cell edge Src dynamics

PubMed Central

Gulyani, Akash; Vitriol, Eric; Allen, Richard; Wu, Jianrong; Gremyachinskiy, Dmitriy; Lewis, Steven; Dewar, Brian; Graves, Lee M.; Kay, Brian K.; Kuhlman, Brian; Elston, Tim; Hahn, Klaus M.

2011-01-01

Fluorescent biosensors for living cells currently require laborious optimization and a unique design for each target. They are limited by the availability of naturally occurring ligands with appropriate target specificity. Here we describe a biosensor based on an engineered fibronectin monobody scaffold that can be tailored to bind different targets via high throughput screening. This Src family kinase (SFK) biosensor was made by derivatizing a monobody specific for activated SFK with a bright dye whose fluorescence increases upon target binding. We identified sites for dye attachment and alterations to eliminate vesiculation in living cells, providing a generalizable scaffold for biosensor production. This approach minimizes cell perturbation because it senses endogenous, unmodified target, and because sensitivity is enhanced by direct dye excitation. Automated correlation of cell velocities and SFK activity revealed that SFK are activated specifically during protrusion. Activity correlates with velocity, and peaks 1–2 microns from the leading edge. PMID:21666688

Thermal Technology Development Activities at the Goddard Space Flight Center - 2001

NASA Technical Reports Server (NTRS)

Butler, Dan

2002-01-01

This presentation provides an overview of thermal technology development activities carried out at NASA's Goddard Space Flight Center during 2001. Specific topics covered include: two-phase systems (heat pipes, capillary pumped loops, vapor compression systems and phase change materials), variable emittance systems, advanced coatings, high conductivity materials and electrohydrodynamic (EHD) thermal coatings. The application of these activities to specific space missions is also discussed.

Design of aqueous redox-enhanced electrochemical capacitors with high specific energies and slow self-discharge.

PubMed

Chun, Sang-Eun; Evanko, Brian; Wang, Xingfeng; Vonlanthen, David; Ji, Xiulei; Stucky, Galen D; Boettcher, Shannon W

2015-08-04

Electrochemical double-layer capacitors exhibit high power and long cycle life but have low specific energy compared with batteries, limiting applications. Redox-enhanced capacitors increase specific energy by using redox-active electrolytes that are oxidized at the positive electrode and reduced at the negative electrode during charging. Here we report characteristics of several redox electrolytes to illustrate operational/self-discharge mechanisms and the design rules for high performance. We discover a methyl viologen (MV)/bromide electrolyte that delivers a high specific energy of ∼14 Wh kg(-1) based on the mass of electrodes and electrolyte, without the use of an ion-selective membrane separator. Substituting heptyl viologen for MV increases stability, with no degradation over 20,000 cycles. Self-discharge is low, due to adsorption of the redox couples in the charged state to the activated carbon, and comparable to cells with inert electrolyte. An electrochemical model reproduces experiments and predicts that 30-50 Wh kg(-1) is possible with optimization.

Design of aqueous redox-enhanced electrochemical capacitors with high specific energies and slow self-discharge

PubMed Central

Chun, Sang-Eun; Evanko, Brian; Wang, Xingfeng; Vonlanthen, David; Ji, Xiulei; Stucky, Galen D.; Boettcher, Shannon W.

2015-01-01

Electrochemical double-layer capacitors exhibit high power and long cycle life but have low specific energy compared with batteries, limiting applications. Redox-enhanced capacitors increase specific energy by using redox-active electrolytes that are oxidized at the positive electrode and reduced at the negative electrode during charging. Here we report characteristics of several redox electrolytes to illustrate operational/self-discharge mechanisms and the design rules for high performance. We discover a methyl viologen (MV)/bromide electrolyte that delivers a high specific energy of ∼14 Wh kg−1 based on the mass of electrodes and electrolyte, without the use of an ion-selective membrane separator. Substituting heptyl viologen for MV increases stability, with no degradation over 20,000 cycles. Self-discharge is low, due to adsorption of the redox couples in the charged state to the activated carbon, and comparable to cells with inert electrolyte. An electrochemical model reproduces experiments and predicts that 30–50 Wh kg−1 is possible with optimization. PMID:26239891

Recyclable Thermoresponsive Polymer-β-Glucosidase Conjugate with Intact Hydrolysis Activity.

PubMed

Mukherjee, Ishita; Sinha, Sushant K; Datta, Supratim; De, Priyadarsi

2018-06-11

β-Glucosidase (BG) catalyzes the hydrolysis of cellobiose to glucose and is a rate-limiting enzyme in the conversion of lignocellulosic biomass to sugars toward biofuels. Since the cost of enzyme is a major contributor to biofuel economics, we report the bioconjugation of a temperature-responsive polymer with the highly active thermophilic β-glucosidase (B8CYA8) from Halothermothrix orenii toward improving enzyme recyclability. The bioconjugate, with a lower critical solution temperature (LCST) of 33 °C withstands high temperatures up to 70 °C. Though the secondary structure of the enzyme in the conjugate is slightly distorted with a higher percentage of β-sheet like structure, the stability and specific activity of B8CYA8 in the conjugate remains unaltered up to 30 °C and retains more than 70% specific activity of the unmodified enzyme at 70 °C. The conjugate can be reused for β-glucosidic bond cleavage of cellobiose for at least four cycles without any significant loss in specific activity.

Porous silicon structures with high surface area/specific pore size

DOEpatents

Northrup, M.A.; Yu, C.M.; Raley, N.F.

1999-03-16

Fabrication and use of porous silicon structures to increase surface area of heated reaction chambers, electrophoresis devices, and thermopneumatic sensor-actuators, chemical preconcentrates, and filtering or control flow devices. In particular, such high surface area or specific pore size porous silicon structures will be useful in significantly augmenting the adsorption, vaporization, desorption, condensation and flow of liquids and gases in applications that use such processes on a miniature scale. Examples that will benefit from a high surface area, porous silicon structure include sample preconcentrators that are designed to adsorb and subsequently desorb specific chemical species from a sample background; chemical reaction chambers with enhanced surface reaction rates; and sensor-actuator chamber devices with increased pressure for thermopneumatic actuation of integrated membranes. Examples that benefit from specific pore sized porous silicon are chemical/biological filters and thermally-activated flow devices with active or adjacent surfaces such as electrodes or heaters. 9 figs.

Porous silicon structures with high surface area/specific pore size

DOEpatents

Northrup, M. Allen; Yu, Conrad M.; Raley, Norman F.

1999-01-01

Fabrication and use of porous silicon structures to increase surface area of heated reaction chambers, electrophoresis devices, and thermopneumatic sensor-actuators, chemical preconcentrates, and filtering or control flow devices. In particular, such high surface area or specific pore size porous silicon structures will be useful in significantly augmenting the adsorption, vaporization, desorption, condensation and flow of liquids and gasses in applications that use such processes on a miniature scale. Examples that will benefit from a high surface area, porous silicon structure include sample preconcentrators that are designed to adsorb and subsequently desorb specific chemical species from a sample background; chemical reaction chambers with enhanced surface reaction rates; and sensor-actuator chamber devices with increased pressure for thermopneumatic actuation of integrated membranes. Examples that benefit from specific pore sized porous silicon are chemical/biological filters and thermally-activated flow devices with active or adjacent surfaces such as electrodes or heaters.

Feasibility of High-Repetition, Task-Specific Training for Individuals With Upper-Extremity Paresis

PubMed Central

Waddell, Kimberly J.; Birkenmeier, Rebecca L.; Moore, Jennifer L.; Hornby, T. George

2014-01-01

OBJECTIVE. We investigated the feasibility of delivering an individualized, progressive, high-repetition upper-extremity (UE) task-specific training protocol for people with stroke in the inpatient rehabilitation setting. METHOD. Fifteen patients with UE paresis participated in this study. Task-specific UE training was scheduled for 60 min/day, 4 days/wk, during occupational therapy for the duration of a participant’s inpatient stay. During each session, participants were challenged to complete ≥300 repetitions of various tasks. RESULTS. Participants averaged 289 repetitions/session, spending 47 of 60 min in active training. Participants improved on impairment and activity level outcome measures. CONCLUSION. People with stroke in an inpatient setting can achieve hundreds of repetitions of task-specific training in 1-hr sessions. As expected, all participants improved on functional outcome measures. Future studies are needed to determine whether this high-repetition training program results in better outcomes than current UE interventions. PMID:25005508

Mesoporous carbon-supported Pd nanoparticles with high specific surface area for cyclohexene hydrogenation: Outstanding catalytic activity of NaOH-treated catalysts

NASA Astrophysics Data System (ADS)

Puskás, R.; Varga, T.; Grósz, A.; Sápi, A.; Oszkó, A.; Kukovecz, Á.; Kónya, Z.

2016-06-01

Extremely high specific surface area mesoporous carbon-supported Pd nanoparticle catalysts were prepared with both impregnation and polyol-based sol methods. The silica template used for the synthesis of mesoporous carbon was removed by both NaOH and HF etching. Pd/mesoporous carbon catalysts synthesized with the impregnation method has as high specific surface area as 2250 m2/g. In case of NaOH-etched impregnated samples, the turnover frequency of cyclohexene hydrogenation to cyclohexane at 313 K was obtained 14 molecules • site- 1 • s- 1. The specific surface area of HF-etched samples was higher compared to NaOH-etched samples. However, catalytic activity was 3-6 times higher on NaOH-etched samples compared to HF-etched samples, which can be attributed to the presence of sodium and surface hydroxylgroups of the catalysts etched with NaOH solution.

Calcium and Magnesium Ions Are Membrane-Active against Stationary-Phase Staphylococcus aureus with High Specificity

NASA Astrophysics Data System (ADS)

Xie, Yuntao; Yang, Lihua

2016-02-01

Staphylococcus aureus (S. aureus) is notorious for its ability to acquire antibiotic-resistance, and antibiotic-resistant S. aureus has become a wide-spread cause of high mortality rate. Novel antimicrobials capable of eradicating S. aureus cells including antibiotic-resistant ones are thus highly desired. Membrane-active bactericides and species-specific antimicrobials are two promising sources of novel anti-infective agents for fighting against bacterial antibiotic-resistance. We herein show that Ca2+ and Mg2+, two alkaline-earth-metal ions physiologically essential for diverse living organisms, both disrupt model S. aureus membranes and kill stationary-phase S. aureus cells, indicative of membrane-activity. In contrast to S. aureus, Escherichia coli and Bacillus subtilis exhibit unaffected survival after similar treatment with these two cations, indicative of species-specific activity against S. aureus. Moreover, neither Ca2+ nor Mg2+ lyses mouse red blood cells, indicative of hemo-compatibility. This works suggests that Ca2+ and Mg2+ may have implications in targeted eradication of S. aureus pathogen including the antibiotic-resistant ones.

Synthesis of tritium-labeled cyadox, a promising antimicrobial growth-promoting agent with high specific activity.

PubMed

Harnud, Sechenchogt; Zhang, Aiqun; Yuan, Zonghui

2018-05-23

Cyadox is a new antimicrobial growth-promoting agent for food-producing animals. Studies on radiolabeled compounds enable the use of sensitive radiometric analytical methods and help in the elucidation of metabolic and elimination pathways. In the present study, 6-[ 3 H]-cyadox with a high specific activity of 2.08 Ci/mmol was prepared by the catalytic bromine-tritium exchange of 4-bromo-2-nitroaniline followed by a three-step microscale synthesis, giving a high yield between 36.16% and 94.75%. Copyright © 2018. Published by Elsevier Ltd.

Real-Time, Single-Step Bioassay Using Nanoplasmonic Resonator With Ultra-High Sensitivity

NASA Technical Reports Server (NTRS)

Zhang, Xiang (Inventor); Chen, Fanqing Frank (Inventor); Su, Kai-Hang (Inventor); Wei, Qi-Huo (Inventor); Ellman, Jonathan A. (Inventor); Sun, Cheng (Inventor)

2014-01-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

Real-time, single-step bioassay using nanoplasmonic resonator with ultra-high sensitivity

DOEpatents

Zhang, Xiang; Ellman, Jonathan A; Chen, Fanqing Frank; Su, Kai-Hang; Wei, Qi-Huo; Sun, Cheng

2014-04-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

Cell-Selective Biological Activity of Rhodium Metalloinsertors Correlates with Subcellular Localization

PubMed Central

Komor, Alexis C.; Schneider, Curtis J.; Weidmann, Alyson G.; Barton, Jacqueline K.

2013-01-01

Deficiencies in the mismatch repair (MMR) pathway are associated with several types of cancers, as well as resistance to commonly used chemotherapeutics. Rhodium metalloinsertors have been found to bind DNA mismatches with high affinity and specificity in vitro, and also exhibit cell-selective cytotoxicity, targeting MMR-deficient cells over MMR-proficient cells. Ten distinct metalloinsertors with varying lipophilicities have been synthesized and their mismatch binding affinities and biological activities determined. Although DNA photocleavage experiments demonstrate that their binding affinities are quite similar, their cell-selective antiproliferative and cytotoxic activities vary significantly. Inductively coupled plasma mass spectrometry (ICP-MS) experiments have uncovered a relationship between the subcellular distribution of these metalloinsertors and their biological activities. Specifically, we find that all of our metalloinsertors localize in the nucleus at sufficient concentrations for binding to DNA mismatches. However, the metalloinsertors with high rhodium localization in the mitochondria show toxicity that is not selective for MMR-deficient cells, whereas metalloinsertors with less mitochondrial rhodium show activity that is highly selective for MMR-deficient versus proficient cells. This work supports the notion that specific targeting of the metalloinsertors to nuclear DNA gives rise to their cell-selective cytotoxic and antiproliferative activities. The selectivity in cellular targeting depends upon binding to mismatches in genomic DNA. PMID:23137296

A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets

PubMed Central

Jia, Dongyu; Liu, Zhenqiu; Deng, Nan; Tan, Tuan Zea; Huang, Ruby Yun-Ju; Taylor-Harding, Barbie; Cheon, Dong-Joo; Lawrenson, Kate; Wiedemeyer, Wolf R.; Walts, Ann E.; Karlan, Beth Y.; Orsulic, Sandra

2016-01-01

Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated CAFs from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second, it is unclear whether CAFs in different organs have different molecular and functional properties that necessitate organ-specific therapeutic designs. Our analyses uncovered COL11A1 as a highly specific biomarker of activated CAFs. Using COL11A1 as a ‘seed’, we identified co-expressed genes in 13 types of primary carcinoma in The Cancer Genome Atlas. We demonstrated that a molecular signature of activated CAFs is conserved in epithelial cancers regardless of organ site and transforming events within cancer cells, suggesting that targeting fibroblast activation should be effective in multiple cancers. We prioritized several potential pan-cancer therapeutic targets that are likely to have high specificity for activated CAFs and minimal toxicity in normal tissues. PMID:27609069

TNFR2-deficient memory CD8 T cells provide superior protection against tumor cell growth.

PubMed

Kim, Edward Y; Teh, Soo-Jeet; Yang, Jocelyn; Chow, Michael T; Teh, Hung-Sia

2009-11-15

TNF receptor-2 (TNFR2) plays a critical role in promoting the activation and survival of naive T cells during the primary response. Interestingly, anti-CD3 plus IL-2 activated TNFR2(-/-) CD8 T cells are highly resistant to activation-induced cell death (AICD), which correlates with high expression levels of prosurvival molecules such as Bcl-2, survivin, and CD127 (IL-7Ralpha). We determined whether the resistance of activated TNFR2(-/-) CD8 T cells to AICD contributes to more effective protection against tumor cell growth. We found that during a primary tumor challenge, despite initial inferiority in controlling tumor cell growth, TNFR2(-/-) mice were able to more effectively control tumor burden over time compared with wild-type (WT) mice. Furthermore, vaccination of TNFR2(-/-) mice with recombinant Listeria monocytogenes that express OVA confers better protection against the growth of OVA-expressing E.G7 tumor cells relative to similarly vaccinated WT mice. The enhanced protection against tumor cell growth was not due to more effective activation of OVA-specific memory CD8 T cells in vaccinated TNFR2(-/-) mice. In vitro studies indicate that optimally activated OVA-specific TNFR2(-/-) CD8 T cells proliferated to the same extent and possess similar cytotoxicity against E.G7 tumor cells as WT CD8 T cells. However, relative to WT cells, activated OVA-specific TNFR2(-/-) CD8 T cells were highly resistant to AICD. Thus, the enhanced protection against E.G7 in TNFR2(-/-) mice is likely due to the recruitment and activation of OVA-specific memory TNFR2(-/-) CD8 T cells and their prolonged survival at the tumor site.

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

PubMed Central

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

2008-01-01

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

HIGH-THROUGHPUT IDENTIFICATION OF CATALYTIC REDOX-ACTIVE CYSTEINE RESIDUES

EPA Science Inventory

Cysteine (Cys) residues often play critical roles in proteins; however, identification of their specific functions has been limited to case-by-case experimental approaches. We developed a procedure for high-throughput identification of catalytic redox-active Cys in proteins by se...

Bulk production and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 targets in a proton beam

DOE PAGES

Mastren, Tara; Radchenko, Valery; Bach, Hong T.; ...

2017-06-01

Rhenium-186 g (t 1/2 = 3.72 d) is a β– emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185Re(n,γ) 186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186W results in a 186gRe product with a much specific activity, allowing it to be used more broadly for targeted radiotherapy applications. Furthermore, this targets the unmet clinical need for more efficient radiotherapeutics.

Bulk production and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 targets in a proton beam

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

Mastren, Tara; Radchenko, Valery; Bach, Hong T.

Rhenium-186 g (t 1/2 = 3.72 d) is a β– emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185Re(n,γ) 186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186W results in a 186gRe product with a much specific activity, allowing it to be used more broadly for targeted radiotherapy applications. Furthermore, this targets the unmet clinical need for more efficient radiotherapeutics.

High-performance super capacitors based on activated anthracite with controlled porosity

NASA Astrophysics Data System (ADS)

Lee, Hyun-Chul; Byamba-Ochir, Narandalai; Shim, Wang-Geun; Balathanigaimani, M. S.; Moon, Hee

2015-02-01

Mongolian anthracite is chemically activated using potassium hydroxide as an activation agent to make activated carbon materials. Prior to the chemical activation, the chemical agent is introduced by two different methods as follows, (1) simple physical mixing, (2) impregnation. The physical properties such as specific surface area, pore volume, pore size distribution, and adsorption energy distribution are measured to assess them as carbon electrode materials for electric double-layer capacitors (EDLC). The surface functional groups and morphology are also characterized by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) analyses respectively. The electrochemical results for the activated carbon electrodes in 3 M sulfuric acid electrolyte solution indicate that the activated Mongolian anthracite has relatively large specific capacitances in the range of 120-238 F g-1 and very high electrochemical stability, as they keep more than 98% of initial capacitances until 1000 charge/discharge cycles.

Insight into the role of substrate-binding residues in conferring substrate specificity for the multifunctional polysaccharide lyase Smlt1473.

PubMed

MacDonald, Logan C; Berger, Bryan W

2014-06-27

Anionic polysaccharides are of growing interest in the biotechnology industry due to their potential pharmaceutical applications in drug delivery and wound treatment. Chemical composition and polymer length strongly influence the physical and biological properties of the polysaccharide and thus its potential industrial and medical applications. One promising approach to determining monomer composition and controlling the degree of polymerization involves the use of polysaccharide lyases, which catalyze the depolymerization of anionic polysaccharides via a β-elimination mechanism. Utilization of these enzymes for the production of custom-made oligosaccharides requires a high degree of control over substrate specificity. Previously, we characterized a polysaccharide lyase (Smlt1473) from Stenotrophomonas maltophilia k279a, which exhibited significant activity against hyaluronan (HA), poly-β-d-glucuronic acid (poly-GlcUA), and poly-β-d-mannuronic acid (poly-ManA) in a pH-regulated manner. Here, we utilize a sequence structure guided approach based on a homology model of Smlt1473 to identify nine putative substrate-binding residues and examine their effect on substrate specificity via site-directed mutagenesis. Interestingly, single point mutations H221F and R312L resulted in increased activity and specificity toward poly-ManA and poly-GlcUA, respectively. Furthermore, a W171A mutant nearly eliminated HA activity, while increasing poly-ManA and poly-GlcUA activity by at least 35%. The effect of these mutations was analyzed by comparison with the high resolution structure of Sphingomonas sp. A1-III alginate lyase in complex with poly-ManA tetrasaccharide and by taking into account the structural differences between HA, poly-GlcUA, and poly-ManA. Overall, our results demonstrate that even minor changes in active site architecture have a significant effect on the substrate specificity of Smlt1473, whose structural plasticity could be applied to the design of highly active and specific polysaccharide lyases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Organic emissions from coal pyrolysis: mutagenic effects.

PubMed Central

Braun, A G; Wornat, M J; Mitra, A; Sarofim, A F

1987-01-01

Four different types of coal have been pyrolyzed in a laminar flow, drop tube furnace in order to establish a relationship between polycyclic aromatic compound (PAC) evolution and mutagenicity. Temperatures of 900K to 1700K and particle residence times up to 0.3 sec were chosen to best simulate conditions of rapid rate pyrolysis in pulverized (44-53 microns) coal combustion. The specific mutagenic activity (i.e., the activity per unit sample weight) of extracts from particulates and volatiles captured on XAD-2 resin varied with coal type according to the order: subbituminous greater than high volatile bituminous greater than lignite greater than anthracite. Total mutagenic activity (the activity per gram of coal pyrolyzed), however, varied with coal type according to the order: high volatile bituminous much greater than subbituminous = lignite much greater than anthracite, due primarily to high organic yield during high volatile bituminous coal pyrolysis. Specific mutagenic activity peaked in a temperature range of 1300K to 1500K and generally appeared at higher temperatures and longer residence times than peak PAC production. PMID:3311724

Targeting Inhibition of Fibroblast Activation Protein-α and Prolyl Oligopeptidase Activities on Cells Common to Metastatic Tumor Microenvironments1

PubMed Central

Christiansen, Victoria J; Jackson, Kenneth W; Lee, Kyung N; Downs, Tamyra D; McKee, Patrick A

2013-01-01

Fibroblast activation protein (FAP), a membrane prolyl-specific proteinase with both dipeptidase and endopeptidase activities, is overexpressed by reactive stromal fibroblasts during epithelial-derived cancer growth. FAP digests extracellular matrix as tissue is remodeled during cancer expansion and may also promote an immunotolerant tumor microenvironment. Recent studies suggest that nonspecific FAP inhibitors suppress human cancer xenografts in mouse models. Prolyl oligopeptidase (POP), another prolyl-specific serine proteinase, is also elevated in many cancers and may have a regulatory role in angiogenesis promotion. FAP and POP cell-associated activities may be targets for diagnosis and treatment of various cancers, but their accessibilities to highly effective specific inhibitors have not been shown for cells important to cancer growth. Despite their frequent simultaneous expression in many cancers and their overlapping activities toward commonly used substrates, precise, separate measurement of FAP or POP activity has largely been ignored. To distinguish each of the two activities, we synthesized highly specific substrates and inhibitors for FAP or POP based on amino acid sequences surrounding the scissile bonds of their respective putative substrates. We found varying amounts of FAP and POP protein and activities on activated fibroblasts, mesenchymal cells, normal breast cells, and one breast cancer cell line, with some cells exhibiting more POP than FAP activity. Replicating endothelial cells (ECs) expressed POP but not FAP until tubulogenesis began. Targeting FAP-positive cells, especially mesenchymal stem cells and cancer-associated fibroblasts for inactivation or destruction, and inhibiting POP-producing EC may abrogate stromal invasion and angiogenesis simultaneously and thereby diminish cancer growth. PMID:23555181

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

Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents.

PubMed

Benoit, Stephen C; Kemp, Christopher J; Elias, Carol F; Abplanalp, William; Herman, James P; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G; Holland, William L; Clegg, Deborah J

2009-09-01

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.

Web addiction in the brain: Cortical oscillations, autonomic activity, and behavioral measures.

PubMed

Balconi, Michela; Campanella, Salvatore; Finocchiaro, Roberta

2017-09-01

Background and aims Internet addiction (IA) was recently defined as a disorder tagging both the impulse control and the reward systems. Specifically, inhibitory deficits and reward bias were considered highly relevant in IA. This research aims to examine the electrophysiological correlates and autonomic activity [skin conductance response (SCR) and heart rate] in two groups of young subjects (N = 25), with high or low IA profile [tested by the Internet Addiction Test (IAT)], with specific reference to gambling behavior. Methods Oscillatory brain activity (delta, theta, alpha, beta, and gamma) and autonomic and behavioral measures [response times (RTs) and error rates (ERs)] were acquired during the performance of a Go/NoGo task in response to high-rewarding (online gambling videos and video games) or neutral stimuli. Results A better performance (reduced ERs and reduced RTs) was revealed for high IAT in the case of NoGo trials representing rewarding cues (inhibitory control condition), probably due to a "gain effect" induced by the rewarding condition. In addition, we also observed for NoGo trials related to gambling and video games stimuli that (a) increased low-frequency band (delta and theta) and SCR and (b) a specific lateralization effect (more left-side activity) delta and theta in high IAT. Discussion Both inhibitory control deficits and reward bias effect were considered to explain IA.

Web addiction in the brain: Cortical oscillations, autonomic activity, and behavioral measures

PubMed Central

Balconi, Michela; Campanella, Salvatore; Finocchiaro, Roberta

2017-01-01

Background and aims Internet addiction (IA) was recently defined as a disorder tagging both the impulse control and the reward systems. Specifically, inhibitory deficits and reward bias were considered highly relevant in IA. This research aims to examine the electrophysiological correlates and autonomic activity [skin conductance response (SCR) and heart rate] in two groups of young subjects (N = 25), with high or low IA profile [tested by the Internet Addiction Test (IAT)], with specific reference to gambling behavior. Methods Oscillatory brain activity (delta, theta, alpha, beta, and gamma) and autonomic and behavioral measures [response times (RTs) and error rates (ERs)] were acquired during the performance of a Go/NoGo task in response to high-rewarding (online gambling videos and video games) or neutral stimuli. Results A better performance (reduced ERs and reduced RTs) was revealed for high IAT in the case of NoGo trials representing rewarding cues (inhibitory control condition), probably due to a “gain effect” induced by the rewarding condition. In addition, we also observed for NoGo trials related to gambling and video games stimuli that (a) increased low-frequency band (delta and theta) and SCR and (b) a specific lateralization effect (more left-side activity) delta and theta in high IAT. Discussion Both inhibitory control deficits and reward bias effect were considered to explain IA. PMID:28718301

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

PubMed Central

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

2015-01-01

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

Putative storage root specific promoters from cassava and yam: cloning and evaluation in transgenic carrots as a model system.

PubMed

Arango, Jacobo; Salazar, Bertha; Welsch, Ralf; Sarmiento, Felipe; Beyer, Peter; Al-Babili, Salim

2010-06-01

A prerequisite for biotechnological improvements of storage roots is the availability of tissue-specific promoters enabling high expression of transgenes. In this work, we cloned two genomic fragments, pMe1 and pDJ3S, controlling the expression of a gene with unknown function from cassava (Manihot esculenta) and of the storage protein dioscorin 3 small subunit gene from yam (Dioscorea japonica), respectively. Using beta-glucuronidase as a reporter, the activities of pMe1 and pDJ3S were evaluated in independent transgenic carrot lines and compared to the constitutive CaMV35S and the previously described cassava p15 promoters. Activities of pMe1 and pDJ3S in storage roots were assessed using quantitative GUS assays that showed pDJ3S as the most active one. To determine organ specificities, uidA transcript levels in leaves, stems and roots were measured by real-time RT-PCR analyses showing highest storage root specificity for pDJ3S. Root cross sections revealed that pMe1 was highly active in secondary xylem. In contrast, pDJ3S was active in all root tissues except for the central xylem. The expression patterns caused by the cassava p15 promoter in carrot storage roots were consistent with its previously described activities for the original storage organ. Our data demonstrate that the pDJ3S and, to a lesser extent, the pMe1 regulatory sequences represent feasible candidates to drive high and preferential expression of genes in carrot storage roots.

A doped activated carbon prepared from polyaniline for high performance supercapacitors

NASA Astrophysics Data System (ADS)

Li, Limin; Liu, Enhui; Li, Jian; Yang, Yanjing; Shen, Haijie; Huang, Zhengzheng; Xiang, Xiaoxia; Li, Wen

A novel doped activated carbon has been prepared from H 2SO 4-doped polyaniline which is prepared by the oxypolymerization of aniline. The morphology, surface chemical composition and surface area of the carbon have been investigated by scanning electron microscope, X-ray photoelectron spectroscopy and Brunaner-Emmett-Teller measurement, respectively. Electrochemical properties of the doped activated carbon have been studied by cyclic voltammograms, galvanostatic charge/discharge, and electrochemical impedance spectroscopy measurements in 6 mol l -1 KOH. The specific capacitance of the carbon is as high as 235 F g -1, the specific capacitance hardly decreases at a high current density 11 A g -1 after 10,000 cycles, which indicates that the carbon possesses excellent cycle durability and may be a promising candidate for supercapacitors.

Peripheral Blood Signatures of Lead Exposure

PubMed Central

LaBreche, Heather G.; Meadows, Sarah K.; Nevins, Joseph R.; Chute, John P.

2011-01-01

Background Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. PMID:21829687

Sulfur-doped nanoporous carbon spheres with ultrahigh specific surface area and high electrochemical activity for supercapacitor

NASA Astrophysics Data System (ADS)

Liu, Simin; Cai, Yijin; Zhao, Xiao; Liang, Yeru; Zheng, Mingtao; Hu, Hang; Dong, Hanwu; Jiang, Sanping; Liu, Yingliang; Xiao, Yong

2017-08-01

Development of facile and scalable synthesis process for the fabrication of nanoporous carbon materials with large specific surface areas, well-defined nanostructure, and high electrochemical activity is critical for the high performance energy storage applications. The key issue is the dedicated balance between the ultrahigh surface area and highly porous but interconnected nanostructure. Here, we demonstrate the fabrication of new sulfur doped nanoporous carbon sphere (S-NCS) with the ultrahigh surface area up to 3357 m2 g-1 via a high-temperature hydrothermal carbonization and subsequent KOH activation process. The as-prepared S-NCS which integrates the advantages of ultrahigh porous structure, well-defined nanospherical and modification of heteroatom displays excellent electrochemical performance. The best performance is obtained on S-NCS prepared by the hydrothermal carbonization of sublimed sulfur and glucose, S-NCS-4, reaching a high specific capacitance (405 F g-1 at a current density of 0.5 A g-1) and outstanding cycle stability. Moreover, the symmetric supercapacitor is assembled by S-NCS-4 displays a superior energy density of 53.5 Wh kg-1 at the power density of 74.2 W kg-1 in 1.0 M LiPF6 EC/DEC. The synthesis method is simple and scalable, providing a new route to prepare highly porous and heteroatom-doped nanoporous carbon spheres for high performance energy storage applications.

Specification for installation of the crew activity planning system coaxial cable communication system

NASA Technical Reports Server (NTRS)

Allen, M. A.; Roman, G. S.

1979-01-01

The specification used to install a broadband coaxial cable communication system to support remote terminal operations on the Crew Activity Planning system at the Lyndon B. Johnson Space Center are reported. The system supports high speed communications between a Harris Slash 8 computer and one or more Sanders Graphic 7 displays.

High surface area carbon and process for its production

DOEpatents

Romanos, Jimmy; Burress, Jacob; Pfeifer, Peter; Rash, Tyler; Shah, Parag; Suppes, Galen

2016-12-13

Activated carbon materials and methods of producing and using activated carbon materials are provided. In particular, biomass-derived activated carbon materials and processes of producing the activated carbon materials with prespecified surface areas and pore size distributions are provided. Activated carbon materials with preselected high specific surface areas, porosities, sub-nm (<1 nm) pore volumes, and supra-nm (1-5 nm) pore volumes may be achieved by controlling the degree of carbon consumption and metallic potassium intercalation into the carbon lattice during the activation process.

Highly effective phosphorylation by G protein-coupled receptor kinase 7 of light-activated visual pigment in cones.

PubMed

Tachibanaki, Shuji; Arinobu, Daisuke; Shimauchi-Matsukawa, Yoshie; Tsushima, Sawae; Kawamura, Satoru

2005-06-28

Cone photoreceptors show briefer photoresponses than rod photoreceptors. Our previous study showed that visual pigment phosphorylation, a quenching mechanism of light-activated visual pigment, is much more rapid in cones than in rods. Here, we measured the early time course of this rapid phosphorylation with good time resolution and directly compared it with the photoresponse time course in cones. At the time of photoresponse recovery, almost two phosphates were incorporated into a bleached cone pigment molecule, which indicated that the visual pigment phosphorylation coincides with the photoresponse recovery. The rapid phosphorylation in cones is attributed to very high activity of visual pigment kinase [G protein-coupled receptor kinase (GRK) 7] in cones. Because of this high activity, cone pigment is readily phosphorylated at very high bleach levels, which probably explains why cone photoresponses recover quickly even after a very bright light and do not saturate under intense background light. The high GRK7 activity is brought about by high content of a highly potent enzyme. The expression level of GRK7 was 10 times higher than that of rod kinase (GRK1), and the specific activity of a single GRK7 molecule was approximately 10 times higher than that of GRK1. The specific activity of GRK7 is the highest among the GRKs so far known. Our result seems to explain the response characteristics of cone photoreceptors in many aspects, including the nonsaturation of the cone responses during daylight vision.

Factorial effects of salinity, dietary carbohydrate and moult cycle on digestive carbohydrases and hexokinases in Litopenaeus vannamei (Boone, 1931).

PubMed

Gaxiola, Gabriela; Cuzon, Gerard; García, Tomás; Taboada, Gabriel; Brito, Roberto; Chimal, María Eugenia; Paredes, Adriana; Soto, Luis; Rosas, Carlos; van Wormhoudt, Alain

2005-01-01

Litopenaeus vannamei were reared in close cycle over seven generations and tested for their capacity to digest starch and to metabolise glucose at different stages of the moulting cycle. After acclimation with 42.3% of carbohydrates (HCBH) or 2.3% carbohydrates (LCBH) diets and at high salinity (40 g kg(-1)) or low salinity (15 g kg(-1)), shrimp were sampled and hepatopancreas (HP) were stored. Total soluble protein in HP was affected by the interaction between salinity and moult stages (p<0.05). Specific activity of alpha-amylase ranged from 44 to 241 U mg protein(-1) and a significant interaction between salinity and moult stages was observed (p<0.05), resulting in highest values at stage C for low salinity (mean value 196.4 U mg protein(-1)), and at D0 in high salinity (mean value 175.7 U mg protein(-1)). Specific activity of alpha-glucosidase ranged between 0.09 and 0.63 U mg protein(-1), an interaction between dietary CBH and salinity was observed for the alpha-glucosidase (p<0.05) and highest mean value was found in low salinity-LCBH diet treatment (0.329 U mg protein(-1)). Hexokinase specific activity (range 9-113 mU mg protein(-1)) showed no significant differences when measured at 5 mM glucose (p>0.05). Total hexokinase specific activity (range 17-215 mU mg protein(-1)) showed a significant interaction between dietary CBH and salinity (p<0.05) with highest value (mean value 78.5 mU mg protein(-1)) found in HCBH-high salinity treatment, whereas in the other treatments the activity was not significantly different (mean value 35.93 mU mg protein(-1)). A synergistic effect of dietary CBH, salinity and moult stages over hexokinase IV-like specific activity was also observed (p<0.05). As result of this interaction, the highest value (135.5+/-81 mU mg protein(-1)) was observed in HCBH, high salinity at D0 moult stage. Digestive enzymes activity is enhanced in the presence of high starch diet (HCBH) and hexokinase can be induced at certain moulting stages under the influence of blood glucose level. Perspectives are opened to add more carbohydrates in a growing diet, exemplifying the potential approach for less-polluting feed.

Expanding the Bioactive Chemical Space of Anthrabenzoxocinones through Engineering the Highly Promiscuous Biosynthetic Modification Steps.

PubMed

Mei, Xianyi; Yan, Xiaoli; Zhang, Hui; Yu, Mingjia; Shen, Guangqing; Zhou, Linjun; Deng, Zixin; Lei, Chun; Qu, Xudong

2018-01-19

Anthrabenzoxocinones (ABXs) including (-)-ABXs and (+)-ABXs are a group of bacterial FabF-specific inhibitors with potent antimicrobial activity of resistant strains. Optimization of their chemical structures is a promising method to develop potent antibiotics. Through biosynthetic investigation, we herein identified and characterized two highly promiscuous enzymes involved in the (-)-ABX structural modification. The promiscuous halogenase and methyltransferase can respectively introduce halogen-modifications into various positions of the ABX scaffolds and methylation to highly diverse substrates. Manipulation of their activity in both of the (-)-ABXs and (+)-ABXs biosyntheses led to the generation of 14 novel ABX analogues of both enantiomers. Bioactivity assessment revealed that a few of the analogues showed significantly improved antimicrobial activity, with the C3-hydroxyl and chlorine substitutions critical for their activity. This study enormously expands the bioactive chemical space of the ABX family and FabF-specific inhibitors. The disclosed broad-selective biosynthetic machineries and structure-activity relationship provide a solid basis for further generation of potent antimicrobial agents.

Individual, Social, and Environmental Correlates of Active Transportation Patterns in French Women.

PubMed

Perchoux, Camille; Enaux, Christophe; Oppert, Jean-Michel; Menai, Mehdi; Charreire, Hélène; Salze, Paul; Weber, Christiane; Hercberg, Serge; Feuillet, Thierry; Hess, Franck; Roda, Célina; Simon, Chantal; Nazare, Julie-Anne

2017-01-01

The objectives were (1) to define physical activity (PA) and sedentary behaviors (SB) patterns in daily life contexts (work, leisure, and transportation) in French working women from NutriNet-Santé web-cohort and (2) to identify pattern(s) of active transportation and their individual, social, and environmental correlates. 23,432 participants completed two questionnaires to evaluate PA and SB in daily life contexts and individual representations of residential neighborhood and transportation modes. Hierarchical cluster analysis was performed which identified 6 distinct movement behavior patterns: (i) active occupation, high sedentary leisure, (ii) sedentary occupation, low leisure, (iii) sedentary transportation, (iv) sedentary occupation and leisure, (v) active transportation, and (vi) active leisure. Multinomial logistic regressions were performed to identify correlates of the "active transportation" cluster. The perceived environmental characteristics positively associated with "active transportation" included "high availability of destinations around home," "presence of bicycle paths," and "low traffic." A "positive image of walking/cycling," the "individual feeling of being physically active," and a "high use of active transport modes by relatives/friends" were positively related to "active transportation," identified as a unique pattern regarding individual and environmental correlates. Identification of PA and SB context-specific patterns will help to understand movement behaviors' complexity and to design interventions to promote active transportation in specific subgroups.

In vitro selection of high temperature Zn(2+)-dependent DNAzymes.

PubMed

Nelson, Kevin E; Bruesehoff, Peter J; Lu, Yi

2005-08-01

In vitro selection of Zn(2+)-dependent RNA-cleaving DNAzymes with activity at 90 degrees C has yielded a diverse spool of selected sequences. The RNA cleavage efficiency was found in all cases to be specific for Zn(2+) over Pb(2+), Ca(2+), Cd(2+), Co(2+), Hg(2+), and Mg(2+). The Zn(2+)-dependent activity assay of the most active sequence showed that the DNAzyme possesses an apparent Zn(2+)-binding dissociation constant of 234 muM and that its activity increases with increasing temperatures from 50-90 degrees C. A fit of the Arrhenius plot data gave E(a) = 15.3 kcal mol(-1). Surprisingly, the selected Zn(2+)-dependent DNAzymes showed only a modest (approximately 3-fold) activity enhancement over the background rate of cleavage of random sequences containing a single embedded ribonucleotide within an otherwise DNA oligonucleotide. The result is attributable to the ability of DNA to sustain cleavage activity at high temperature with minimal secondary structure when Zn(2+) is present. Since this effect is highly specific for Zn(2+), this metal ion may play a special role in molecular evolution of nucleic acids at high temperature.

High cancer-specific expression of mesothelin (MSLN) is attributable to an upstream enhancer containing a transcription enhancer factor dependent MCAT motif.

PubMed

Hucl, Tomas; Brody, Jonathan R; Gallmeier, Eike; Iacobuzio-Donahue, Christine A; Farrance, Iain K; Kern, Scott E

2007-10-01

Identification of genes with cancer-specific overexpression offers the potential to efficiently discover cancer-specific activities in an unbiased manner. We apply this paradigm to study mesothelin (MSLN) overexpression, a nearly ubiquitous, diagnostically and therapeutically useful characteristic of pancreatic cancer. We identified an 18-bp upstream enhancer, termed CanScript, strongly activating transcription from an otherwise weak tissue-nonspecific promoter and operating selectively in cells having aberrantly elevated cancer-specific MSLN transcription. Introducing mutations into CanScript showed two functionally distinct sites: an Sp1-like site and an MCAT element. Gel retardation and chromatin immunoprecipitation assays showed the MCAT element to be bound by transcription enhancer factor (TEF)-1 (TEAD1) in vitro and in vivo. The presence of TEF-1 was required for MSLN protein overexpression as determined by TEF-1 knockdown experiments. The cancer specificity seemed to be provided by a putative limiting cofactor of TEF-1 that could be outcompeted by exogenous TEF-1 only in a MSLN-overexpressing cell line. A CanScript concatemer offered enhanced activity. These results identify a TEF family member as a major regulator of MSLN overexpression, a fundamental characteristic of pancreatic and other cancers, perhaps due to an upstream and highly frequent aberrant cellular activity. The CanScript sequence represents a modular element for cancer-specific targeting, potentially suitable for nearly a third of human malignancies.

A simple physical mechanism enables homeostasis in primitive cells

NASA Astrophysics Data System (ADS)

Engelhart, Aaron E.; Adamala, Katarzyna P.; Szostak, Jack W.

2016-05-01

The emergence of homeostatic mechanisms that enable maintenance of an intracellular steady state during growth was critical to the advent of cellular life. Here, we show that concentration-dependent reversible binding of short oligonucleotides, of both specific and random sequence, can modulate ribozyme activity. In both cases, catalysis is inhibited at high concentrations, and dilution activates the ribozyme via inhibitor dissociation, thus maintaining near-constant ribozyme specific activity throughout protocell growth. To mimic the result of RNA synthesis within non-growing protocells, we co-encapsulated high concentrations of ribozyme and oligonucleotides within fatty acid vesicles, and ribozyme activity was inhibited. Following vesicle growth, the resulting internal dilution produced ribozyme activation. This simple physical system enables a primitive homeostatic behaviour: the maintenance of constant ribozyme activity per unit volume during protocell volume changes. We suggest that such systems, wherein short oligonucleotides reversibly inhibit functional RNAs, could have preceded sophisticated modern RNA regulatory mechanisms, such as those involving miRNAs.

Activated graphene as a cathode material for Li-ion hybrid supercapacitors.

PubMed

Stoller, Meryl D; Murali, Shanthi; Quarles, Neil; Zhu, Yanwu; Potts, Jeffrey R; Zhu, Xianjun; Ha, Hyung-Wook; Ruoff, Rodney S

2012-03-14

Chemically activated graphene ('activated microwave expanded graphite oxide', a-MEGO) was used as a cathode material for Li-ion hybrid supercapacitors. The performance of a-MEGO was first verified with Li-ion electrolyte in a symmetrical supercapacitor cell. Hybrid supercapacitors were then constructed with a-MEGO as the cathode and with either graphite or Li(4)Ti(5)O(12) (LTO) for the anode materials. The results show that the activated graphene material works well in a symmetrical cell with the Li-ion electrolyte with specific capacitances as high as 182 F g(-1). In a full a-MEGO/graphite hybrid cell, specific capacitances as high as 266 F g(-1) for the active materials at operating potentials of 4 V yielded gravimetric energy densities for a packaged cell of 53.2 W h kg(-1).

Production Of High Specific Activity Copper-67

DOEpatents

Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

2002-12-03

A process for the selective production and isolation of high specific activity cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

Production Of High Specific Activity Copper-67

DOEpatents

Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

2003-10-28

A process for the selective production and isolation of high specific activity Cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

Design and Development of "The Reading Biographer": An Application of Function Specific Assessment.

ERIC Educational Resources Information Center

Hanson, Ralph A.; Siegel, Donna Farrell

The general features of function-specific assessment are described and illustrated via a discussion of the design and development of "The Reading Biographer," an instrument for assessing experiences and activities of students (from early childhood through high school) that affect their reading achievement as high school seniors. The…

A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface.

PubMed

Warfield, Linda; Tuttle, Lisa M; Pacheco, Derek; Klevit, Rachel E; Hahn, Steven

2014-08-26

Although many transcription activators contact the same set of coactivator complexes, the mechanism and specificity of these interactions have been unclear. For example, do intrinsically disordered transcription activation domains (ADs) use sequence-specific motifs, or do ADs of seemingly different sequence have common properties that encode activation function? We find that the central activation domain (cAD) of the yeast activator Gcn4 functions through a short, conserved sequence-specific motif. Optimizing the residues surrounding this short motif by inserting additional hydrophobic residues creates very powerful ADs that bind the Mediator subunit Gal11/Med15 with high affinity via a "fuzzy" protein interface. In contrast to Gcn4, the activity of these synthetic ADs is not strongly dependent on any one residue of the AD, and this redundancy is similar to that of some natural ADs in which few if any sequence-specific residues have been identified. The additional hydrophobic residues in the synthetic ADs likely allow multiple faces of the AD helix to interact with the Gal11 activator-binding domain, effectively forming a fuzzier interface than that of the wild-type cAD.

Leisure-time physical activity and psychological well-being in university students.

PubMed

Molina-García, J; Castillo, I; Queralt, A

2011-10-01

An analysis of psychological well-being (self-esteem and subjective vitality) of 639 Spanish university students was performed, while accounting for the amount of leisure-time physical activity. The Spanish versions of the Rosenberg Self-Esteem Scale and Subjective Vitality Scale were employed. Participants were divided into four groups (Low, Moderate, High, and Very high) depending on estimation of energy expenditure in leisure-time physical activity. Men and women having higher physical activity rated higher mean subjective vitality; however, differences in self-esteem were observed only in men, specifically between Very high and the other physical activity groups.

A Highly Active and Negatively Charged Streptococcus pyogenes Lysin with a Rare d-Alanyl-l-Alanine Endopeptidase Activity Protects Mice against Streptococcal Bacteremia

PubMed Central

Lood, Rolf; Raz, Assaf; Molina, Henrik; Euler, Chad W.

2014-01-01

Bacteriophage endolysins have shown great efficacy in killing Gram-positive bacteria. PlyC, a group C streptococcal phage lysin, represents the most efficient lysin characterized to date, with a remarkably high specificity against different streptococcal species, including the important pathogen Streptococcus pyogenes. However, PlyC is a unique lysin, in terms of both its high activity and structure (two distinct subunits). We sought to discover and characterize a phage lysin active against S. pyogenes with an endolysin architecture distinct from that of PlyC to determine if it relies on the same mechanism of action as PlyC. In this study, we identified and characterized an endolysin, termed PlyPy (phage lysin from S. pyogenes), from a prophage infecting S. pyogenes. By in silico analysis, PlyPy was found to have a molecular mass of 27.8 kDa and a pI of 4.16. It was active against a majority of group A streptococci and displayed high levels of activity as well as binding specificity against group B and C streptococci, while it was less efficient against other streptococcal species. PlyPy showed the highest activity at neutral pH in the presence of calcium and NaCl. Surprisingly, its activity was not affected by the presence of the group A-specific carbohydrate, while the activity of PlyC was partly inhibited. Additionally, PlyPy was active in vivo and could rescue mice from systemic bacteremia. Finally, we developed a novel method to determine the peptidoglycan bond cleaved by lysins and concluded that PlyPy exhibits a rare d-alanyl-l-alanine endopeptidase activity. PlyPy thus represents the first lysin characterized from Streptococcus pyogenes and has a mechanism of action distinct from that of PlyC. PMID:24637688

A highly active and negatively charged Streptococcus pyogenes lysin with a rare D-alanyl-L-alanine endopeptidase activity protects mice against streptococcal bacteremia.

PubMed

Lood, Rolf; Raz, Assaf; Molina, Henrik; Euler, Chad W; Fischetti, Vincent A

2014-06-01

Bacteriophage endolysins have shown great efficacy in killing Gram-positive bacteria. PlyC, a group C streptococcal phage lysin, represents the most efficient lysin characterized to date, with a remarkably high specificity against different streptococcal species, including the important pathogen Streptococcus pyogenes. However, PlyC is a unique lysin, in terms of both its high activity and structure (two distinct subunits). We sought to discover and characterize a phage lysin active against S. pyogenes with an endolysin architecture distinct from that of PlyC to determine if it relies on the same mechanism of action as PlyC. In this study, we identified and characterized an endolysin, termed PlyPy (phage lysin from S. pyogenes), from a prophage infecting S. pyogenes. By in silico analysis, PlyPy was found to have a molecular mass of 27.8 kDa and a pI of 4.16. It was active against a majority of group A streptococci and displayed high levels of activity as well as binding specificity against group B and C streptococci, while it was less efficient against other streptococcal species. PlyPy showed the highest activity at neutral pH in the presence of calcium and NaCl. Surprisingly, its activity was not affected by the presence of the group A-specific carbohydrate, while the activity of PlyC was partly inhibited. Additionally, PlyPy was active in vivo and could rescue mice from systemic bacteremia. Finally, we developed a novel method to determine the peptidoglycan bond cleaved by lysins and concluded that PlyPy exhibits a rare d-alanyl-l-alanine endopeptidase activity. PlyPy thus represents the first lysin characterized from Streptococcus pyogenes and has a mechanism of action distinct from that of PlyC. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Mammalian transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes and are predicted to act as transcriptional activator hubs.

PubMed

Joshi, Anagha

2014-12-30

Transcriptional hotspots are defined as genomic regions bound by multiple factors. They have been identified recently as cell type specific enhancers regulating developmentally essential genes in many species such as worm, fly and humans. The in-depth analysis of hotspots across multiple cell types in same species still remains to be explored and can bring new biological insights. We therefore collected 108 transcription-related factor (TF) ChIP sequencing data sets in ten murine cell types and classified the peaks in each cell type in three groups according to binding occupancy as singletons (low-occupancy), combinatorials (mid-occupancy) and hotspots (high-occupancy). The peaks in the three groups clustered largely according to the occupancy, suggesting priming of genomic loci for mid occupancy irrespective of cell type. We then characterized hotspots for diverse structural functional properties. The genes neighbouring hotspots had a small overlap with hotspot genes in other cell types and were highly enriched for cell type specific function. Hotspots were enriched for sequence motifs of key TFs in that cell type and more than 90% of hotspots were occupied by pioneering factors. Though we did not find any sequence signature in the three groups, the H3K4me1 binding profile had bimodal peaks at hotspots, distinguishing hotspots from mono-modal H3K4me1 singletons. In ES cells, differentially expressed genes after perturbation of activators were enriched for hotspot genes suggesting hotspots primarily act as transcriptional activator hubs. Finally, we proposed that ES hotspots might be under control of SetDB1 and not DNMT for silencing. Transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes. In ES cells, they are predicted to act as transcriptional activator hubs and might be under SetDB1 control for silencing.

Radical Prostatectomy Findings in Men on Active Surveillance: Variable Findings Dependent on Reason for Surgery and Entry Criteria.

PubMed

Matoso, Andres; Hassan, Oudai; Petrozzino, Florencia; Rao, B Vishal; Carter, H Ballentine; Epstein, Jonathan I

2015-09-01

We studied adverse radical prostatectomy findings in men on an active surveillance program with different entry and exit criteria. The study included 80 men with biopsy progression, 33 who opted out for personal reasons and 24 who initially did not meet entry criteria mainly due to increased prostate specific antigen density. Of men who opted out 78.8% had a higher Gleason score of 6 than men who progressed on biopsy (46.2%, p = 0.002) and men with high prostate specific antigen density (45.8%, p = 0.02). Men with high prostate specific antigen density had less organ confined disease than the group that opted out (p <0.006) and a trend compared to the biopsy progression group (p = 0.07). Mean dominant tumor volume was lower in men who opted out than in those with biopsy progression (0.56 vs 1.1 cc, p = 0.03). The incidence of insignificant cancer was higher in men who opted out (48.4%) than in those with biopsy progression (28.4%, p = 0.05) and those with high prostate specific antigen density (20.8%, p = 0.035). There was a higher incidence of anterior tumor in men with high prostate specific antigen density (55.0%) than with biopsy progression (21.3%, p = 0.009) and a trend compared to those who opted out (27.3%, p = 0.06). The majority of men with biopsy progression still had tumors with features of curable disease. Men who opted out without biopsy progression had even less adverse findings, which supports counseling men to stay on active surveillance while they meet followup criteria. Men with elevated prostate specific antigen density had more anterior tumors and less organ confined cancer, substantiating that the ideal patients for active surveillance are those who meet all entry criteria. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Detection of collaborative activity with Kinect depth cameras.

PubMed

Sevrin, Loic; Noury, Norbert; Abouchi, Nacer; Jumel, Fabrice; Massot, Bertrand; Saraydaryan, Jacques

2016-08-01

The health status of elderly subjects is highly correlated to their activities together with their social interactions. Thus, the long term monitoring in home of their health status, shall also address the analysis of collaborative activities. This paper proposes a preliminary approach of such a system which can detect the simultaneous presence of several subjects in a common area using Kinect depth cameras. Most areas in home being dedicated to specific tasks, the localization enables the classification of tasks, whether collaborative or not. A scenario of a 24 hours day shrunk into 24 minutes was used to validate our approach. It pointed out the need of artifacts removal to reach high specificity and good sensitivity.

Three-dimensional porous activated carbon derived from loofah sponge biomass for supercapacitor applications

NASA Astrophysics Data System (ADS)

Su, Xiao-Li; Chen, Jing-Ran; Zheng, Guang-Ping; Yang, Jing-He; Guan, Xin-Xin; Liu, Pu; Zheng, Xiu-Cheng

2018-04-01

Biomass carbon source is generally cheap, environmentally friendly and readily available in high quality and quantity. In this work, a series of loofah sponge-derived activated carbon (SAC-x) with hierarchical porous structures are prepared by KOH chemical activation and used as electrode materials for supercapacitors. The pore size can be easily controllable by changing the dosage of KOH. The optimized material (SAC-4) exhibits a high specific capacitance of 309.6 F g-1 at 1 A g-1 in the three-electrode system using 6 M KOH electrolyte. More importantly, the as-assembled symmetric supercapacitor based on SAC-4 exhibits a high energy density of 16.1 Wh kg-1 at a power density of 160.0 W kg-1 using 1 M Na2SO4 electrolyte. These remarkable results demonstrate the exciting commercial potential of SAC-x for high-performance supercapacitor applications due to their high specific surface area, appropriately porous structure, and the trace heteroatom (O and N) functionalities.

Electrospinning Fabrication of SrTiO3 Nanofibers and Their Photocatalytic Activity

NASA Astrophysics Data System (ADS)

Xu, Lei; Zhao, Yiping; Wang, Wei; Liu, Hao; Wang, Rui

2018-06-01

SrTiO3 nanofibers were fabricated by an electrospinning process. The phase, microstructure and photocatalytic activity of the obtained SrTiO3 nanofibers were investigated. The XRD patterns and the SEM images suggest that SrTiO3 nanofibers with perovskite phase and rough surface have been fabricated in the current work. The SrTiO3 nanofibers show a high efficiency decomposition of RhB under ultraviolet light irradiation. The high photocatalytic activity of SrTiO3 nanofibers results from the large specific surface area. The large specific surface area provides more surface active sits and makes an easier charge carrier transport. On the basis of the photocatalytic performance of SrTiO3 nanofibers, the possible photocatalysis mechanism was proposed.

Binding of the host-specific toxins from Helminthosporium maydis race T and Phyllosticta maydis to mitochondria isolated from Zea mays

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

Frantzen, K.A.

1985-01-01

Helminthosphorium maydis race I and Phyllosticta maydis, the causal agents of southern and yellow corn leaf blights, respectively, produce host-specific toxins. The toxic specificity of these natural products is identical to the host-specificity of the pathogens for certain varieties of corn. Susceptible genotypes carry the Texas type of cytoplasmic male sterility. Isolated mitochondria from susceptible plant species are highly sensitive to these toxins, whereas other plant species, including resistant corn varieties, and their mitochondria are not. The mitochondrion may be the primary cellular site of action for these toxins. The toxins from H. maydis and P. maydis were tritiated bymore » reduction with borotritide salts. The labeled products had a high specific activity (3.8 to 8 Ci/mmole), high biological activity, and specificity identical to that of the native toxins. A filtration binding assay was developed to investigate the binding characteristics of these labeled toxins to isolated mitochondria. Mitochondria isolated from both cytoplasmic male sterile (Texas) and normal corn demonstrated similar binding characteristics including ligand displaceable binding with both labeled toxins. Ligand displaceable binding was also detectable in mitochondria from soybeans, a nonhost plant for these fungi. The ability to displace the bound labeled toxins was generally correlated with the biological activity of the competing toxin. The results of this study suggest that a receptor site hypothesis for the mode of action of these toxins may not be valid.« less

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

NASA Astrophysics Data System (ADS)

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

2000-07-01

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

Hierarchically porous nitrogen-doped carbon derived from the activation of agriculture waste by potassium hydroxide and urea for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Zou, Kaixiang; Deng, Yuanfu; Chen, Juping; Qian, Yunqian; Yang, Yuewang; Li, Yingwei; Chen, Guohua

2018-02-01

Nitrogen-doped carbon with an ultra-high specific surface area and a hierarchically interconnected porous structure is synthesized in large scale from a green route, that is, the activation of bagasse via a one-step method using KOH and urea. KOH and urea play a synergistic effect for the enhancement of the specific surface area and the modification of pore size of the as-prepared material. Benefiting from the multiple synergistic roles originated from an ultra-high specific area (2905.4 m2 g-1), a high porous volume (2.05 mL g-1 with 75.6 vol% micropores, which is an ideal proportion of micropores for obtaining high specific capacitance), a suitable nitrogen content (2.63 wt%), and partial graphitization, the hierarchically interconnected porous N-doped carbon exhibits an excellent electrochemical performance with a high specific capacitance (350.8, 301.9, and 259.5 F g-1 at 1.0 A g-1 in acidic, alkaline, and neutral electrolytes, respectively), superior rate capability and excellent cycling stability (almost no capacitance loss up to 5000 cycles). Furthermore, the symmetric device assembled by this material achieves high energy densities of 39.1 and 23.5 Wh kg-1 at power densities of 1.0 and 20 kW kg-1, respectively, and exhibits an excellent long-term cycling stability (with capacitance retention above 95.0% after 10 000 cycles).

Focus on Freshman: Basic Instruction Programs Enhancing Physical Activity

ERIC Educational Resources Information Center

Curry, Jarred; Jenkins, Jayne M.; Weatherford, Jennifer

2015-01-01

Physical activity sharply decreases after different life stages, particularly high school graduation to beginning university education. The purpose of this study was to investigate the effect of a specifically designed university physical activity class, Exercise Planning for Freshman (EPF), on students' physical activity and group cohesion…

A Haloalkane Dehalogenase from a Marine Microbial Consortium Possessing Exceptionally Broad Substrate Specificity.

PubMed

Buryska, Tomas; Babkova, Petra; Vavra, Ondrej; Damborsky, Jiri; Prokop, Zbynek

2018-01-15

The haloalkane dehalogenase enzyme DmmA was identified by marine metagenomic screening. Determination of its crystal structure revealed an unusually large active site compared to those of previously characterized haloalkane dehalogenases. Here we present a biochemical characterization of this interesting enzyme with emphasis on its structure-function relationships. DmmA exhibited an exceptionally broad substrate specificity and degraded several halogenated environmental pollutants that are resistant to other members of this enzyme family. In addition to having this unique substrate specificity, the enzyme was highly tolerant to organic cosolvents such as dimethyl sulfoxide, methanol, and acetone. Its broad substrate specificity, high overexpression yield (200 mg of protein per liter of cultivation medium; 50% of total protein), good tolerance to organic cosolvents, and a broad pH range make DmmA an attractive biocatalyst for various biotechnological applications. IMPORTANCE We present a thorough biochemical characterization of the haloalkane dehalogenase DmmA from a marine metagenome. This enzyme with an unusually large active site shows remarkably broad substrate specificity, high overexpression, significant tolerance to organic cosolvents, and activity under a broad range of pH conditions. DmmA is an attractive catalyst for sustainable biotechnology applications, e.g., biocatalysis, biosensing, and biodegradation of halogenated pollutants. We also report its ability to convert multiple halogenated compounds to corresponding polyalcohols. Copyright © 2018 American Society for Microbiology.

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

PubMed Central

Jayasooriya, Shamanthi; de Silva, Thushan I.; Njie-jobe, Jainaba; Sanyang, Chilel; Leese, Alison M.; Bell, Andrew I.; McAulay, Karen A.; Yanchun, Peng; Long, Heather M.; Dong, Tao; Whittle, Hilton C.; Rickinson, Alan B.; Rowland-Jones, Sarah L.; Hislop, Andrew D.; Flanagan, Katie L.

2015-01-01

Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14–18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms. PMID:25816224

Micro-mesoporous carbon spheres derived from carrageenan as electrode material for supercapacitors

NASA Astrophysics Data System (ADS)

Fan, Yang; Yang, Xin; Zhu, Bing; Liu, Pei-Fang; Lu, Hai-Ting

2014-12-01

The polysaccharide carrageenan is used as a natural precursor to prepare micro-mesoporous carbon spheres. The carbon spheres were synthesized by hydrothermal carbonization of carrageenan, and subsequent chemical activation by KOH at different temperatures. The obtained micro-mesoporous carbon spheres have high surface area (up to 2502 m2 g-1) and large pore volume (up to 1.43 cm3 g-1). Moreover, the micro- and mesoporosity can be finely tuned be modifying the activation temperatures in the range of 700-900 °C. The carbon spheres activated at 900 °C present high specific capacitance of 230 F g-1 at a current density of 1 A g-1 and good ion transport kinetics. The good capacitive performance can be ascribed to the high specific surface area, well-controlled micro- and mesoporosity and narrow pore size distribution.

The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at promoters.

PubMed

Li, Tianlu; De Clercq, Nikki; Medina, Daniel A; Garre, Elena; Sunnerhagen, Per; Pérez-Ortín, José E; Alepuz, Paula

2016-02-01

The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1, which controls most gene expression changes during osmostress, and observe that deletion of CBC1 delays the accumulation of the activator complex Hot1-Hog1 at osmostress promoters. Additionally, CBC1 deletion specifically reduces transcription rates of highly transcribed genes under non-stress conditions, such as ribosomal protein (RP) genes, while having low impact on transcription of weakly expressed genes. For RP genes, we show that recruitment of the specific activator Rap1, and subsequently TBP, to promoters is Cbc1-dependent. Altogether, our results indicate that binding of Cbc1 to the capped mRNAs is necessary for the accumulation of specific activators as well as PIC components at the promoters of genes whose expression requires high and rapid transcription. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Identification of a dual-specificity protein phosphatase that inactivates a MAP kinase from Arabidopsis

NASA Technical Reports Server (NTRS)

Gupta, R.; Huang, Y.; Kieber, J.; Luan, S.; Evans, M. L. (Principal Investigator)

1998-01-01

Mitogen-activated protein kinases (MAPKs) play a key role in plant responses to stress and pathogens. Activation and inactivation of MAPKs involve phosphorylation and dephosphorylation on both threonine and tyrosine residues in the kinase domain. Here we report the identification of an Arabidopsis gene encoding a dual-specificity protein phosphatase capable of hydrolysing both phosphoserine/threonine and phosphotyrosine in protein substrates. This enzyme, designated AtDsPTP1 (Arabidopsis thaliana dual-specificity protein tyrosine phosphatase), dephosphorylated and inactivated AtMPK4, a MAPK member from the same plant. Replacement of a highly conserved cysteine by serine abolished phosphatase activity of AtDsPTP1, indicating a conserved catalytic mechanism of dual-specificity protein phosphatases from all eukaryotes.

Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy

PubMed Central

Wagner, Kay-Dietrich; Vukolic, Ana; Baudouy, Delphine; Michiels, Jean-François

2016-01-01

Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease. PMID:27057154

Changes in plasma chemistry after drug-induced liver disease or muscle necrosis in racing pigeons (Columba livia domestica).

PubMed

Lumeij, J T; Meidam, M; Wolfswinkel, J; Van der Hage, M H; Dorrestein, G M

1988-01-01

Changes in plasma variables as a result of liver damage induced by ethylene glycol (group A) or D-galactosamine (group B) and of muscle damage induced by doxycycline were compared. Plasma bile acid concentration was both a specific and a sensitive indicator of liver disease. Another specific, but less sensitive indicator of liver disease was 7-GT. Plasma AS AT activity was the most sensitive indicator of disease of the liver, but was not specific, since increased ASAT activities were also seen during muscle disease. ALAT activity was slightly more sensitive to liver damage than 7-GT, but was also not specific, being increased also after muscle damage. Plasma GLDH activity was increased only as a result of extensive liver necrosis. AP activity was of no value for detecting liver disease in the pigeon. CK activity was specific for muscle injury, though the activities of ALAT, ASAT and LD were also increased. Because of its long elimination half-life, increased ALAT activity persisted for 9 days after muscle damage, whereas CK activity returned to reference values within 3 days. LDH was a poor indicator of damage to liver and muscle, despite its relatively high tissue concentrations in both tissues. The rapid disappearance rate of LDH from plasma probably explains this observation.

Screening bioactivity and bioactive constituents of Nordic unifloral honeys.

PubMed

Salonen, Anneli; Virjamo, Virpi; Tammela, Päivi; Fauch, Laure; Julkunen-Tiitto, Riitta

2017-12-15

The objective of this study was to screen the antibacterial and antioxidant activity of thirty nine honey samples from Finland, Sweden, Norway and Denmark. Their physicochemical properties were analysed, antioxidant activity was evaluated by DPPH assay and antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus was assessed by microdilution assay. The honey samples obtained were buckwheat, caraway, clover, dandelion, fireweed, heather, lime tree, lingonberry, rape, raspberry, sweet clover, willow, mire, honeydew and polyfloral. Eleven honey samples showed high antioxidant activity. With 15% honey dilution, three unifloral honeys had over 85% inhibition against growth of P. aeruginosa and ten honey samples against S. aureus. The buckwheat, raspberry and honeydew honeys showed the highest antibacterial and antioxidant activity. An unexpectedly high amount of methylglyoxal was found in mire and forest honeys. Some phenolic compounds are shown to be plant species-specific floral markers due to their appearance in specific unifloral honey samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

GC/MS analysis of high-performance liquid chromatography fractions from Sophora flavescens and Torilis japonica extracts and their in vitro anti-neosporal effects on Neospora caninum.

PubMed

Seo, Hun-Su; Kim, Kyoung Hee; Kim, Dae-Yong; Park, Bong-Kyun; Shin, Nam-Shik; Kim, Jae-Hoon; Youn, Heejeong

2013-01-01

We analyzed alcoholic extracts of herbs possessing anti-neosporal activity against Neospora (N.) caninum. To identify the chemical components of Sophora (S.) flavescens and Torilis (T.) japonica associated with anti-neosporal activity, specific fractions were isolated by high-performance liquid chromatography (HPLC). In vitro activity of the fractions against N. caninum was then assessed. Gas chromatography/ mass spectrometry (GC/MS) was used to identify and quantify specific anti-neosporal molecules in the herbal extracts. Almost all HPLC fractions of S. flavescens and T. japonica had higher levels of anti-neosporal activity compared to the not treated control. Active constituents of the extracts were sophoridane, furosardonin A, and tetraisopropylidene-cyclobutane in S. flavescens; 5,17-β-dihydroxy-de-A-estra-5,7,9,14-tetraene, furanodiene, and 9,12-octadecadienoic acid (Z,Z)-(CAS,1) in T. japonica.

GC/MS analysis of high-performance liquid chromatography fractions from Sophora flavescens and Torilis japonica extracts and their in vitro anti-neosporal effects on Neospora caninum

PubMed Central

Seo, Hun-Su; Kim, Kyoung Hee; Kim, Dae-Yong; Park, Bong-Kyun; Shin, Nam-Shik; Kim, Jae-Hoon

2013-01-01

We analyzed alcoholic extracts of herbs possessing anti-neosporal activity against Neospora (N.) caninum. To identify the chemical components of Sophora (S.) flavescens and Torilis (T.) japonica associated with anti-neosporal activity, specific fractions were isolated by high-performance liquid chromatography (HPLC). In vitro activity of the fractions against N. caninum was then assessed. Gas chromatography/mass spectrometry (GC/MS) was used to identify and quantify specific anti-neosporal molecules in the herbal extracts. Almost all HPLC fractions of S. flavescens and T. japonica had higher levels of anti-neosporal activity compared to the not treated control. Active constituents of the extracts were sophoridane, furosardonin A, and tetraisopropylidene-cyclobutane in S. flavescens; 5,17-β-dihydroxy-de-A-estra-5,7,9,14-tetraene, furanodiene, and 9,12-octadecadienoic acid (Z,Z)-(CAS,1) in T. japonica. PMID:23820198

Tunable porous structure of carbon nanosheets derived from puffed rice for high energy density supercapacitors

NASA Astrophysics Data System (ADS)

Hou, Jianhua; Jiang, Kun; Tahir, Muhammad; Wu, Xiaoge; Idrees, Faryal; Shen, Ming; Cao, Chuanbao

2017-12-01

The development of green and clean synthetic techniques to overcome energy requirements have motivated the researchers for the utilization of sustainable biomass. Driven by this desire we choose rice as starting materials source. After the explosion effect, the precursor is converted into puffed rice with a honeycomb-like structures composed of thin sheets. These honeycomb-like macrostructures, effectively prevent the cross-linking tendency towards the adjacent nanosheets during activation process. Furthermore, tuneable micro/mesoporous structures with ultrahigh specific surface areas (SBET) are successfully designed by KOH activation. The highest SBET of 3326 m2 g-1 with optimized proportion of small-mesopores is achieved at 850 °C. The rice-derived porous N-doped carbon nanosheets (NCS-850) are used as the active electrode materials for supercapacitors. It exhibites high specific capacitance specifically of 218 F g-1 at 80 A g-1 in 6 M KOH and a high-energy density of 104 Wh kg-1 (53 Wh L-1) in the ionic liquid electrolytes. These are the highest values among the reported biomass-derived carbon materials for the best of our knowledge. The present work demonstrates that the combination of "puffing effect" and common chemical activation can turn natural products such as rice into functional products with prospective applications in high-performance energy storage devices.

Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

PubMed Central

Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

2009-01-01

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-θ attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-θ activation, resulting in reduced insulin activity. PMID:19726875

Serine Protease Inhibitors Specifically Defend Solanum nigrum against Generalist Herbivores but Do Not Influence Plant Growth and Development[C][W

PubMed Central

Hartl, Markus; Giri, Ashok P.; Kaur, Harleen; Baldwin, Ian T.

2010-01-01

Solanaceaeous taxa produce diverse peptide serine proteinase inhibitors (SPIs), known antidigestive defenses that might also control endogenous plant proteases. If and how a plant coordinates and combines its different SPIs for the defense against herbivores and if these SPIs simultaneously serve developmental functions is unknown. We examine Solanum nigrum’s SPI profile, comprising four different active inhibitors, of which the most abundant proved to be novel, to understand their functional specialization in an ecological context. Transcript and activity characterization revealed tissue-specific and insect-elicited accumulation patterns. Stable and transient gene silencing of all four SPIs revealed different specificities for target proteinases: the novel SPI2c displayed high specificity for trypsin and chymotrypsin, while two other SPI2 homologs were highly active against subtilisin. In field and lab experiments, we found all four SPIs to display herbivore- and gene-specific defensive properties, with dissimilar effects on closely related species. However, we did not observe any clear developmental phenotype in SPI-silenced plants, suggesting that SPIs do not play a major role in regulating endogenous proteases under the conditions studied. In summary, specific single SPIs or their combinations defend S. nigrum against generalist herbivores, while the defense against herbivores specialized on SPI-rich diets requires other unknown defense mechanisms. PMID:21177479

Characterization of a bacterial tannase from Streptococcus gallolyticus UCN34 suitable for tannin biodegradation.

PubMed

Jiménez, Natalia; Barcenilla, José María; de Felipe, Félix López; de Las Rivas, Blanca; Muñoz, Rosario

2014-01-01

The gene in the locus GALLO_1609 from Streptococcus gallolyticus UCN34 was cloned and expressed as an active protein in Escherichia coli BL21 (DE3). The protein was named TanSg1 since it shows similarity to bacterial tannases previously described. The recombinant strain produced His-tagged TanSg1 which was purified by affinity chromatography. Purified TanSg1 protein showed tannase activity, having a specific activity of 577 U/mg which is 41 % higher than the activity of Lactobacillus plantarum tannase. Remarkably, TanSg1 displayed optimum catalytic activity at pH 6-8 and 50-70 °C and showed high stability over a broad range of temperatures. It retained 25 % of its relative activity after prolonged incubation at 45 °C. The specific activity of TanSg1 is enhanced by the divalent cation Ca(2+) and is dramatically reduced by Zn(2+) and Hg(2+). The enzyme was highly specific for gallate and protocatechuate esters and showed no catalytic activity against other phenolic esters. The protein TanSg1 hydrolyzes efficiently tannic acid, a complex and polymeric gallotanin, allowing its complete conversion to gallic acid, a potent antioxidant. From its biochemical properties, TanSg1 is a tannase with potential industrial interest regarding the biodegradation of tannin waste or its bioconversion into biologically active products.

Nutrition Education: Choose Well, Be Well. A Curriculum Guide for High School.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento.

This curriculum guide for high school students contains 20 information acquisition lessons, 6 values awareness lessons, and 5 open-ended discussion lessons. Some lessons contain activities that extend over several days; other lessons contain one specific activity. The nutrition education goals are directed toward the attainment of nutrition…

Nutrition Education: Choose Well, Be Well. A Curriculum Guide for Junior High School.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento.

This curriculum guide for junior high school students contains 17 information acquisition lessons, 5 values awareness lessons, and 6 open-ended discussion lessons. Some lessons contain activities that extend over several days; other lessons contain one specific activity. The nutrition education goals are directed toward the attainment of nutrition…

Aptamer-mediated 'turn-off/turn-on' nanozyme activity of gold nanoparticles for kanamycin detection.

PubMed

Sharma, Tarun Kumar; Ramanathan, Rajesh; Weerathunge, Pabudi; Mohammadtaheri, Mahsa; Daima, Hemant Kumar; Shukla, Ravi; Bansal, Vipul

2014-12-28

A new ultrafast and highly sensitive 'turn-off/turn-on' biosensing approach that combines the intrinsic peroxidase-like activity of gold nanoparticles (GNPs) with the high affinity and specificity of a ssDNA aptamer is presented for the efficient detection of a model small molecule kanamycin.

Stimulating ammonia oxidizing bacteria (AOB) activity drives the ammonium oxidation rate in a constructed wetland (CW).

PubMed

Su, Yu; Wang, Weidong; Wu, Di; Huang, Wei; Wang, Mengzi; Zhu, Guibing

2018-05-15

An integrated approach to document high ammonium oxidation rate in Guanjinggang constructed wetland (GJG-CW) was performed and the results showed that the substantial ammonium oxidation rate could be obtained by enhancing Ammonia Oxidizing Bacteria (AOB) activity rather than Ammonia Oxidizing Archaea (AOA) activity. In the plant-bed/ditch system, ditch center and plant-bed fringe were two active zones for NH 4 + -N removal with ammonium oxidation rate peaking at 2.98±0.04 and 2.15±0.02mgNkg -1 d -1 , respectively. The enhanced AOB activity were achieved by increasing water level fluctuations, extending hydraulic retention time (HRT) and stimulating substrate availability, which subsequently enhanced NH 4 + -N removal by 34.06% in GJG-CW. However, the high AOB activity was not correlated with high AOB abundance, but was instead mostly determined by specific AOB taxa, particularly Nitrosomonas, which dominated in the active AOB. The increased cell-specific AOA activity and high AOA diversity were also achieved using those engineering measures. Although the AOA activity decreased overall with extended HRT and increased NH 4 + -N contents in GJG-CW, AOA still played a major role on ammonium oxidation in plant-bed soil. The study illustrated that artificially enhancing AOB activity and certain species in anthropogenically polluted water ecosystems would be an effective strategy to improve NH 4 + -N removal. Copyright © 2017 Elsevier B.V. All rights reserved.

Individual, Social, and Environmental Correlates of Active Transportation Patterns in French Women

PubMed Central

Perchoux, Camille; Enaux, Christophe; Oppert, Jean-Michel; Menai, Mehdi; Charreire, Hélène; Salze, Paul; Weber, Christiane; Hercberg, Serge; Feuillet, Thierry; Hess, Franck; Roda, Célina; Simon, Chantal

2017-01-01

The objectives were (1) to define physical activity (PA) and sedentary behaviors (SB) patterns in daily life contexts (work, leisure, and transportation) in French working women from NutriNet-Santé web-cohort and (2) to identify pattern(s) of active transportation and their individual, social, and environmental correlates. 23,432 participants completed two questionnaires to evaluate PA and SB in daily life contexts and individual representations of residential neighborhood and transportation modes. Hierarchical cluster analysis was performed which identified 6 distinct movement behavior patterns: (i) active occupation, high sedentary leisure, (ii) sedentary occupation, low leisure, (iii) sedentary transportation, (iv) sedentary occupation and leisure, (v) active transportation, and (vi) active leisure. Multinomial logistic regressions were performed to identify correlates of the “active transportation” cluster. The perceived environmental characteristics positively associated with “active transportation” included “high availability of destinations around home,” “presence of bicycle paths,” and “low traffic.” A “positive image of walking/cycling,” the “individual feeling of being physically active,” and a “high use of active transport modes by relatives/friends” were positively related to “active transportation,” identified as a unique pattern regarding individual and environmental correlates. Identification of PA and SB context-specific patterns will help to understand movement behaviors' complexity and to design interventions to promote active transportation in specific subgroups. PMID:28717653

Activation of context-specific attentional control sets by exogenous allocation of visual attention to the context?

PubMed

Gottschalk, Caroline; Fischer, Rico

2017-03-01

Different contexts with high versus low conflict frequencies require a specific attentional control involvement, i.e., strong attentional control for high conflict contexts and less attentional control for low conflict contexts. While it is assumed that the corresponding control set can be activated upon stimulus presentation at the respective context (e.g., upper versus lower location), the actual features that trigger control set activation are to date not described. Here, we ask whether the perceptual priming of the location context by an abrupt onset of irrelevant stimuli is sufficient in activating the context-specific attentional control set. For example, the mere onset of a stimulus might disambiguate the relevant location context and thus, serve as a low-level perceptual trigger mechanism that activates the context-specific attentional control set. In Experiment 1 and 2, the onsets of task-relevant and task-irrelevant (distracter) stimuli were manipulated at each context location to compete for triggering the activation of the appropriate control set. In Experiment 3, a prior training session enabled distracter stimuli to establish contextual control associations of their own before entering the test session. Results consistently showed that the mere onset of a task-irrelevant stimulus (with or without a context-control association) is not sufficient to activate the context-associated attentional control set by disambiguating the relevant context location. Instead, we argue that the identification of the relevant stimulus at the respective context is a precondition to trigger the activation of the context-associated attentional control set.

Carbohydrate Recognition Specificity of Trans-sialidase Lectin Domain from Trypanosoma congolense

PubMed Central

Waespy, Mario; Gbem, Thaddeus T.; Elenschneider, Leroy; Jeck, André-Philippe; Day, Christopher J.; Hartley-Tassell, Lauren; Bovin, Nicolai; Tiralongo, Joe; Haselhorst, Thomas; Kelm, Sørge

2015-01-01

Fourteen different active Trypanosoma congolense trans-sialidases (TconTS), 11 variants of TconTS1 besides TconTS2, TconTS3 and TconTS4, have been described. Notably, the specific transfer and sialidase activities of these TconTS differ by orders of magnitude. Surprisingly, phylogenetic analysis of the catalytic domains (CD) grouped each of the highly active TconTS together with the less active enzymes. In contrast, when aligning lectin-like domains (LD), the highly active TconTS grouped together, leading to the hypothesis that the LD of TconTS modulates its enzymatic activity. So far, little is known about the function and ligand specificity of these LDs. To explore their carbohydrate-binding potential, glycan array analysis was performed on the LD of TconTS1, TconTS2, TconTS3 and TconTS4. In addition, Saturation Transfer Difference (STD) NMR experiments were done on TconTS2-LD for a more detailed analysis of its lectin activity. Several mannose-containing oligosaccharides, such as mannobiose, mannotriose and higher mannosylated glycans, as well as Gal, GalNAc and LacNAc containing oligosaccharides were confirmed as binding partners of TconTS1-LD and TconTS2-LD. Interestingly, terminal mannose residues are not acceptor substrates for TconTS activity. This indicates a different, yet unknown biological function for TconTS-LD, including specific interactions with oligomannose-containing glycans on glycoproteins and GPI anchors found on the surface of the parasite, including the TconTS itself. Experimental evidence for such a scenario is presented. PMID:26474304

Extracurricular Activities and High School Dropouts.

ERIC Educational Resources Information Center

McNeal, Ralph B., Jr.

1995-01-01

Reports on a study of 14,249 students to determine whether participation in specific extracurricular activities (athletics and fine arts) significantly reduces a student's likelihood of dropping out. Finds that, when all activities are examined, only athletic participation remains significantly related to dropping out. (ACM)

Predictive factors of the nursing diagnosis sedentary lifestyle in people with high blood pressure.

PubMed

Guedes, Nirla Gomes; Lopes, Marcos Venícios de Oliveira; Araujo, Thelma Leite de; Moreira, Rafaella Pessoa; Martins, Larissa Castelo Guedes

2011-01-01

To verify the reproducibility of defining the characteristics and related factors in order to identify a sedentary lifestyle in patients with high blood pressure. A cross-sectional study. 310 patients diagnosed with high blood pressure. Socio-demographics and variables related to defining the characteristics and related factors of a sedentary lifestyle. The coefficient Kappa was utilized to analyze the reproducibility. The sensitivity, specificity, and predictive value of the defining characteristics were also analyzed. Logistic regression was applied in the analysis of possible predictors. The defining characteristic with the greatest sensitivity was demonstrates physical deconditioning (98.92%). The characteristics chooses a daily routine lacking physical exercise and verbalizes preference for activities low in physical activity presented higher values of specificity (99.21% and 95.97%, respectively). The following indicators were identified as powerful predictors (85.2%) for the identification of a sedentary lifestyle: demonstrates physical deconditioning, verbalizes preference for activities low in physical activity, and lack of training for accomplishment of physical exercise. © 2010 Wiley Periodicals, Inc.

Bacterial activity in sea ice and open water of the Weddell Sea, Antarctica: A microautoradiographic study.

PubMed

Grossmann, S

1994-07-01

Metabolic activity of bacteria was investigated in open water, newly forming sea ice, and successive stages of pack ice in the Weddell Sea. Microautoradiography, using [(3)H]leucine as substrate, was compared with incorporation rates of [(3)H]leucine into proteins. Relation of [(3)H]leucine incorporation to the biomass of active bacteria provides information about changes of specific metabolic activity of cells. During a phytoplankton bloom in an ice-free, stratified water column, total numbers of bacteria in the euphotic zone averaged 2.3 × 10(5) ml(-1), but only about 13% showed activity via leucine uptake. Growth rate of the active bacteria was estimated as 0.3-0.4 days(-1). Total cell concentration of bacteria in 400 m depth was 6.6 × 10(4) ml(-1). Nearly 50% of these cells were active, although biomass production and specific growth rate were only about one-tenth that of the surface populations. When sea ice was forming in high concentrations of phytoplankton, bacterial biomass in the newly formed ice was 49.1 ng C ml(-1), exceeding that in open water by about one order of magnitude. Attachment of large bacteria to algal cells seems to cause their enrichment in the new ice, since specific bacterial activity was reduced during ice formation, and enrichment of bacteria was not observed when ice formed at low algal concentration. During growth of pack ice, biomass of bacteria increased within the brine channel system. Specific activity was still reduced at these later stages of ice development, and percentages of active cells were as low as 3-5%. In old, thick pack ice, bacterial activity was high and about 30% of cells were active. However, biomass-specific activity of bacteria remained significantly lower than that in open water. It is concluded that bacterial assemblages different to those of open water developed within the ice and were dominated by bacteria with lower average metabolic activity than those of ice-free water.

SYNTHESIS OF H$sup 3$-LABELED AMINO ACIDS WITH HIGH SPECIFIC ACTIVITY AND THEIR APPLICATION FOR HISTOAUTORADIOGRAPHY

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

Hempel, K.

1962-01-01

New methods for synthesis of tritium-labeled amino acids with high specific activity (1000 mc/m mole and above) are described. Changes in tritium- labeled amino acids during storage are studied. An absorbed BETA energy of 10/ sup 5/ rad results in radiochemical disintegration of 1.5%. Autoradiographic studies were made with several amino acids. It was demonstrated that protein production is 2 to 3 times higher in butter-vellux, tumors than in liver tissue. Synthesis of melanine was studied in vivo with melanineproducing tumors. (Gmelin Inst.)

NMR and Bioinformatics Discovery of Exosites That Tune Metalloelastase Specificity for Solubilized Elastin and Collagen Triple Helices*

PubMed Central

Palmier, Mark O.; Fulcher, Yan G.; Bhaskaran, Rajagopalan; Duong, Vinh Q.; Fields, Gregg B.; Van Doren, Steven R.

2010-01-01

The catalytic domain of metalloelastase (matrix metalloproteinase-12 or MMP-12) is unique among MMPs in exerting high proteolytic activity upon fibrils that resist hydrolysis, especially elastin from lungs afflicted with chronic obstructive pulmonary disease or arteries with aneurysms. How does the MMP-12 catalytic domain achieve this specificity? NMR interface mapping suggests that α-elastin species cover the primed subsites, a strip across the β-sheet from β-strand IV to the II–III loop, and a broad bowl from helix A to helix C. The many contacts may account for the comparatively high affinity, as well as embedding of MMP-12 in damaged elastin fibrils in vivo. We developed a strategy called BINDSIght, for bioinformatics and NMR discovery of specificity of interactions, to evaluate MMP-12 specificity without a structure of a complex. BINDSIght integration of the interface mapping with other ambiguous information from sequences guided choice mutations in binding regions nearer the active site. Single substitutions at each of ten locations impair specific activity toward solubilized elastin. Five of them impair release of peptides from intact elastin fibrils. Eight lesions also impair specific activity toward triple helices from collagen IV or V. Eight sites map to the “primed” side in the III–IV, V–B, and S1′ specificity loops. Two map to the “unprimed” side in the IV–V and B–C loops. The ten key residues circumscribe the catalytic cleft, form an exosite, and are distinctive features available for targeting by new diagnostics or therapeutics. PMID:20663866

High-Performance Supercapacitor Electrode Based on Cobalt Oxide-Manganese Dioxide-Nickel Oxide Ternary 1D Hybrid Nanotubes.

PubMed

Singh, Ashutosh K; Sarkar, Debasish; Karmakar, Keshab; Mandal, Kalyan; Khan, Gobinda Gopal

2016-08-17

We report a facile method to design Co3O4-MnO2-NiO ternary hybrid 1D nanotube arrays for their application as active material for high-performance supercapacitor electrodes. This as-prepared novel supercapacitor electrode can store charge as high as ∼2020 C/g (equivalent specific capacitance ∼2525 F/g) for a potential window of 0.8 V and has long cycle stability (nearly 80% specific capacitance retains after successive 5700 charge/discharge cycles), significantly high Coulombic efficiency, and fast response time (∼0.17s). The remarkable electrochemical performance of this unique electrode material is the outcome of its enormous reaction platform provided by its special nanostructure morphology and conglomeration of the electrochemical properties of three highly redox active materials in a single unit.

Association of dietary pattern and physical activity level with triglyceride to high-density lipoprotein cholesterol ratio among adults in Jiangsu, China: a cross-sectional study with sex-specific differences.

PubMed

Lyu, Shurong; Su, Jian; Xiang, Quanyong; Wu, Ming

2014-08-01

Our study aims to explore the association between dietary patterns and physical activity levels (PAL) with a triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and to examine whether the association is sex dependent among Chinese adults. In this cross-sectional study, data were collected through questionnaires, anthropometric measurement, and biochemical tests. Four food patterns ("meat," "healthy," "high-energy," and "traditional Chinese") were established through factor analysis. Physical activity level was categorized as "active," "moderate," and "inactive." Logistic regression models were used to determine the associations between food patterns and PAL with TG/HDL-C ratio. Compared with quartile 1, quartiles 2 and 3 of meat pattern among men were found to be associated with lower risk of high TG/HDL-C ratio (the highest quartile of TG/HDL-C ratio). Similar decreased risk of high TG/HDL-C ratio was also observed in the highest quartile 4 of healthy pattern among women. Active PAL was protective against high TG/HDL-C ratio among both men (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.55-0.86) and women (OR, 0.77; 95% CI, 0.62-0.96). Although no statistically significant interaction was observed, we found that individuals with active PAL and low healthy diet had a similar OR with those with inactive PAL and high healthy diet (0.62 vs 0.68). In conclusion, dietary patterns were associated with TG/HDL-C ratio in a sex-specific way, and active PAL was consistently related to decreased risk of high TG/HDL-C ratio across genders. Copyright © 2014 Elsevier Inc. All rights reserved.

Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study

PubMed Central

Knoops, Sofie; Aldinucci Buzzo, João L.; Boon, Lise; Martens, Erik; Opdenakker, Ghislain; Kolaczkowska, Elzbieta

2017-01-01

Gelatinase B or matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin) and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM), the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2) activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations. PMID:28369077

Identification of STAT1 and STAT3 Specific Inhibitors Using Comparative Virtual Screening and Docking Validation

PubMed Central

Szelag, Malgorzata; Czerwoniec, Anna; Wesoly, Joanna; Bluyssen, Hans A. R.

2015-01-01

Signal transducers and activators of transcription (STATs) facilitate action of cytokines, growth factors and pathogens. STAT activation is mediated by a highly conserved SH2 domain, which interacts with phosphotyrosine motifs for specific STAT-receptor contacts and STAT dimerization. The active dimers induce gene transcription in the nucleus by binding to a specific DNA-response element in the promoter of target genes. Abnormal activation of STAT signaling pathways is implicated in many human diseases, like cancer, inflammation and auto-immunity. Searches for STAT-targeting compounds, exploring the phosphotyrosine (pTyr)-SH2 interaction site, yielded many small molecules for STAT3 but sparsely for other STATs. However, many of these inhibitors seem not STAT3-specific, thereby questioning the present modeling and selection strategies of SH2 domain-based STAT inhibitors. We generated new 3D structure models for all human (h)STATs and developed a comparative in silico docking strategy to obtain further insight into STAT-SH2 cross-binding specificity of a selection of previously identified STAT3 inhibitors. Indeed, by primarily targeting the highly conserved pTyr-SH2 binding pocket the majority of these compounds exhibited similar binding affinity and tendency scores for all STATs. By comparative screening of a natural product library we provided initial proof for the possibility to identify STAT1 as well as STAT3-specific inhibitors, introducing the ‘STAT-comparative binding affinity value’ and ‘ligand binding pose variation’ as selection criteria. In silico screening of a multi-million clean leads (CL) compound library for binding of all STATs, likewise identified potential specific inhibitors for STAT1 and STAT3 after docking validation. Based on comparative virtual screening and docking validation, we developed a novel STAT inhibitor screening tool that allows identification of specific STAT1 and STAT3 inhibitory compounds. This could increase our understanding of the functional role of these STATs in different diseases and benefit the clinical need for more drugable STAT inhibitors with high specificity, potency and excellent bioavailability. PMID:25710482

What contributes to action plan enactment? Examining characteristics of physical activity plans.

PubMed

Fleig, Lena; Gardner, Benjamin; Keller, Jan; Lippke, Sonia; Pomp, Sarah; Wiedemann, Amelie U

2017-11-01

Individuals with chronic conditions can benefit from formulating action plans to engage in regular physical activity. However, the content and the successful translation of plans into action, so-called plan enactment, are rarely adequately evaluated. The aim of this study was to describe the content of user-specified plans and to examine whether participants were more likely to enact their plans if these plans were highly specific, viable, and instrumental. The study presents secondary analyses from a larger behavioural intervention in cardiac and orthopaedic rehabilitation. The content of 619 action plans from 229 participants was evaluated by two independent raters (i.e., qualitative analyses and ratings of specificity) and by participants themselves (i.e., instrumentality and viability). Plan enactment was also measured via self-reports. Multilevel analyses examined the relationship between these plan characteristics and subsequent plan enactment, and between plan enactment and aggregated physical activity. Participants preferred to plan leisure-time physical activities anchored around time-based cues. Specificity of occasion cues (i.e., when to act) and highly instrumental plans were positively associated with plan enactment. Interestingly, individuals who planned less specific behavioural responses (i.e., what to do) were more likely to enact their plans. Plan enactment was positively associated with aggregated behaviour. Interventions should not only emphasize the importance of planning, but also the benefits of formulating specific contextual cues. Planning of the behavioural response seems to require less precision. Allowing for some flexibility in executing the anticipated target behaviour seems to aid successful plan enactment. Statement of Contribution What is already known on this subject? Action planning interventions are efficacious in promoting health behaviour. Characteristics of plan content (i.e., specificity) matter for unconditional behaviour change. Plan enactment (i.e., degree to which plan is followed through) is positively linked to behaviour change. What does this study add? Specificity of occasion cues (i.e., when to act) and highly instrumental plans were positively associated with plan enactment. Individuals who planned less specific behavioural responses (i.e., what to do) were more likely to enact their plans. Planning interventions should focus on specificity of context cues but flexibility of behavioural action. © 2017 The British Psychological Society.

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

PubMed Central

Spengler, Sarah; Mess, Filip; Woll, Alexander

2015-01-01

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

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer.

PubMed

Yu, Jiwoong; Kwon, Young Suk; Kim, Sinae; Han, Christopher Sejong; Farber, Nicholas; Kim, Jongmyung; Byun, Seok Soo; Kim, Wun-Jae; Jeon, Seong Soo; Kim, Isaac Yi

2016-05-01

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible for active surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20 ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Biomass-derived nitrogen-doped porous carbons with tailored hierarchical porosity and high specific surface area for high energy and power density supercapacitors

NASA Astrophysics Data System (ADS)

Sun, Junting; Niu, Jin; Liu, Mengyue; Ji, Jing; Dou, Meiling; Wang, Feng

2018-01-01

Porous carbon materials with hierarchical structures attract intense interest for the development of high-performance supercapacitors. Herein, we demonstrate a facile and efficient strategy to synthesize nitrogen-doped hierarchically porous carbons with tailored porous structure combined with high specific surface area (SSA), which involves a pre-carbonization and a subsequent carbonization combined with KOH activation of silkworm cocoon precursors. Through adjusting the mass ratio of the activator (KOH) to pre-carbonized precursor in the activation process, the hierarchically porous carbon prepared at the mass ratio of 2 (referred to as NHPC-2) possesses a high defect density and a high SSA of 3386 m2 g-1 as well as the relatively high volumetric proportion of mesopores and macropores (45.5%). As a result, the energy density and power density of the symmetric supercapacitor based on NHPC-2 electrode are as high as 34.41 Wh kg-1 and 31.25 kW kg-1 in organic-solvent electrolyte, and are further improved to 112.1 Wh kg-1 and 23.91 kW kg-1 in ionic-liquid electrolyte.

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

H3PO4 solution hydrothermal carbonization combined with KOH activation to prepare argy wormwood-based porous carbon for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Dai, Changchao; Wan, Jiafeng; Yang, Juan; Qu, Shanshan; Jin, Tieyu; Ma, Fangwei; Shao, Jinqiu

2018-06-01

In this work, argy wormwood-based porous carbon electrode materials for high-performance supercapacitors are prepared through H3PO4 solution hydrothermal carbonization and subsequent KOH activation. The obtained carbon has a specific surface area (SSA) of 927 m2 g-1, a total pore volume of 0.56 cm3 g-1, and a high oxygen (9.38%) content. In three-electrode system, it exhibits specific capacitance of 344 F g-1 at 1 A g-1. Moreover, the symmetric supercapacitor shows an excellent rate capability of 87% retention from 1 A g-1 to 10 A g-1, and a good cycling performance with 91.6% retention over 5000 cycles in 6 M KOH. Therefore, the sample activated by H3PO4 & KOH exhibits an excellent future in energy storage.

Oxygen Reduction Reaction Activity of Platinum Thin Films with Different Densities

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

Ergul, Busra; Begum, Mahbuba; Kariuki, Nancy

Platinum thin films with different densities were grown on glassy carbon electrodes by high pressure sputtering deposition and evaluated as oxygen reduction reaction catalysts for polymer electrolyte fuel cells using cyclic voltammetry and rotating disk electrode techniques in aqueous perchloric acid electrolyte. The electrochemically active surface area, ORR mass activity (MA) and specific activity (SA) of the thin film electrodes were obtained. MA and SA were found to be higher for low-density films than for high-density film.

Mapping lexical-semantic networks and determining hemispheric language dominance: Do task design, sex, age, and language performance make a difference?

PubMed

Chang, Yu-Hsuan A; Javadi, Sogol S; Bahrami, Naeim; Uttarwar, Vedang S; Reyes, Anny; McDonald, Carrie R

2018-04-01

Blocked and event-related fMRI designs are both commonly used to localize language networks and determine hemispheric dominance in research and clinical settings. We compared activation profiles on a semantic monitoring task using one of the two designs in a total of 43 healthy individual to determine whether task design or subject-specific factors (i.e., age, sex, or language performance) influence activation patterns. We found high concordance between the two designs within core language regions, including the inferior frontal, posterior temporal, and basal temporal region. However, differences emerged within inferior parietal cortex. Subject-specific factors did not influence activation patterns, nor did they interact with task design. These results suggest that despite high concordance within perisylvian regions that are robust to subject-specific factors, methodological differences between blocked and event-related designs may contribute to parietal activations. These findings provide important information for researchers incorporating fMRI results into meta-analytic studies, as well as for clinicians using fMRI to guide pre-surgical planning. Copyright © 2018 Elsevier Inc. All rights reserved.

Multi-Compartmentalisation in the MAPK Signalling Pathway Contributes to the Emergence of Oscillatory Behaviour and to Ultrasensitivity

PubMed Central

Shuaib, Aban; Hartwell, Adam; Kiss-Toth, Endre; Holcombe, Mike

2016-01-01

Signal transduction through the Mitogen Activated Protein Kinase (MAPK) pathways is evolutionarily highly conserved. Many cells use these pathways to interpret changes to their environment and respond accordingly. The pathways are central to triggering diverse cellular responses such as survival, apoptosis, differentiation and proliferation. Though the interactions between the different MAPK pathways are complex, nevertheless, they maintain a high level of fidelity and specificity to the original signal. There are numerous theories explaining how fidelity and specificity arise within this complex context; spatio-temporal regulation of the pathways and feedback loops are thought to be very important. This paper presents an agent based computational model addressing multi-compartmentalisation and how this influences the dynamics of MAPK cascade activation. The model suggests that multi-compartmentalisation coupled with periodic MAPK kinase (MAPKK) activation may be critical factors for the emergence of oscillation and ultrasensitivity in the system. Finally, the model also establishes a link between the spatial arrangements of the cascade components and temporal activation mechanisms, and how both contribute to fidelity and specificity of MAPK mediated signalling. PMID:27243235

Lacrimal secretory IgA in active posterior uveitis induced by Toxoplasma gondii.

PubMed

Lynch, Maria Isabel; Cordeiro, Francisco; Ferreira, Silvana; Ximenes, Ricardo; Oréfice, Fernando; Malagueño, Elizabeth

2004-12-01

It is quite difficult to diagnose active toxoplasmosis in patients with ocular toxoplasmosis. Active posterior uveitis presumably due to Toxoplasma gondii infection (APUPT) is seldom produced during a prime-infection; hence most patients do not show high IgM antibodies. High levels of IgA have been described in active toxoplasmosis. The purpose of this study was to investigate possible association between APUPT and the specific anti-parasite sIgA in tears. The study was carried out as case-control. Tears of 25 clinically confirmed APUPT patients and 50 healthy control subjects were analyzed. All were IgG seropositive. Specific sIgA was determined by ELISA assay using T. gondii RH strain crude extract. Anti-T. gondii sIgA was found in 84% of the cases and in 22% of the control subjects. The intensity of the reaction was higher in APUPT cases (P = 0.007). There was strong association between APUPT patients and lacrimal sIgA (odds-ratio 18.61, P = 0.0001). ELISA test sensitivity was 84% and specificity 78%. Our data suggest that anti-T.gondii secretory IgA found in tears may become an important marker for active ocular toxoplasmosis.

Flute type micropores activated carbon from cotton stalk for high performance supercapacitors

NASA Astrophysics Data System (ADS)

Tian, Xun; Ma, Hongru; Li, Zhe; Yan, Shaocun; Ma, Lei; Yu, Feng; Wang, Gang; Guo, Xuhong; Ma, Yanqing; Wong, Chingping

2017-08-01

Flute type micropores activated carbon (FTMAC) has been successfully obtained from cotton stalk via KOH-chemical activation method. The synthesized carbon material exhibits an ordered pore structure with high specific surface area of 1964.46 m2 g-1 and pore volume of 1.03 m3 g-1. The assembled FTMAC-based electrode delivers a high specific capacitance of 254 F g-1 at a current density of 0.2 A g-1 in 1 M H2SO4 aqueous electrolyte. It still can maintain 221 F g-1at a current density of 10 A g-1, demonstrating a good rate capacity (87% retention), as well as long cyclic stability of 96% capacitance retention after 10000 charging and discharging cycles at current density of 1 A g-1. Moreover, the symmetric supercapacitor can deliver a high energy density of 18.14 W h kg-1 and a power density of 450.37 W kg-1 which is operated in the voltage range of 0-1.8 V.

Role of Architecture in the Function and Specificity of Two Notch-Regulated Transcriptional Enhancer Modules

PubMed Central

Liu, Feng; Posakony, James W.

2012-01-01

In Drosophila melanogaster, cis-regulatory modules that are activated by the Notch cell–cell signaling pathway all contain two types of transcription factor binding sites: those for the pathway's transducing factor Suppressor of Hairless [Su(H)] and those for one or more tissue- or cell type–specific factors called “local activators.” The use of different “Su(H) plus local activator” motif combinations, or codes, is critical to ensure that only the correct subset of the broadly utilized Notch pathway's target genes are activated in each developmental context. However, much less is known about the role of enhancer “architecture”—the number, order, spacing, and orientation of its component transcription factor binding motifs—in determining the module's specificity. Here we investigate the relationship between architecture and function for two Notch-regulated enhancers with spatially distinct activities, each of which includes five high-affinity Su(H) sites. We find that the first, which is active specifically in the socket cells of external sensory organs, is largely resistant to perturbations of its architecture. By contrast, the second enhancer, active in the “non-SOP” cells of the proneural clusters from which neural precursors arise, is sensitive to even simple rearrangements of its transcription factor binding sites, responding with both loss of normal specificity and striking ectopic activity. Thus, diverse cryptic specificities can be inherent in an enhancer's particular combination of transcription factor binding motifs. We propose that for certain types of enhancer, architecture plays an essential role in determining specificity, not only by permitting factor–factor synergies necessary to generate the desired activity, but also by preventing other activator synergies that would otherwise lead to unwanted specificities. PMID:22792075

A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson’s disease models

NASA Astrophysics Data System (ADS)

Li, Lin; Zhang, Cheng-Wu; Chen, Grace Y. J.; Zhu, Biwei; Chai, Chou; Xu, Qing-Hua; Tan, Eng-King; Zhu, Qing; Lim, Kah-Leong; Yao, Shao Q.

2014-02-01

The unusually high MAO-B activity consistently observed in Parkinson’s disease (PD) patients has been proposed as a biomarker; however, this has not been realized due to the lack of probes suitable for MAO-B-specific detection in live cells/tissues. Here we report the first two-photon, small molecule fluorogenic probe (U1) that enables highly sensitive/specific and real-time imaging of endogenous MAO-B activities across biological samples. We also used U1 to confirm the reported inverse relationship between parkin and MAO-B in PD models. With no apparent toxicity, U1 may be used to monitor MAO-B activities in small animals during disease development. In clinical samples, we find elevated MAO-B activities only in B lymphocytes (not in fibroblasts), hinting that MAO-B activity in peripheral blood cells might be an accessible biomarker for rapid detection of PD. Our results provide important starting points for using small molecule imaging techniques to explore MAO-B at the organism level.

A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson's disease models.

PubMed

Li, Lin; Zhang, Cheng-Wu; Chen, Grace Y J; Zhu, Biwei; Chai, Chou; Xu, Qing-Hua; Tan, Eng-King; Zhu, Qing; Lim, Kah-Leong; Yao, Shao Q

2014-01-01

The unusually high MAO-B activity consistently observed in Parkinson's disease (PD) patients has been proposed as a biomarker; however, this has not been realized due to the lack of probes suitable for MAO-B-specific detection in live cells/tissues. Here we report the first two-photon, small molecule fluorogenic probe (U1) that enables highly sensitive/specific and real-time imaging of endogenous MAO-B activities across biological samples. We also used U1 to confirm the reported inverse relationship between parkin and MAO-B in PD models. With no apparent toxicity, U1 may be used to monitor MAO-B activities in small animals during disease development. In clinical samples, we find elevated MAO-B activities only in B lymphocytes (not in fibroblasts), hinting that MAO-B activity in peripheral blood cells might be an accessible biomarker for rapid detection of PD. Our results provide important starting points for using small molecule imaging techniques to explore MAO-B at the organism level.

Chromatin structure of the LCR in the human β-globin locus transcribing the adult δ- and β-globin genes.

PubMed

Kim, Seoyeon; Kim, Yea Woon; Shim, Sung Han; Kim, Chul Geun; Kim, Aeri

2012-03-01

The β-like globin genes are transcribed in a developmental stage specific fashion in erythroid cells. The specific transcription of globin genes is conferred by the locus control region (LCR), but the chromatin structure of the LCR in the human adult β-globin locus transcribing the δ- and β-globin genes is not clear. Here, we employed hybrid MEL cells that contain a human chromosome 11. The δ- and β-globin genes were highly transcribed in hybrid MEL/ch11 cells after transcriptional induction. LCR HS3 and HS2 were strongly occupied by erythroid specific transcriptional activators and co-factors in the induced locus. These HSs, but not HS4 and HS1, were in close proximity with the active globin genes as revealed by high resolution 3C experiments. The active features at HS3 were markedly established after transcriptional induction, while HS2 was in a relatively active conformation before the induction. Unexpectedly, HS1 did not show notable active features except histone hyperacetylation. Taken together, the LCR of the human β-globin locus transcribing the adult δ- and β-globin genes has HS specific chromatin structure. The structure at each HS, which is different from the locus transcribing the fetal globin genes, might relate to its role in transcribing the adult genes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI.

PubMed

Radinsky, Olga; Edri, Avishay; Brusilovsky, Michael; Fedida-Metula, Shlomit; Sobarzo, Ariel; Gershoni-Yahalom, Orly; Lutwama, Julius; Dye, John; Lobel, Leslie; Porgador, Angel

2017-07-20

Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors' sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

Analysis of the key enzymes of butyric and acetic acid fermentation in biogas reactors

PubMed Central

Gabris, Christina; Bengelsdorf, Frank R; Dürre, Peter

2015-01-01

This study aimed at the investigation of the mechanisms of acidogenesis, which is a key process during anaerobic digestion. To expose possible bottlenecks, specific activities of the key enzymes of acidification, such as acetate kinase (Ack, 0.23–0.99 U mg−1 protein), butyrate kinase (Buk, < 0.03 U mg−1 protein) and butyryl-CoA:acetate-CoA transferase (But, 3.24–7.64 U mg−1 protein), were determined in cell free extracts of biogas reactor content from three different biogas reactors. Furthermore, the detection of Ack was successful via Western blot analysis. Quantification of corresponding functional genes encoding Buk (buk) and But (but) was not feasible, although an amplification was possible. Thus, phylogenetic trees were constructed based on respective gene fragments. Four new clades of possible butyrate-producing bacteria were postulated, as well as bacteria of the genera Roseburia or Clostridium identified. The low Buk activity was in contrast to the high specific But activity in the analysed samples. Butyrate formation via Buk activity does barely occur in the investigated biogas reactor. Specific enzyme activities (Ack, Buk and But) in samples drawn from three different biogas reactors correlated with ammonia and ammonium concentrations (NH3 and NH4+-N), and a negative dependency can be postulated. Thus, high concentrations of NH3 and NH4+-N may lead to a bottleneck in acidogenesis due to decreased specific acidogenic enzyme activities. PMID:26086956

Use of Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) to determine hepatic blood flow

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

Stadalnik, R.C.; Vera, D.R.; Woodle, E.S.

1984-01-01

Tc-NGA is a new liver radiopharmaceutical which binds to a hepatocyte-specific membrane receptor. Three characteristics of Tc-NGA can be exploited in the measurement of hepatic blood flow (HBF): 1) ability to alter the affinity of Tc-NGA for its receptor by changing the galactose: albumin ratio; 2) ability to achieve a high specific activity with Tc-99m labeling; and 3) ability to administer a high molar dose of Tc-NGA without physiologic side effects. In addition, kinetic modeling of Tc-NGA dynamic data can provide estimates of hepatic receptor concentration. In experimental studies in young pigs, HBF was determined using two techniques: 1) kineticmore » modeling of dynamic data using moderate affinity, low specific activity Tc-NGA (Group A, n=12); and 2) clearance (CL) technique using high affinity, high specific activity Tc-NGA (Group B, n=4). In both groups, HBF was determined simultaneously by continuous infusion of indocyanine green (CI-ICG) with hepatic vein sampling. Regression analysis of HBF measurements obtained with the Tc-NGA kinetic modeling technique and the CI-ICG technique (Group A) revealed good correlation between the two techniques (r=0.802, p=0.02). Similarly, HBF determination by the clearance technique (Group B) provided highly accurate measurements when compared to the CI-ICG technique. Hepatic blood flow measurements by the clearance technique (CL-NGA) fell within one standard deviation of the error associated with each CI-ICG HBF measurement (all CI-ICG standard deviations were less than 10%).« less

Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.

PubMed

Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

2015-11-01

Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity. However, the addition of the repeat (di-peptide) and the retro-repeat (di-retro-peptide) sequences highly improved cancer cell toxicity up to 100% at 20 μM peptide concentration. Compared to the complete parent sequence hLFcin the derivatives showed toxicity on the melanoma cell line A375 increased by 10-fold and on the glioblastoma cell line U-87mg by 2-3-fold. Reduced killing velocity, apoptotic blebbing, activation of caspase 3/7 and formation of apoptotic DNA fragments proved that the active and cancer selective peptides, e.g. R-DIM-P-LF11-322, trigger apoptosis, whereas highly active, though non-selective peptides, such as DIM-LF11-318 and RW-AH seem to kill rapidly via necrosis inducing membrane lyses. Structural studies revealed specific toxicity on cancer cells by peptide derivatives with loop structures, whereas non-specific peptides comprised α-helical structures without loop. Model studies with the cancer membrane mimic phosphatidylserine (PS) gave strong evidence that PS only exposed by cancer cells is an important target for specific hLFcin derivatives. Other negatively charged membrane exposed molecules as sialic acid, heparan and chondroitin sulfate were shown to have minor impact on peptide activity. Copyright © 2015. Published by Elsevier B.V.

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

PubMed

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

2007-05-01

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

Nitrogen-enriched hierarchically porous carbons prepared from polybenzoxazine for high-performance supercapacitors.

PubMed

Wan, Liu; Wang, Jianlong; Xie, Lijing; Sun, Yahui; Li, Kaixi

2014-09-10

Nitrogen-enriched hierarchically porous carbons (HPCs) were synthesized from a novel nitrile-functionalized benzoxazine based on benzoxazine chemistry using a soft-templating method and a potassium hydroxide (KOH) chemical activation method and used as electrode materials for supercapacitors. The textural and chemical properties could be easily tuned by adding a soft template and changing the activation temperature. The introduction of the soft-templating agent (surfactant F127) resulted in the formation of mesopores, which facilitated fast ionic diffusion and reduced the internal resistance. The micropores of HPCs were extensively developed by KOH activation to provide large electrochemical double-layer capacitance. As the activation temperature increased from 600 to 800 °C, the specific surface area of nitrogen-enriched carbons increased dramatically, micropores were enlarged, and more meso/macropores were developed, but the nitrogen and oxygen content decreased, which affected the electrochemical performance. The sample HPC-800 activated at 800 °C possesses a high specific surface area (1555.4 m(2) g(-1)), high oxygen (10.61 wt %) and nitrogen (3.64 wt %) contents, a hierarchical pore structure, a high graphitization degree, and good electrical conductivity. It shows great pseudocapacitance and the largest specific capacitance of 641.6 F g(-1) at a current density of 1 A g(-1) in a 6 mol L(-1) KOH aqueous electrolyte when measured in a three-electrode system. Furthermore, the HPC-800 electrode exhibits excellent rate capability (443.0 F g(-1) remained at 40 A g(-1)) and good cycling stability (94.3% capacitance retention over 5000 cycles).

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

PubMed

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

2012-01-01

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

The RclR Protein Is a Reactive Chlorine-specific Transcription Factor in Escherichia coli *

PubMed Central

Parker, Benjamin W.; Schwessinger, Emily A.; Jakob, Ursula; Gray, Michael J.

2013-01-01

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance. PMID:24078635

The RclR protein is a reactive chlorine-specific transcription factor in Escherichia coli.

PubMed

Parker, Benjamin W; Schwessinger, Emily A; Jakob, Ursula; Gray, Michael J

2013-11-08

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance.

Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

DTIC Science & Technology

2015-07-01

describe: 1) major activities ; 2) specific objectives; 3) significant results or key outcomes, including major findings, developments, or conclusions...project progresses to completion, the emphasis in reporting in this section should shift from reporting activities to reporting accomplishments. B...high-resolution axial (depth) imaging as well. Of course, both techniques are under active development, and their properties may change sub

A high-throughput screen of the GTPase activity of Escherichia coli EngA to find an inhibitor of bacterial ribosome biogenesis

PubMed Central

Bharat, Amrita; Blanchard, Jan E.; Brown, Eric D.

2014-01-01

The synthesis of ribosomes is an essential process, which is aided by a variety of transacting factors in bacteria. Among these is a group of GTPases essential for bacterial viability and emerging as promising targets for new antibacterial agents. Herein, we describe a robust high-throughput screening process for inhibitors of one such GTPase, the Escherichia coli EngA protein. The primary screen employed an assay of phosphate production in 384-well density. Reaction conditions were chosen to maximize sensitivity for the discovery of competitive inhibitors while maintaining a strong signal amplitude and low noise. In a pilot screen of 31,800 chemical compounds, 44 active compounds were identified. Further, we describe the elimination of non-specific inhibitors that were detergent-sensitive or reactive as well as those that interfered with the high-throughput phosphate assay. Four inhibitors survived these common counter-screens for non-specificity but these chemicals were also inhibitors of the unrelated enzyme dihydrofolate reductase, suggesting that they too were promiscuously active. The high-throughput screen of the EngA protein described here provides a meticulous pilot study in the search for specific inhibitors of GTPases involved in ribosome biogenesis. PMID:23606650

Onion-derived N, S self-doped carbon materials as highly efficient metal-free electrocatalysts for the oxygen reduction reaction

NASA Astrophysics Data System (ADS)

Yang, Shuting; Mao, Xinxin; Cao, Zhaoxia; Yin, Yanhong; Wang, Zhichao; Shi, Mengjiao; Dong, Hongyu

2018-01-01

Onion-derived nitrogen, sulfur self-doped nanoporous carbon spheres (NSC) as efficient metal-free electrocatalyst were synthesized via a facile hydrothermal and subsequent pyrolysis process. The typical NSC with a high BET specific surface area of 1558 m2 g-1, contains 6.23 at.% N and 0.36 at.% S, and possesses high concentration of pyridinic and graphitic nitrogen species. Experimentally, the best performance was the NSC-A2 which showed excellent catalytic activity to oxygen reduction reaction via a 4 electron mechanism with an onset potential of 0.88 V (vs. RHE), and a superior stability comparable to commercial Pt/C catalyst. The high electrocatalytic activity is attributed to not only the synergistic effect of N and S dual doping in carbon and the sufficient active sites, but also its high BET specific surface area and suitable microporous structure. The results demonstrate that it is a simple and scalable approach for preparing efficient and low-cost carbon-based electrocatalysts for oxygen reduction reaction.

Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study.

PubMed

Sergutina, A V; Rakhmanova, V I

2016-06-01

Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter "monoamine oxidase activity", in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats.

Digital micromirror based near-infrared illumination system for plasmonic photothermal neuromodulation.

PubMed

Jung, Hyunjun; Kang, Hongki; Nam, Yoonkey

2017-06-01

Light-mediated neuromodulation techniques provide great advantages to investigate neuroscience due to its high spatial and temporal resolution. To generate a spatial pattern of neural activity, it is necessary to develop a system for patterned-light illumination to a specific area. Digital micromirror device (DMD) based patterned illumination system have been used for neuromodulation due to its simple configuration and design flexibility. In this paper, we developed a patterned near-infrared (NIR) illumination system for region specific photothermal manipulation of neural activity using NIR-sensitive plasmonic gold nanorods (GNRs). The proposed system had high power transmission efficiency for delivering power density up to 19 W/mm 2 . We used a GNR-coated microelectrode array (MEA) to perform biological experiments using E18 rat hippocampal neurons and showed that it was possible to inhibit neural spiking activity of specific area in neural circuits with the patterned NIR illumination. This patterned NIR illumination system can serve as a promising neuromodulation tool to investigate neuroscience in a wide range of physiological and clinical applications.

Two tobacco AP1-like gene promoters with highly specific, tightly regulated and uniquely expressed activity during floral transition, initiation and development

USDA-ARS?s Scientific Manuscript database

Biotech engineering of agronomic traits requires an array of highly specific and tightly regulated promoters in flower or other tissues. In this study, we isolated and characterized two tobacco AP1-like promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using GUS reporter and tissue-speci...

Silica decorated on porous activated carbon nanofiber composites for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Kim, So Yeun; Kim, Bo-Hye

2016-10-01

A hybrid of silica decorated on porous activated carbon nanofibers (ACNFs) is fabricated in the form of a web via electrospinning and an activation process as an electrode material for electrochemical capacitors in an organic electrolyte. The introduction of PhSiH3 (PS) into the polyacrylonitrile (PAN) solution induces a porous ACNF structure containing silica nanoparticles (NPs) via the spontaneous sol-gel process of PS by steam in the subsequent physical activation process. These inorganic-organic hybrid composites of porous ACNF containing silica NPs show superior specific capacitance and energy density in electrochemical tests, along with good rate capability and excellent cycle life in an organic electrolyte, which is attributed to the combination of ACNF's high surface area and silica's hydrophilicity. The electrochemical performance decreases with increasing PS concentration, and this trend is consistent with the specific surface area results, which reveal the rapid formation of a double layer.

Screening glycosynthase libraries with a fluoride chemosensor assay independently of enzyme specificity: identification of a transitional hydrolase to synthase mutant.

PubMed

Andrés, Eduardo; Aragunde, Hugo; Planas, Antoni

2014-03-01

Glycosynthases have become efficient tools for the enzymatic synthesis of oligosaccharides, glycoconjugates and polysaccharides. Enzyme-directed evolution approaches are applied to improve the performance of current glycosynthases and engineer specificity for non-natural substrates. However, simple and general screening methods are required since most of the reported assays are specific for each particular enzyme. In the present paper, we report a general screening assay that is independent of enzyme specificity, and implemented in an HTS (high-throughput screening) format for the screening of cell extracts in directed evolution experiments. Fluoride ion is a general by-product released in all glycosynthase reactions with glycosyl fluoride donors. The new assay is based on the use of a specific chemical sensor (a silyl ether of a fluorogenic methylumbelliferone) to transduce fluoride concentration into a fluorescence signal. As a proof-of-concept, it has been applied to a nucleophile saturation mutant library of Bacillus licheniformis 1,3-1,4-β-glucanase. Beyond the expected mutations at the glutamic acid (catalytic) nucleophile, other variants have been shown to acquire glycosynthase activity. Surprisingly, an aspartic acid for glutamic acid replacement renders a highly active glycosynthase, but still retains low hydrolase activity. It appears as an intermediate state between glycosyl hydrolase and glycosynthase.

Crystal structures of 3-methyladenine DNA glycosylase MagIII and the recognition of alkylated bases

PubMed Central

Eichman, Brandt F.; O’Rourke, Eyleen J.; Radicella, J.Pablo; Ellenberger, Tom

2003-01-01

DNA glycosylases catalyze the excision of chemically modified bases from DNA. Although most glycosylases are specific to a particular base, the 3-methyladenine (m3A) DNA glycosylases include both highly specific enzymes acting on a single modified base, and enzymes with broader specificity for alkylation-damaged DNA. Our structural understanding of these different enzymatic specificities is currently limited to crystal and NMR structures of the unliganded enzymes and complexes with abasic DNA inhibitors. Presented here are high-resolution crystal structures of the m3A DNA glycosylase from Helicobacter pylori (MagIII) in the unliganded form and bound to alkylated bases 3,9-dimethyladenine and 1,N6-ethenoadenine. These are the first structures of a nucleobase bound in the active site of a m3A glycosylase belonging to the helix–hairpin–helix superfamily. MagIII achieves its specificity for positively-charged m3A not by direct interactions with purine or methyl substituent atoms, but rather by stacking the base between two aromatic side chains in a pocket that excludes 7-methylguanine. We report base excision and DNA binding activities of MagIII active site mutants, together with a structural comparison of the HhH glycosylases. PMID:14517230

Australia's regional innovation systems: inter-industry interaction in innovative activities in three Australian territories

PubMed Central

Schütz, Marlies H.

2017-01-01

ABSTRACT Regional specifics reveal in differences in economic activity and structure, the institutional, socio-economic and cultural environment and not least in the capability of regions to create new knowledge and to generate innovations. Focusing on the regional level, this paper for three Australian territories (New South Wales, Victoria and Queensland) explores patterns of innovative activities in their private business sectors. Furthermore, these patterns are compared to specifics of each region's economic structure. We make use of input–output-based innovation flow networks, which are directed and weighted instead of binary. The value added of the proposed analysis is that we are able to trace a variety of different aspects related to the structure of innovative activities for each territory. It gets evident that mostly innovative activities in each territory are not strong in ‘niche’ branches but in fields of intense economic activity, signalising the high path-dependency of innovative activities in a specific geographical environment. PMID:29097849

Australia's regional innovation systems: inter-industry interaction in innovative activities in three Australian territories.

PubMed

Schütz, Marlies H

2017-07-03

Regional specifics reveal in differences in economic activity and structure, the institutional, socio-economic and cultural environment and not least in the capability of regions to create new knowledge and to generate innovations. Focusing on the regional level, this paper for three Australian territories (New South Wales, Victoria and Queensland) explores patterns of innovative activities in their private business sectors. Furthermore, these patterns are compared to specifics of each region's economic structure. We make use of input-output-based innovation flow networks, which are directed and weighted instead of binary. The value added of the proposed analysis is that we are able to trace a variety of different aspects related to the structure of innovative activities for each territory. It gets evident that mostly innovative activities in each territory are not strong in 'niche' branches but in fields of intense economic activity, signalising the high path-dependency of innovative activities in a specific geographical environment.

Beta-globin locus activation regions: conservation of organization, structure, and function.

PubMed Central

Li, Q L; Zhou, B; Powers, P; Enver, T; Stamatoyannopoulos, G

1990-01-01

The human beta-globin locus activation region (LAR) comprises four erythroid-specific DNase I hypersensitive sites (I-IV) thought to be largely responsible for activating the beta-globin domain and facilitating high-level erythroid-specific globin gene expression. We identified the goat beta-globin LAR, determined 10.2 kilobases of its sequence, and demonstrated its function in transgenic mice. The human and goat LARs share 6.5 kilobases of homologous sequences that are as highly conserved as the epsilon-globin gene promoters. Furthermore, the overall spatial organization of the two LARs has been conserved. These results suggest that the functionally relevant regions of the LAR are large and that in addition to their primary structure, the spatial relationship of the conserved elements is important for LAR function. Images PMID:2236034

JT9D-70/59 Improved High Pressure Turbine Active Clearance Control System. [for specific fuel consumption improvement

NASA Technical Reports Server (NTRS)

Gaffin, W. O.

1979-01-01

The JT9D-70/59 high pressure turbine active clearance control system was modified to provide reduction of blade tip clearance when the system is activated during cruise operation. The modification increased the flow capacity and air impingement effectiveness of the cooling air manifold to augment turbine case shrinkage capability, and increased responsiveness of the airseal clearance to case shrinkage. The simulated altitude engine testing indicated a significant improvement in specific fuel consumption with the modified system. A 1000 cycle engine endurance test showed no unusual wear or performance deterioration effects on the engine or the clearance control system. Rig tests indicated that the air impingement and seal support configurations used in the engine tests are near optimum.

Visible light-induced degradation of acetone over SO42-/MoOx/MgF2 catalysts.

PubMed

He, Yiming; Sheng, Tianlu; Wu, Ying; Chen, Jianshan; Fu, Ruibiao; Hu, Shengming; Wu, Xintao

2009-08-30

A visible light active photodegration catalyst was prepared by doping MoO(3) into MgF(2) matrix. The addition of SO(4)(2-) into MoO(x)/MgF(2) could improve the catalytic activity greatly and an acetone conversion of 96.1% under visible light was obtained on the SO(4)(2-)/5%MoO(x)/MgF(2) (SMM) catalyst. By BET, XRD, Raman, FT-IR, XPS, UV-vis technology the specific area, structure and photoadsorption ability of the catalysts were characterized. The high photocatlaytic activity of the SMM catalyst is attributed to its large specific area, the high dispersal of MoO(3) domains in MgF(2) and the inhibiting effect of MgF(2) matrix on the electron-hole pair recombination.

Protease-mediated drug delivery

NASA Astrophysics Data System (ADS)

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

2003-12-01

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

Utilizing high-throughput bioassays associated with US EPA ToxCast Program to assess biological activity of environmental contaminants: A case study of chemical mixtures

EPA Science Inventory

Effects-based monitoring and surveillance is increasingly being utilized in conjunction with chemical monitoring to determine potential biological activity associated with environmental contaminants. Supervised approaches targeting specific chemical activity or molecular pathways...

Continuous High Frequency Activity: A peculiar SEEG pattern related to specific brain regions

PubMed Central

Melani, Federico; Zelmann, Rina; Mari, Francesco; Gotman, Jean

2015-01-01

Objective While visually marking the high frequency oscillations in the stereo-EEG of epileptic patients, we observed a continuous/semicontinuous activity in the ripple band (80–250 Hz), which we defined continuous High Frequency Activity (HFA). We aim to analyze in all brain regions the occurrence and significance of this particular pattern. Methods Twenty patients implanted in mesial temporal and neocortical areas were studied. One minute of slow-wave sleep was reviewed. The background was classified as continuous/semicontinuous, irregular, or sporadic based on the duration of the fast oscillations. Each channel was classified as inside/outside the seizure onset zone (SOZ) or a lesion. Results The continuous/semicontinuous HFA occurred in 54 of the 790 channels analyzed, with a clearly higher prevalence in hippocampus and occipital lobe. No correlation was found with the SOZ or lesions. In the occipital lobe the continuous/semicontinuous HFA was present independently of whether eyes were open or closed. Conclusions We describe what appears to be a new physiological High Frequency Activity, independent of epileptogenicity, present almost exclusively in the hippocampus and occipital cortex but independent of the alpha rhythm. Significance The continuous HFA may be an intrinsic characteristic of specific brain regions, reflecting a particular type of physiological neuronal activity. PMID:23768436

Visual Contrast Sensitivity Improvement by Right Frontal High-Beta Activity Is Mediated by Contrast Gain Mechanisms and Influenced by Fronto-Parietal White Matter Microstructure

PubMed Central

Quentin, Romain; Elkin Frankston, Seth; Vernet, Marine; Toba, Monica N.; Bartolomeo, Paolo; Chanes, Lorena; Valero-Cabré, Antoni

2016-01-01

Behavioral and electrophysiological studies in humans and non-human primates have correlated frontal high-beta activity with the orienting of endogenous attention and shown the ability of the latter function to modulate visual performance. We here combined rhythmic transcranial magnetic stimulation (TMS) and diffusion imaging to study the relation between frontal oscillatory activity and visual performance, and we associated these phenomena to a specific set of white matter pathways that in humans subtend attentional processes. High-beta rhythmic activity on the right frontal eye field (FEF) was induced with TMS and its causal effects on a contrast sensitivity function were recorded to explore its ability to improve visual detection performance across different stimulus contrast levels. Our results show that frequency-specific activity patterns engaged in the right FEF have the ability to induce a leftward shift of the psychometric function. This increase in visual performance across different levels of stimulus contrast is likely mediated by a contrast gain mechanism. Interestingly, microstructural measures of white matter connectivity suggest a strong implication of right fronto-parietal connectivity linking the FEF and the intraparietal sulcus in propagating high-beta rhythmic signals across brain networks and subtending top-down frontal influences on visual performance. PMID:25899709

AFRRI Reports, Second Quarter 1994

DTIC Science & Technology

1994-08-01

the antrum wete immediately placed in sterile 0.9% NaCl, kept on ice, coded, and then prepared for culture, smears, and urease assay by homogeniza...high urease specific activity (>1 |J.mol- min-1 ■ mg protein-1) plus high-affinity substrate binding (Mi- chaelis constant [K^\\ < 1 mmol/L),27 in at...031, respectively), and the characteristic bacterial growth with high-activity product.on of a urease with tight substrate binding " was found in

Association between sedentary behavior, physical activity, and obesity: inactivity among active kids.

PubMed

Wong, Suzy L; Leatherdale, Scott T

2009-01-01

Sedentary behavior and physical activity are not mutually exclusive behaviors. The relative risk of overweight for adolescents who are highly sedentary and highly physically active is unclear. A better understanding of the relationship between sedentary behaviors, physical activity, and body mass index (BMI) would provide insight for developing interventions to prevent or reduce overweight. Using the physical activity module of the School Health Action, Planning and Evaluation System (SHAPES), we collected data from 25,060 students in grades 9 through 12 from 76 secondary schools in Ontario, Canada. Sex-specific logistic regression analyses were performed to examine how BMI, weight perceptions, social influences, team sports participation, and smoking behavior were associated with being 1) high active-high sedentary, 2) low active-low sedentary, and 3) low active-high sedentary. Low active-high sedentary boys were more likely to be overweight than high active-low sedentary boys (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.01-2.58). When compared with high active-low sedentary girls, girls who were low active-high sedentary (OR, 2.24; 95% CI, 1.23-4.09) or high active-high sedentary (OR, 1.91; 95% CI, 1.01-3.61) were more likely to be overweight. Sedentary behavior may moderate the relationship between physical activity and overweight. Developing a better understanding of sedentary behavior in relation to physical activity and overweight is critical for preventing and reducing overweight among youth.

The activity of nitrifying microorganisms in a high-altitude Andean wetland.

PubMed

Molina, Verónica; Dorador, Cristina; Fernández, Camila; Bristow, Laura; Eissler, Yoanna; Hengst, Martha; Hernandez, Klaudia; Olsen, Lasse Mork; Harrod, Chris; Marchant, Francisca; Anguita, Cristobal; Cornejo, Marcela

2018-06-01

High-altitude wetland holds freshwater springs, evaporitic ponds and lagoon with variable salinity and nutrients, potentially influencing the ecology of nitrifying communities. In this study, nitrifying microorganisms in Salar de Huasco (Chile) were surveyed to determine bacterial and archaeal contribution to ammonium (AO), nitrite oxidation (NO), ammonium uptake (AU) during wet and dry seasons. The activity signals from these groups were assessed by specific amoA-qPCR transcription, 15N tracer studies and addition of group specific inhibitor experiments for nitrifying microorganisms (N1-guanyl-1, 7-diaminoheptane [GC7]-archaeal specific and allylthiourea [ATU]-bacterial specific). Nitrifying communities, i.e. Nitrosopumilus, Nitrosospira, Nitrosomonas, Kuenenia and Nitrospira, were more frequent (∼0.25% of 16S rRNA sequences) at low salinity sites. Bacterial amoA-qPCR transcripts also increased at low salinity and along in situ ammonium increase observed between wet/dry seasons. Nutrient changes through time and 15N tracer experiments results showed that AO and NO were detected and peaked mainly at low salinity-high ammonium sites (<37 000 μS cm-1 and >0.3 μM), whereas AU was predominant at evaporitic sites. Our results indicate that salinity and ammonium affect the nitrifying communities that are potentially more active at low-salinity sites but persistent at saltier evaporitic areas of the wetland when ammonium is available.

Graphing Calculators, the CBL2[TM] and TI-Interactive[TM] in High School Science.

ERIC Educational Resources Information Center

Molnar, Bill

This collection of activities is designed to show how TI-Interactive[TM] and Calculator-based Laboratories (CBL) can be used to explore topics in high school science. The activities address such topics as specific heat, Boyle's Law, Newton's Law of Cooling, and Antarctic Ozone Levels. Teaching notes and calculator instructions are included as are…

Relationships between sucretolerance and salinotolerance in bacteria from hypersaline environments and their implications for the exploration of Mars and the icy worlds

NASA Astrophysics Data System (ADS)

Fredsgaard, Casper; Moore, Donald B.; Al Soudi, Amer F.; Crisler, James D.; Chen, Fei; Clark, Benton C.; Schneegurt, Mark A.

2017-04-01

The most extremely osmotolerant microbial isolates are fungi from high-sugar environments that tolerate the lowest water activity (0.61) for growth yet reported. Studies of osmotolerant bacteria have focused on halotolerance rather than sucretolerance (ability to grow in high sugar concentrations). A collection of salinotolerant (>=10% NaCl or >=50% MgSO4) bacterial isolates from the Great Salt Plains of Oklahoma and Hot Lake in Washington were screened for sucretolerance in medium supplemented with >=50% fructose, glucose or sucrose. Tolerances significantly differed between solutes, even though water activities for saline media (0.92 and 0.85 for 10 and 20% NaCl Salt Plains media, respectively) were comparable or lower than water activities for high-sugar media (0.93 and 0.90 for 50 and 70% sucrose artificial nectar media, respectively). These specific solute effects were differentially expressed among individual isolates. Extrapolating the results of earlier food science studies with yeasts at high sugar concentrations to bacteria in salty environments with low water activity should be done with caution. Furthermore, the discussion of habitable Special Regions on Mars and the icy worlds should reflect an understanding of specific solute effects.

A New Versatile Microarray-based Method for High Throughput Screening of Carbohydrate-active Enzymes*

PubMed Central

Vidal-Melgosa, Silvia; Pedersen, Henriette L.; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B.; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G. T.

2015-01-01

Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths. PMID:25657012

Salt melt synthesis of curved nitrogen-doped carbon nanostructures: ORR kinetics boost

NASA Astrophysics Data System (ADS)

Rybarczyk, Maria K.; Gontarek, Emilia; Lieder, Marek; Titirici, Maria-Magdalena

2018-03-01

Implementing metal-free electrocatalysts for the oxygen reduction reaction (ORR) and revealing crucial chemical or topographical parameters driving their activity are vital for the development of power cells. The carbon-based catalysts are very often synthesized through carbonization of biopolymers, in particular, those one containing nitrogen groups such as chitosan. Unfortunately, the resulting carbonaceous materials usually lack specific porosity and exhibit low catalytic activity. Here, we demonstrate that pyrolysis of chitosan in a ZnCl2 melt assisted by the presence of LiCl results not only in a highly porous activated carbon material with a specific surface area of 1317.97 m2/g and the total nitrogen content of 6.5%, but also induces unexpected curvature in the grown graphitic layers. This is the first work that shows curved graphene layers obtained from a biopolymer precursor by its pyrolytic decomposition in the melted salt media. On the other hand, a carbonaceous material obtained from chitosan but without the salts has very low specific surface area of 7.8 m2/g, possesses no specific structural features, and contains 4.7% of nitrogen. The electrochemical studies show, that the former material is highly active towards four-electron pathway of the ORR in terms of an onset potential (0.89 V vs RHE) and the turnover frequency (TOFmax = 0.095 e site-1 s-1). We attribute this high catalytic performance to the presence of the pyridinic and pyrrolic sites in the structure. The ORR kinetics is probably further promoted by curvature in the graphitic layers.

Peroxisome Proliferator-Activated Receptor Subtype- and Cell-Type-Specific Activation of Genomic Target Genes upon Adenoviral Transgene Delivery

PubMed Central

Nielsen, Ronni; Grøntved, Lars; Stunnenberg, Hendrik G.; Mandrup, Susanne

2006-01-01

Investigations of the molecular events involved in activation of genomic target genes by peroxisome proliferator-activated receptors (PPARs) have been hampered by the inability to establish a clean on/off state of the receptor in living cells. Here we show that the combination of adenoviral delivery and chromatin immunoprecipitation (ChIP) is ideal for dissecting these mechanisms. Adenoviral delivery of PPARs leads to a rapid and synchronous expression of the PPAR subtypes, establishment of transcriptional active complexes at genomic loci, and immediate activation of even silent target genes. We demonstrate that PPARγ2 possesses considerable ligand-dependent as well as independent transactivation potential and that agonists increase the occupancy of PPARγ2/retinoid X receptor at PPAR response elements. Intriguingly, by direct comparison of the PPARs (α, γ, and β/δ), we show that the subtypes have very different abilities to gain access to target sites and that in general the genomic occupancy correlates with the ability to activate the corresponding target gene. In addition, the specificity and potency of activation by PPAR subtypes are highly dependent on the cell type. Thus, PPAR subtype-specific activation of genomic target genes involves an intricate interplay between the properties of the subtype- and cell-type-specific settings at the individual target loci. PMID:16847324

Intrinsic activation: the relationship between biomass inorganic content and porosity formation during pyrolysis.

PubMed

Stratford, James P; Hutchings, Tony R; de Leij, Frans A A M

2014-05-01

The utility of pyrolytic carbons is closely related to their porosity and surface area, there is a clear benefit to the development of biomass pyrolysis processes which produce highly porous carbons. The results presented in this work demonstrate that by using biomass precursors with high inorganic content along with specified process conditions, carbons can be consistently produced with specific surface areas between 900 and 1600 m(2)/g. Results from 12 different source materials show that the formation of increased porosity in pyrolytic carbons is strongly associated with the presence of inorganic elements in the precursors including: magnesium, potassium and sulfur. It was found that pyrolysis of macro-algae can produce especially high specific surface area carbons (mean: 1500 m(2)/g), without externally applied activating agents. Using cheap readily available agricultural residues such as oilseed rape straw, pyrolytic carbons can be produced with specific surface areas of around 950 m(2)/g. Copyright © 2014 Elsevier Ltd. All rights reserved.

A high-capacity carbon prepared from renewable chicken feather biopolymer for supercapacitors

NASA Astrophysics Data System (ADS)

Wang, Qiang; Cao, Qi; Wang, Xianyou; Jing, Bo; Kuang, Hao; Zhou, Ling

2013-03-01

Micropopous chicken feather carbon (CFC) severing as electrode materials for the first time is prepared via the activation with KOH agent to different extents. The structure and electrochemical properties of CFC materials are characterized with N2 adsorption/desorption measurements, X-ray diffraction (XRD), transmission electron microscope (TEM), cyclic voltammetry (CV), galvanostatic charge/discharge cycling and electrochemical impedance spectroscopy (EIS). The obtained results show that CFC activated by KOH with KOH/CFC weight ratio of 4/1 (CFCA4) possesses the specific surface area of 1839 m2 g-1, average micropore diameter of 1.863 nm, and exhibits the highest initial specific capacitance of 302 F g-1 at current density of 1 A g-1 in 1 M H2SO4, and that even after 5000 cycles, CFCA4 specific capacitance is still as high as 253 F g-1. Furthermore, CFCA4 also delivers specific capacitance of 181 F g-1 at current density of 5 A g-1 and 168 F g-1 at current density of 10 A g-1. Accordingly, the microporous activated carbon material derived from chicken feather provides favorable prospect in electrode materials application in supercapacitors.

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity.

PubMed

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-29

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity

NASA Astrophysics Data System (ADS)

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-01

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

KDM1 Class Flavin-Dependent Protein Lysine Demethylases

PubMed Central

Burg, Jonathan M.; Link, Jennifer E.; Morgan, Brittany S.; Heller, Frederick J.; Hargrove, Amanda E.; McCafferty, Dewey G.

2015-01-01

Flavin-dependent, lysine-specific protein demethylases (KDM1s) are a subfamily of amine oxidases that catalyze the selective posttranslational oxidative demethylation of methyllysine side chains within protein and peptide substrates. KDM1s participate in the widespread epigenetic regulation of both normal and disease state transcriptional programs. Their activities are central to various cellular functions, such as hematopoietic and neuronal differentiation, cancer proliferation and metastasis, and viral lytic replication and establishment of latency. Interestingly, KDM1s function as catalytic subunits within complexes with coregulatory molecules that modulate enzymatic activity of the demethylases and coordinate their access to specific substrates at distinct sites within the cell and chromatin. Although several classes of KDM1 -selective small molecule inhibitors have been recently developed, these pan-active site inhibition strategies lack the ability to selectively discriminate between KDM1 activity in specific, and occasionally opposing, functional contexts within these complexes. Here we review the discovery of this class of demethylases, their structures, chemical mechanisms, and specificity. Additionally, we review inhibition of this class of enzymes as well as emerging interactions with coregulatory molecules that regulate demethylase activity in highly specific functional contexts of biological and potential therapeutic importance. PMID:25787087

Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

PubMed Central

Dieker, Jürgen; Berden, Jo H.; Bakker, Marinka; Briand, Jean-Paul; Muller, Sylviane; Voll, Reinhard; Sjöwall, Christopher; Herrmann, Martin; Hilbrands, Luuk B.; van der Vlag, Johan

2016-01-01

Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis. PMID:27780265

Peroxide-assisted microwave activation of pyrolysis char for adsorption of dyes from wastewater.

PubMed

Nair, Vaishakh; Vinu, R

2016-09-01

In this study, mesoporous activated biochar with high surface area and controlled pore size was prepared from char obtained as a by-product of pyrolysis of Prosopis juliflora biomass. The activation was carried out by a simple process that involved H2O2 treatment followed by microwave pyrolysis. H2O2 impregnation time and microwave power were optimized to obtain biochar with high specific surface area and high adsorption capacity for commercial dyes such as Remazol Brilliant Blue and Methylene Blue. Adsorption parameters such as initial pH of the dye solution and adsorbent dosage were also optimized. Pore size distribution, surface morphology and elemental composition of activated biochar were thoroughly characterized. H2O2 impregnation time of 24h and microwave power of 600W produced nanostructured biochar with narrow and deep pores of 357m(2)g(-1) specific surface area. Langmuir and Langmuir-Freundlich isotherms described the adsorption equilibrium, while pseudo second order model described the kinetics of adsorption. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA.

PubMed

Herzner, Anna-Maria; Hagmann, Cristina Amparo; Goldeck, Marion; Wolter, Steven; Kübler, Kirsten; Wittmann, Sabine; Gramberg, Thomas; Andreeva, Liudmila; Hopfner, Karl-Peter; Mertens, Christina; Zillinger, Thomas; Jin, Tengchuan; Xiao, Tsan Sam; Bartok, Eva; Coch, Christoph; Ackermann, Damian; Hornung, Veit; Ludwig, Janos; Barchet, Winfried; Hartmann, Gunther; Schlee, Martin

2015-10-01

Cytosolic DNA that emerges during infection with a retrovirus or DNA virus triggers antiviral type I interferon responses. So far, only double-stranded DNA (dsDNA) over 40 base pairs (bp) in length has been considered immunostimulatory. Here we found that unpaired DNA nucleotides flanking short base-paired DNA stretches, as in stem-loop structures of single-stranded DNA (ssDNA) derived from human immunodeficiency virus type 1 (HIV-1), activated the type I interferon-inducing DNA sensor cGAS in a sequence-dependent manner. DNA structures containing unpaired guanosines flanking short (12- to 20-bp) dsDNA (Y-form DNA) were highly stimulatory and specifically enhanced the enzymatic activity of cGAS. Furthermore, we found that primary HIV-1 reverse transcripts represented the predominant viral cytosolic DNA species during early infection of macrophages and that these ssDNAs were highly immunostimulatory. Collectively, our study identifies unpaired guanosines in Y-form DNA as a highly active, minimal cGAS recognition motif that enables detection of HIV-1 ssDNA.

In vitro autoradiographic localization of angiotensin-converting enzyme in sarcoid lymph nodes

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

Allen, R.K.; Chai, S.Y.; Dunbar, M.S.

1986-09-01

Angiotensin-converting enzyme (ACE) was localized in sarcoid lymph nodes by an in vitro autoradiographic technique using a synthetic ACE inhibitor of high affinity, /sup 125/I-labelled 351A. The lymph nodes were from seven patients with active sarcoidosis who underwent mediastinoscopy and from six control subjects who had nodes resected at either mediastinoscopy or laparotomy. Angiotensin-converting enzyme was localized in the epithelioid cells of sarcoid granulomata in markedly increased amounts compared with control nodes, where it was restricted to vessels and some histiocytes. In sarcoid lymph nodes, there was little ACE present in lymphocytes or fibrous tissue. Sarcoid nodes with considerable fibrosismore » had much less intense ACE activity than the nonfibrotic nodes. The specific activity of ACE measured by an enzymatic assay in both the control and sarcoid lymph nodes closely reflected the ACE activity demonstrated by autoradiography. Sarcoid lymph nodes with fibrosis had an ACE specific activity of half that of nonfibrotic nodes (p less than 0.05). There was a 15-fold increase in specific ACE activity in sarcoid nodes (p less than 0.05) compared to normal. Serum ACE was significantly higher in those sarcoid patients whose lymph nodes were not fibrosed compared with those with fibrosis (p less than 0.01). This technique offers many advantages over the use of polyclonal antibodies. The 351A is a highly specific ACE inhibitor, chemically defined and in limitless supply. This method enables the quantitation of results, and autoradiographs may be stored indefinitely for later comparison.« less

The Diagnostic Role of Magnetic Resonance Enterography as a Complementary Test to Colonoscopy in Active Crohn's Disease.

PubMed

Aryan, Arvin; Azizi, Zahra; Teimouri, Azam; Ebrahimi Daryani, Nasser; Aletaha, Najme; Jahanbakhsh, Ali; Nouritaromlou, Mohammad Kazem; Alborzi, Forough; Mami, Masoud; Basirat, Vahid; Javid Anbardan, Sanam

2016-04-01

BACKGROUND According to recent studies comparing magnetic resonance enterography (MRE) with ileocolonoscopy for assessing inflammation of small bowel and colonic segments in adults with active Crohn's disease (CD), we aimed to compare the accuracy of these two diagnostic methods in Iranian population. METHODS During 2013-2014 a follow-up study was done on 30 patients with active CD in a gastroenterology clinic affiliated to Tehran University of Medical Sciences. MRE and ileocolonoscopy were performed for all the patients. All statistical analyses were performed using SPSS (version 18) and p-value<0.05 was considered as statistically significant. RESULTS Of the 30 patients with active CD, 11(36.7%) were men and 19 (63.3%) were women with mean age of 37.30±13.66 years (range: 19-67 years). MRE had sensitivity and specificity of 50% and 90% with positive predictive value (PPV) and negative predictive value (NPV) of 71.43 and 78.26, respectively for localizing sigmoid lesions and ileum had sensitivity and specificity of 84.21 and 45.45 with PPV and NPV of 72.73 and 62.50, respectively. CONCLUSION While moderate sensitivity and high specificity of MRE in localizing colonic lesions makes it an appropriate confirmatory test after colonoscopy, the reported high sensitivity and moderate specificity of MRE versus colonoscopy in detecting ileal lesions makes it a suitable screening test for ileal lesions. Finally we can conclude that MRE can be an important complementary test to colonoscopy in detecting active disease.

Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling.

PubMed Central

Janssens, V; Goris, J

2001-01-01

Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit, the activity of which is highly regulated. Regulation is accomplished mainly by members of a family of regulatory subunits, which determine the substrate specificity, (sub)cellular localization and catalytic activity of the PP2A holoenzymes. Moreover, the catalytic subunit is subject to two types of post-translational modification, phosphorylation and methylation, which are also thought to be important regulatory devices. The regulatory ability of PTPA (PTPase activator), originally identified as a protein stimulating the phosphotyrosine phosphatase activity of PP2A, will also be discussed, alongside the other regulatory inputs. The use of specific PP2A inhibitors and molecular genetics in yeast, Drosophila and mice has revealed roles for PP2A in cell cycle regulation, cell morphology and development. PP2A also plays a prominent role in the regulation of specific signal transduction cascades, as witnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular and viral proteins, which are PP2A substrates, target PP2A to different subcellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon. PMID:11171037

Agreement between BMI and body fat obesity definitions in a physically active population.

PubMed

Porto, Luiz Guilherme G; Nogueira, Rosenkranz M; Nogueira, Eugênio C; Molina, Guilherme E; Farioli, Andrea; Junqueira, Luiz Fernando; Kales, Stefanos N

2016-01-01

Body mass index (BMI) is a widely used proxy of body composition (BC). Concerns exist regarding possible BMI misclassification among active populations. We compared the prevalence of obesity as categorized by BMI or by skinfold estimates of body fat percentage (BF%) in a physically active population. 3,822 military firefighters underwent a physical fitness evaluation including cardiorespiratory fitness (CRF) by the 12 min-Cooper test, abdominal strength by sit-up test (SUT) and body composition (BC) by BF% (as the reference), as well as BMI. Obesity was defined by BF% > 25% and BMI ≥ 30 kg/m2. Agreement was evaluated by sensitivity and specificity of BMI, positive and negative predictive values (PPV/NPV), positive and negative likelihood (LR+/LR-), receiver operating characteristic (ROC) curves and also across age, CRF and SUT subgroups. The prevalence of obesity estimated by BMI (13.3%) was similar to BF% (15.9%). Overall agreement was high (85.8%) and varied in different subgroups (75.3-94.5%). BMI underestimated the prevalence of obesity in all categories with high specificity (≥ 81.2%) and low sensitivity (≤ 67.0). All indices were affected by CRF, age and SUT, with better sensitivity, NPV and LR- in the less fit and older groups; and higher specificity, PPV and LR+ among the fittest and youngest groups. ROC curves showed high area under the curve (≥ 0.77) except for subjects with CRF ≥ 14 METs (= 0.46). Both measures yielded similar obesity prevalences, with high agreement. BMI did not overestimate obesity prevalence. BMI ≥ 30 was highly specific to exclude obesity. Because of systematic under estimation, a lower BMI cut-off point might be considered in this population.

From rice bran to high energy density supercapacitors: a new route to control porous structure of 3D carbon.

PubMed

Hou, Jianhua; Cao, Chuanbao; Ma, Xilan; Idrees, Faryal; Xu, Bin; Hao, Xin; Lin, Wei

2014-12-01

Controlled micro/mesopores interconnected structures of three-dimensional (3D) carbon with high specific surface areas (SSA) are successfully prepared by carbonization and activation of biomass (raw rice brans) through KOH. The highest SSA of 2475 m(2) g(-1) with optimized pore volume of 1.21 cm(3) g(-1) (40% for mesopores) is achieved for KOH/RBC = 4 mass ratio, than others. The as-prepared 3D porous carbon-based electrode materials for supercapacitors exhibit high specific capacitance specifically at large current densities of 10 A g(-1) and 100 A g(-1) i.e., 265 F g(-1) and 182 F g(-1) in 6 M KOH electrolyte, respectively. Moreover, a high power density ca. 1223 W kg(-1) (550 W L(-1)) and energy density 70 W h kg(-1) (32 W h L(-1)) are achieved on the base of active material loading (~10 mg cm(2)) in the ionic liquid. The findings can open a new avenue to use abundant agricultural by-products as ideal materials with promising applications in high-performance energy-storage devices.

From Rice Bran to High Energy Density Supercapacitors: A New Route to Control Porous Structure of 3D Carbon

NASA Astrophysics Data System (ADS)

Hou, Jianhua; Cao, Chuanbao; Ma, Xilan; Idrees, Faryal; Xu, Bin; Hao, Xin; Lin, Wei

2014-12-01

Controlled micro/mesopores interconnected structures of three-dimensional (3D) carbon with high specific surface areas (SSA) are successfully prepared by carbonization and activation of biomass (raw rice brans) through KOH. The highest SSA of 2475 m2 g-1 with optimized pore volume of 1.21 cm3 g-1 (40% for mesopores) is achieved for KOH/RBC = 4 mass ratio, than others. The as-prepared 3D porous carbon-based electrode materials for supercapacitors exhibit high specific capacitance specifically at large current densities of 10 A g-1 and 100 A g-1 i.e., 265 F g-1 and 182 F g-1 in 6 M KOH electrolyte, respectively. Moreover, a high power density ca. 1223 W kg-1 (550 W L-1) and energy density 70 W h kg-1 (32 W h L-1) are achieved on the base of active material loading (~10 mg cm2) in the ionic liquid. The findings can open a new avenue to use abundant agricultural by-products as ideal materials with promising applications in high-performance energy-storage devices.

Facile synthesis of NiS anchored carbon nanofibers for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Xu, Jinling; Zhang, Li; Xu, Guancheng; Sun, Zhipeng; Zhang, Chi; Ma, Xin; Qi, Chunling; Zhang, Lu; Jia, Dianzeng

2018-03-01

Transition metal sulfide compounds with carbon materials are promising for high-performance supercapacitors. Carbon nanofibers (CNFs) wrapped with NiS nanoparticles were herein obtained through electrospinning and calcination. NiS nanoparticles in composite nanofibers are covered by a layer of graphitic carbon, which not only increase the conductivity but also provide active regions for nanoparticle growth to prevent aggregation. The CNFs-NiS electrode has high specific capacity of 177.1 mAh g-1 at 1 A g-1 (0.41 mAh cm-2 at a current density of 2.3 mA cm-2) and long-term cycling stability, with 88.7% capacitance retention after 5000 cycles. The excellent electrochemical activity may be attributed to the accessible specific surface, unique porous structure of CNFs and high specific capacitance of NiS. In addition, the asymmetric supercapacitor has an enhanced volumetric energy density of 13.32 mWh cm-3 at a volumetric power density of 180 mW cm-3 and high cycling stability, with 89.5% capacitance retention after 5000 cycles. It also successfully lights up a light-emitting diode. The CNFs-NiS composite has significant potential applications in supercapacitor.

From Rice Bran to High Energy Density Supercapacitors: A New Route to Control Porous Structure of 3D Carbon

PubMed Central

Hou, Jianhua; Cao, Chuanbao; Ma, Xilan; Idrees, Faryal; Xu, Bin; Hao, Xin; Lin, Wei

2014-01-01

Controlled micro/mesopores interconnected structures of three-dimensional (3D) carbon with high specific surface areas (SSA) are successfully prepared by carbonization and activation of biomass (raw rice brans) through KOH. The highest SSA of 2475 m2 g−1 with optimized pore volume of 1.21 cm3 g−1 (40% for mesopores) is achieved for KOH/RBC = 4 mass ratio, than others. The as-prepared 3D porous carbon-based electrode materials for supercapacitors exhibit high specific capacitance specifically at large current densities of 10 A g−1 and 100 A g−1 i.e., 265 F g−1 and 182 F g−1 in 6 M KOH electrolyte, respectively. Moreover, a high power density ca. 1223 W kg−1 (550 W L−1) and energy density 70 W h kg−1 (32 W h L−1) are achieved on the base of active material loading (~10 mg cm2) in the ionic liquid. The findings can open a new avenue to use abundant agricultural by-products as ideal materials with promising applications in high-performance energy-storage devices. PMID:25434348

Stereotypic wheel running decreases cortical activity in mice

PubMed Central

Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

2016-01-01

Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands.

PubMed

Salter, Jason D; Smith, Harold C

2018-05-23

The 11-member APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of zinc-dependent cytidine deaminases bind to RNA and single-stranded DNA (ssDNA) and, in specific contexts, modify select (deoxy)cytidines to (deoxy)uridines. In this review, we describe advances made through high-resolution co-crystal structures of APOBECs bound to mono- or oligonucleotides that reveal potential substrate-specific binding sites at the active site and non-sequence-specific nucleic acid binding sites distal to the active site. We also discuss the effect of APOBEC oligomerization on functionality. Future structural studies will need to address how ssDNA binding away from the active site may enhance catalysis and the mechanism by which RNA binding may modulate catalytic activity on ssDNA. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Purification and Kinetics of Higher Plant NADH:Nitrate Reductase.

PubMed

Campbell, W H; Smarrelli, J

1978-04-01

Squash cotyledon (Cucurbita pepo L.) NADH:nitrate reductase (NR) was purified 150-fold with 50% recovery by a single step procedure based on the affinity of the NR for blue-Sepharose. Blue-Sepharose, which is prepared by direct coupling of Cibacron blue to Sepharose, appears to bind squash NR at the NADH site. The NR can be purified in 2 to 3 hours to a specific activity of 2 mumol of NADH oxidized/minute * milligram of protein. Corn (Zea mays L.) leaf NR was also purified to a specific activity of 6.9 mumol of NADH oxidized/minute * milligram of protein using a blue-Sepharose affinity step. The blue-Sepharose method offers the advantages of a rapid purification of plant NR to a high specific activity with reasonable recovery of total activity.The kinetic mechanism of higher plant NR was investigated using these highly purified squash and corn NR preparations. Based on initial velocity and product inhibition studies utilizing both enzymes, a two-site ping-pong mechanism is proposed for NR. This kinetic mechanism incorporates the concept of the reduced NR transferring electrons from the NADH site to a physically separated nitrate site.

Optimization of extraction of novel pectinase enzyme discovered in red pitaya (Hylocereus polyrhizus) peel.

PubMed

Zohdi, Nor Khanani; Amid, Mehrnoush

2013-11-20

Plant peels could be a potential source of novel pectinases for use in various industrial applications due to their broad substrate specificity with high stability under extreme conditions. Therefore, the extraction conditions of a novel pectinase enzyme from pitaya peel was optimized in this study. The effect of extraction variables, namely buffer to sample ratio (2:1 to 8:1, X₁), extraction temperature (-15 to +25 °C, X₂) and buffer pH (4.0 to 12.0, X₃) on specific activity, temperature stability, storage stability and surfactant agent stability of pectinase from pitaya peel was investigated. The study demonstrated that the optimum conditions for the extraction of pectinase from pitaya sources could improve the enzymatic characteristics of the enzyme and protect its activity and stability during the extraction procedure. The optimum extraction conditions cause the pectinase to achieve high specific activity (15.31 U/mg), temperature stability (78%), storage stability (88%) and surfactant agent stability (83%). The most desirable conditions to achieve the highest activity and stability of pectinase enzyme from pitaya peel were the use of 5:1 buffer to sample ratio at 5 °C and pH 8.0.

Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions.

PubMed

Netto, Luis Eduardo S; de Oliveira, Marcos Antonio; Tairum, Carlos A; da Silva Neto, José Freire

2016-01-01

Thiol-disulfide exchange reactions are highly reversible, displaying nucleophilic substitutions mechanism (S(N)2 type). For aliphatic, low molecular thiols, these reactions are slow, but can attain million times faster rates in enzymatic processes. Thioredoxin (Trx) proteins were the first enzymes described to accelerate thiol-disulfide exchange reactions and their high reactivity is related to the high nucleophilicity of the attacking thiol. Substrate specificity in Trx is achieved by several factors, including polar, hydrophobic, and topological interactions through a groove in the active site. Glutaredoxin (Grx) enzymes also contain the Trx fold, but they do not share amino acid sequence similarity with Trx. A conserved glutathione binding site is a typical feature of Grx that can reduce substrates by two mechanisms (mono and dithiol). The high reactivity of Grx enzymes is related to the very acid pK(a) values of reactive Cys that plays roles as good leaving groups. Therefore, although distinct oxidoreductases catalyze similar thiol–disulfide exchange reactions, their enzymatic mechanisms vary. PDI and DsbA are two other oxidoreductases, but they are involved in disulfide bond formation, instead of disulfide reduction, which is related to the oxidative environment where they are found. PDI enzymes and DsbC are endowed with disulfide isomerase activity, which is related with their tetra-domain architecture. As illustrative description of specificity in thiol-disulfide exchange, redox aspects of transcription activation in bacteria, yeast, and mammals are presented in an evolutionary perspective. Therefore, thiol-disulfide exchange reactions play important roles in conferring specificity to pathways, a required feature for signaling.

Single-Cell Analysis Reveals that Insulation Maintains Signaling Specificity between Two Yeast MAPK Pathways with Common Components

PubMed Central

Patterson, Jesse C.; Klimenko, Evguenia S.; Thorner, Jeremy

2014-01-01

Eukaryotic cells use multiple mitogen-activated protein kinase (MAPK) cascades to evoke appropriate responses to external stimuli. In Saccharomyces cerevisiae, the MAPK Fus3 is activated by pheromone-binding G protein-coupled receptors to promote mating, whereas the MAPK Hog1 is activated by hyperosmotic stress to elicit the high osmolarity glycerol (HOG) response. Although these MAPK pathways share several upstream components, exposure to either pheromone or osmolyte alone triggers only the appropriate response. We used fluorescent localization- and transcription-specific reporters to assess activation of these pathways in individual cells on the minute and hour timescale, respectively. Dual activation of these two MAPK pathways occurred over a broad range of stimulant concentrations and temporal regimes in wild-type cells subjected to co-stimulation. Thus, signaling specificity is achieved through an “insulation” mechanism, not a “cross-inhibition” mechanism. Furthermore, we showed that there was a critical period during which Hog1 activity had to occur for proper insulation of the HOG pathway. PMID:20959523

Induced Radioactivity in Recovered Skylab Materials. [gamma ray spectra

NASA Technical Reports Server (NTRS)

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

1980-01-01

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

ESTIMATION OF CHEMICAL SPECIFIC PARAMETERS WITHIN PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC MODELS

EPA Science Inventory

While relationships between chemical structure and observed properties or activities (QSAR - quantitative structure activity relationship) can be used to predict the behavior of unknown chemicals, this method is semiempirical in nature relying on high quality experimental data to...

Angiotensin-converting enzyme inhibitory activity in Mexican Fresco cheese.

PubMed

Torres-Llanez, M J; González-Córdova, A F; Hernandez-Mendoza, A; Garcia, H S; Vallejo-Cordoba, B

2011-08-01

The objective of this study was to evaluate if Mexican Fresco cheese manufactured with specific lactic acid bacteria (LAB) presented angiotensin I-converting enzyme inhibitory (ACEI) activity. Water-soluble extracts (3 kDa) obtained from Mexican Fresco cheese prepared with specific LAB (Lactococcus, Lactobacillus, Enterococcus, and mixtures: Lactococcus-Lactobacillus and Lactococcus-Enterococcus) were evaluated for ACEI activity. Specific peptide fractions with high ACEI were analyzed using reverse phase-HPLC coupled to mass spectrometry for determination of amino acid sequence. Cheese containing Enterococcus faecium or a Lactococcus lactis ssp. lactis-Enterococcus faecium mixture showed the largest number of fractions with ACEI activity and the lowest half-maximal inhibitory concentration (IC(50); <10 μg/mL). Various ACEI peptides derived from β-casein [(f(193-205), f(193-207), and f(193-209)] and α(S1)-casein [f(1-15), f(1-22), f(14-23), and f(24-34)] were found. The Mexican Fresco cheese manufactured with specific LAB strains produced peptides with potential antihypertensive activity. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

DEVELOPMENT OF SULFHYDRYL-REACTIVE SILICA FOR PROTEIN IMMOBILIZATION IN HIGH-PERFORMANCE AFFINITY CHROMATOGRAPHY

PubMed Central

Mallik, Rangan; Wa, Chunling; Hage, David S.

2008-01-01

Two techniques were developed for the immobilization of proteins and other ligands to silica through sulfhydryl groups. These methods made use of maleimide-activated silica (the SMCC method) or iodoacetyl-activated silica (the SIA method). The resulting supports were tested for use in high-performance affinity chromatography by employing human serum albumin (HSA) as a model protein. Studies with normal and iodoacetamide-modified HSA indicated that these methods had a high selectivity for sulfhydryl groups on this protein, which accounted for the coupling of 77–81% of this protein to maleimide- or iodacetyl-activated silica. These supports were also evaluated in terms of their total protein content, binding capacity, specific activity, non-specific binding, stability and chiral selectivity for several test solutes. HSA columns prepared using maleimide-activated silica gave the best overall results for these properties when compared to HSA that had been immobilized to silica through the Schiff base method (i.e., an amine-based coupling technique). A key advantage of the supports developed in this work is that they offer the potential of giving greater site-selective immobilization and ligand activity than amine-based coupling methods. These features make these supports attractive in the development of protein columns for such applications as the study of biological interactions and chiral separations. PMID:17297940

High-Mannose Specific Lectin and Its Recombinants from a Carrageenophyta Kappaphycus alvarezii Represent a Potent Anti-HIV Activity Through High-Affinity Binding to the Viral Envelope Glycoprotein gp120.

PubMed

Hirayama, Makoto; Shibata, Hiromi; Imamura, Koji; Sakaguchi, Takemasa; Hori, Kanji

2016-02-01

We previously reported that a high-mannose binding lectin KAA-2 from the red alga Kappaphycus alvarezii, which is an economically important species and widely cultivated as a source of carrageenans, had a potent anti-influenza virus activity. In this study, the full-length sequences of two KAA isoforms, KAA-1 and KAA-2, were elucidated by a combination of peptide mapping and complementary DNA (cDNA) cloning. They consisted of four internal tandem-repeated domains, which are conserved in high-mannose specific lectins from lower organisms, including a cyanobacterium Oscillatoria agardhii and a red alga Eucheuma serra. Using an Escherichia coli expression system, an active recombinant form of KAA-1 (His-tagged rKAA-1) was successfully generated in the yield of 115 mg per liter of culture. In a detailed oligosaccharide binding analysis by a centrifugal ultrafiltration-HPLC method with 27 pyridylaminated oligosaccharides, His-tagged rKAA-1 and rKAA-1 specifically bound to high-mannose N-glycans with an exposed α1-3 mannose in the D2 arm as the native lectin did. Predicted from oligosaccharide binding specificity, a surface plasmon resonance analysis revealed that the recombinants exhibit strong interaction with gp120, a heavily glycosylated envelope glycoprotein of HIV with high association constants (1.48 - 1.61 × 10(9) M(-1)). Native KAAs and the recombinants inhibited the HIV-1 entry at IC50s of low nanomolar levels (7.3-12.9 nM). Thus, the recombinant proteins would be useful as antiviral reagents targeting the viral surface glycoproteins with high-mannose N-glycans, and the cultivated alga K. alvarezii could also be a good source of not only carrageenans but also this functional lectin(s).

High-Mannose Specific Lectin and Its Recombinants from a Carrageenophyta Kappaphycus alvarezii Represent a Potent Anti-HIV Activity Through High-Affinity Binding to the Viral Envelope Glycoprotein gp120.

PubMed

Hirayama, Makoto; Shibata, Hiromi; Imamura, Koji; Sakaguchi, Takemasa; Hori, Kanji

2016-04-01

We previously reported that a high-mannose binding lectin KAA-2 from the red alga Kappaphycus alvarezii, which is an economically important species and widely cultivated as a source of carrageenans, had a potent anti-influenza virus activity. In this study, the full-length sequences of two KAA isoforms, KAA-1 and KAA-2, were elucidated by a combination of peptide mapping and cDNA cloning. They consisted of four internal tandem-repeated domains, which are conserved in high-mannose specific lectins from lower organisms, including a cyanobacterium Oscillatoria agardhii and a red alga Eucheuma serra. Using an Escherichia coli expression system, an active recombinant form of KAA-1 (His-tagged rKAA-1) was successfully generated in the yield of 115 mg per a litter of culture. In a detailed oligosaccharide binding analysis by a centrifugal ultrafiltration-HPLC method with 27 pyridylaminated oligosaccharides, His-tagged rKAA-1 and rKAA-1 specifically bound to high-mannose N-glycans with an exposed α1-3 mannose in the D2 arm as the native lectin did. Predicted from oligosaccharide-binding specificity, a surface plasmon resonance analysis revealed that the recombinants exhibit strong interaction with gp120, a heavily glycosylated envelope glycoprotein of HIV with high association constants (1.48-1.61 × 10(9) M(-1)). Native KAAs and the recombinants inhibited the HIV-1 entry at IC50s of low nanomolar levels (7.3-12.9 nM). Thus, the recombinant proteins would be useful as antiviral reagents targeting the viral surface glycoproteins with high-mannose N-glycans, and the cultivated alga K. alvarezii could also be a good source of not only carrageenans but also this functional lectin(s).

The validity of activity monitors for measuring sleep in elite athletes.

PubMed

Sargent, Charli; Lastella, Michele; Halson, Shona L; Roach, Gregory D

2016-10-01

There is a growing interest in monitoring the sleep of elite athletes. Polysomnography is considered the gold standard for measuring sleep, however this technique is impractical if the aim is to collect data simultaneously with multiple athletes over consecutive nights. Activity monitors may be a suitable alternative for monitoring sleep, but these devices have not been validated against polysomnography in a population of elite athletes. Participants (n=16) were endurance-trained cyclists participating in a 6-week training camp. A total of 122 nights of sleep were recorded with polysomnography and activity monitors simultaneously. Agreement, sensitivity, and specificity were calculated from epoch-for-epoch comparisons of polysomnography and activity monitor data. Sleep variables derived from polysomnography and activity monitors were compared using paired t-tests. Activity monitor data were analysed using low, medium, and high sleep-wake thresholds. Epoch-for-epoch comparisons showed good agreement between activity monitors and polysomnography for each sleep-wake threshold (81-90%). Activity monitors were sensitive to sleep (81-92%), but specificity differed depending on the threshold applied (67-82%). Activity monitors underestimated sleep duration (18-90min) and overestimated wake duration (4-77min) depending on the threshold applied. Applying the correct sleep-wake threshold is important when using activity monitors to measure the sleep of elite athletes. For example, the default sleep-wake threshold (>40 activity counts=wake) underestimates sleep duration by ∼50min and overestimates wake duration by ∼40min. In contrast, sleep-wake thresholds that have a high sensitivity to sleep (>80 activity counts=wake) yield the best combination of agreement, sensitivity, and specificity. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

High frequencies of circulating IFN-gamma-secreting CD8 cytotoxic T cells specific for a novel MHC class I-restricted Mycobacterium tuberculosis epitope in M. tuberculosis-infected subjects without disease.

PubMed

Pathan, A A; Wilkinson, K A; Wilkinson, R J; Latif, M; McShane, H; Pasvol, G; Hill, A V; Lalvani, A

2000-09-01

MHC class I-restricted CD8 cytotoxic T lymphocytes (CTL) are essential for protective immunity to Mycobacterium tuberculosis in animal models but their role in humans remains unclear. We therefore studied subjects who had successfully contained M. tuberculosis infection in vivo, i.e. exposed healthy household contacts and individuals with inactive self-healed pulmonary tuberculosis. Using the ELISPOT assay for IFN-gamma, we screened peptides from ESAT-6, a secreted antigen that is highly specific for M. tuberculosis. We identified a novel nonamer epitope: unstimulated peripheral blood-derived CD8 T cells displayed peptide-specific IFN-gamma release ex vivo while CD8 T cell lines and clones exhibited HLA-A68.02-restricted cytolytic activity and recognized endogenously processed antigen. The frequency of CD8 CTL specific for this single M. tuberculosis epitope, 1/2500 peripheral blood lymphocytes, was equivalent to the combined frequency of all IFN-gamma-secreting purified protein derivative-reactive T cells ex vivo. This highly focused CTL response was maintained in an asymptomatic contact over 2 years and is the most potent antigen-specific antimycobacterial CD8 CTL response hitherto described. Thus, human M. tuberculosis-specific CD8 CTL are not necessarily associated with active disease per se. Rather, our results are consistent with a protective role for these ESAT-6-specific CD8 T cells in the long-term control of M. tuberculosis in vivo in humans.

Build a Bird House. Grades 3-5.

ERIC Educational Resources Information Center

Rushton, Erik; Ryan, Emily; Swift, Charles

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

Nanostructured TiO2 surfaces promote polarized activation of microglia, but not astrocytes, toward a proinflammatory profile

NASA Astrophysics Data System (ADS)

de Astis, Silvia; Corradini, Irene; Morini, Raffaella; Rodighiero, Simona; Tomasoni, Romana; Lenardi, Cristina; Verderio, Claudia; Milani, Paolo; Matteoli, Michela

2013-10-01

Activation of glial cells, including astrocytes and microglia, has been implicated in the inflammatory responses underlying brain injury and neurodegenerative diseases including Alzheimer's and Parkinson's diseases. The classic activation state (M1) is characterized by high capacity to present antigens, high production of nitric oxide (NO) and reactive oxygen species (ROS) and proinflammatory cytokines. Classically activated cells act as potent effectors that drive the inflammatory response and may mediate detrimental effects on neural cells. The second phenotype (M2) is an alternative, apparently beneficial, activation state, more related to a fine tuning of inflammation, scavenging of debris, promotion of angiogenesis, tissue remodeling and repair. Specific environmental chemical signals are able to induce these different polarization states. We provide here evidence that nanostructured substrates are able, exclusively in virtue of their physical properties, to push microglia toward the proinflammatory activation phenotype, with an efficacy which reflects the graded nanoscale rugosity. The acquisition of a proinflammatory phenotype appears specific for microglia and not astrocytes, indicating that these two cell types, although sharing common innate immune responses, respond differently to external physical stimuli.

Essential Oil Variability and Biological Activities of Tetraclinis articulata (Vahl) Mast. Wood According to the Extraction Time.

PubMed

Djouahri, Abderrahmane; Saka, Boualem; Boudarene, Lynda; Baaliouamer, Aoumeur

2016-12-01

In the present work, the hydrodistillation (HD) and microwave-assisted hydrodistillation (MAHD) kinetics of essential oil (EO) extracted from Tetraclinis articulata (Vahl) Mast. wood was conducted, in order to assess the impact of extraction time and technique on chemical composition and biological activities. Gas chromatography (GC) and GC/mass spectrometry analyses showed significant differences between the extracted EOs, where each family class or component presents a specific kinetic according to extraction time, technique and especially for the major components: camphene, linalool, cedrol, carvacrol and α-acorenol. Furthermore, our findings showed a high variability for both antioxidant and anti-inflammatory activities, where each activity has a specific effect according to extraction time and technique. The highlighted variability reflects the high impact of extraction time and technique on chemical composition and biological activities, which led to conclude that we should select EOs to be investigated carefully depending on extraction time and technique, in order to isolate the bioactive components or to have the best quality of EO in terms of biological activities and preventive effects in food. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

Discovery of a potent and highly specific β2 proteasome inhibitor from a library of copper complexes.

PubMed

Zhou, Tongliang; Cai, Yuanbo; Liang, Lei; Yang, Lingfei; Xu, Fengrong; Niu, Yan; Wang, Chao; Zhang, Jun-Long; Xu, Ping

2016-12-01

We reported the synthesis, characterization and biological activity of several copper(II) Schiff base complexes, which exhibit high proteasome inhibitory activities with particular selectivity of β 2 subunit. Structure-activity relationships information obtained from complex Na 2 [Cu(a4s1)] demonstrated that distinct bonding modes in β 2 and β 5 subunits determines its selectivity and potent inhibition for β 2 subunit. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

PubMed

Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

2016-03-04

Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

Tumor-specific novel taxoid-monoclonal antibody conjugates.

PubMed

Ojima, Iwao; Geng, Xudong; Wu, Xinyuan; Qu, Chuanxing; Borella, Christopher P; Xie, Hongsheng; Wilhelm, Sharon D; Leece, Barbara A; Bartle, Laura M; Goldmacher, Victor S; Chari, Ravi V J

2002-12-19

Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice.

Agonistic aptamer to the insulin receptor leads to biased signaling and functional selectivity through allosteric modulation

PubMed Central

Yunn, Na-Oh; Koh, Ara; Han, Seungmin; Lim, Jong Hun; Park, Sehoon; Lee, Jiyoun; Kim, Eui; Jang, Sung Key; Berggren, Per-Olof; Ryu, Sung Ho

2015-01-01

Due to their high affinity and specificity, aptamers have been widely used as effective inhibitors in clinical applications. However, the ability to activate protein function through aptamer-protein interaction has not been well-elucidated. To investigate their potential as target-specific agonists, we used SELEX to generate aptamers to the insulin receptor (IR) and identified an agonistic aptamer named IR-A48 that specifically binds to IR, but not to IGF-1 receptor. Despite its capacity to stimulate IR autophosphorylation, similar to insulin, we found that IR-A48 not only binds to an allosteric site distinct from the insulin binding site, but also preferentially induces Y1150 phosphorylation in the IR kinase domain. Moreover, Y1150-biased phosphorylation induced by IR-A48 selectively activates specific signaling pathways downstream of IR. In contrast to insulin-mediated activation of IR, IR-A48 binding has little effect on the MAPK pathway and proliferation of cancer cells. Instead, AKT S473 phosphorylation is highly stimulated by IR-A48, resulting in increased glucose uptake both in vitro and in vivo. Here, we present IR-A48 as a biased agonist able to selectively induce the metabolic activity of IR through allosteric binding. Furthermore, our study also suggests that aptamers can be a promising tool for developing artificial biased agonists to targeted receptors. PMID:26245346

Rare-gas effects on metabolism and inert gas narcosis

NASA Technical Reports Server (NTRS)

1972-01-01

The detailed examination is reported of the theory that narcosis results from expansion of the cell membrane under high partial pressures. The research is partially based on the hypothesis that, like oxygen toxicity, the mechanism of metabolic effects of rare gases may be similar at both low and high pressures and are simply more observable at high pressures. Using adult female goats, the parameters measured include oxygen consumption, CO2 production, respiration rate, heart rate, rectal and skin temperatures and the analysis of electroencephalograms and evoked response. Additionally, the specific activity is measured of plasma glucose subsequent to injection of glucose-UL-C-14, intravenous infusion, specific activity of expired CO2, unesterified fatty acid levels and whole blood lactate-to-pyruvate ratios. Also studied were the effects of acetylsalicylic acid, vitamin E and cationic detergents (which alleviate narcosis) upon metabolic changes induced by high pressure narcosis.

Nitrogen and phosphorus co-doped carbon hollow spheres derived from polypyrrole for high-performance supercapacitor electrodes

NASA Astrophysics Data System (ADS)

Lv, Bingjie; Li, Peipei; Liu, Yan; Lin, Shanshan; Gao, Bifen; Lin, Bizhou

2018-04-01

Nitrogen and phosphorus co-doped carbon hollow spheres (NPCHSs) have been prepared by a carbonization and subsequent chemical activation route using dehydrated polypyrrole hollow spheres as the precursor and KOH as the activating agent. NPCHSs are interconnected into a unique 3D porous network, which endows the as-prepared carbon to exhibit a large specific surface area of 1155 m2 g-1 and a high specific capacitance of 232 F g-1 at a current density of 1 A g-1. The as-obtained NPCHSs present a high-level heteroatom doping with N, O and P contents of 11.4, 6.7 and 3.5 wt%, respectively. The capacitance of NPCHSs has been retained at 89.1% after 5000 charge-discharge cycles at a relatively high current density of 5 A g-1. Such excellent performance suggests that NPCHSs are attractive electrode candidates for electrical double layer capacitors.

Activity and Phylogenetic Diversity of Bacterial Cells with High and Low Nucleic Acid Content and Electron Transport System Activity in an Upwelling Ecosystem

PubMed Central

Longnecker, K.; Sherr, B. F.; Sherr, E. B.

2005-01-01

We evaluated whether bacteria with higher cell-specific nucleic acid content (HNA) or an active electron transport system, i.e., positive for reduction of 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), were responsible for the bulk of bacterioplankton metabolic activity. We also examined whether the phylogenetic diversity of HNA and CTC-positive cells differed from the diversity of Bacteria with low nucleic acid content (LNA). Bacterial assemblages were sampled both in eutrophic shelf waters and in mesotrophic offshore waters in the Oregon coastal upwelling region. Cytometrically sorted HNA, LNA, and CTC-positive cells were assayed for their cell-specific [3H]leucine incorporation rates. Phylogenetic diversity in sorted non-radioactively labeled samples was assayed using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes. Cell-specific rates of leucine incorporation of HNA and CTC-positive cells were on average only slightly greater than the cell-specific rates of LNA cells. HNA cells accounted for most bacterioplankton substrate incorporation due to high abundances, while the low abundances of CTC-positive cells resulted in only a small contribution by these cells to total bacterial activity. The proportion of the total bacterial leucine incorporation attributable to LNA cells was higher in offshore regions than in shelf waters. Sequence data obtained from DGGE bands showed broadly similar phylogenetic diversity across HNA, LNA, and CTC-positive cells, with between-sample and between-region variability in the distribution of phylotypes. Our results suggest that LNA bacteria are not substantially different from HNA bacteria in either cell-specific rates of substrate incorporation or phylogenetic composition and that they can be significant contributors to bacterial metabolism in the sea. PMID:16332746

Activity and phylogenetic diversity of bacterial cells with high and low nucleic acid content and electron transport system activity in an upwelling ecosystem.

PubMed

Longnecker, K; Sherr, B F; Sherr, E B

2005-12-01

We evaluated whether bacteria with higher cell-specific nucleic acid content (HNA) or an active electron transport system, i.e., positive for reduction of 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), were responsible for the bulk of bacterioplankton metabolic activity. We also examined whether the phylogenetic diversity of HNA and CTC-positive cells differed from the diversity of Bacteria with low nucleic acid content (LNA). Bacterial assemblages were sampled both in eutrophic shelf waters and in mesotrophic offshore waters in the Oregon coastal upwelling region. Cytometrically sorted HNA, LNA, and CTC-positive cells were assayed for their cell-specific [3H]leucine incorporation rates. Phylogenetic diversity in sorted non-radioactively labeled samples was assayed using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes. Cell-specific rates of leucine incorporation of HNA and CTC-positive cells were on average only slightly greater than the cell-specific rates of LNA cells. HNA cells accounted for most bacterioplankton substrate incorporation due to high abundances, while the low abundances of CTC-positive cells resulted in only a small contribution by these cells to total bacterial activity. The proportion of the total bacterial leucine incorporation attributable to LNA cells was higher in offshore regions than in shelf waters. Sequence data obtained from DGGE bands showed broadly similar phylogenetic diversity across HNA, LNA, and CTC-positive cells, with between-sample and between-region variability in the distribution of phylotypes. Our results suggest that LNA bacteria are not substantially different from HNA bacteria in either cell-specific rates of substrate incorporation or phylogenetic composition and that they can be significant contributors to bacterial metabolism in the sea.

Microbiota diversity and gene expression dynamics in human oral biofilms

PubMed Central

2014-01-01

Background Micro-organisms inhabiting teeth surfaces grow on biofilms where a specific and complex succession of bacteria has been described by co-aggregation tests and DNA-based studies. Although the composition of oral biofilms is well established, the active portion of the bacterial community and the patterns of gene expression in vivo have not been studied. Results Using RNA-sequencing technologies, we present the first metatranscriptomic study of human dental plaque, performed by two different approaches: (1) A short-reads, high-coverage approach by Illumina sequencing to characterize the gene activity repertoire of the microbial community during biofilm development; (2) A long-reads, lower-coverage approach by pyrosequencing to determine the taxonomic identity of the active microbiome before and after a meal ingestion. The high-coverage approach allowed us to analyze over 398 million reads, revealing that microbial communities are individual-specific and no bacterial species was detected as key player at any time during biofilm formation. We could identify some gene expression patterns characteristic for early and mature oral biofilms. The transcriptomic profile of several adhesion genes was confirmed through qPCR by measuring expression of fimbriae-associated genes. In addition to the specific set of gene functions overexpressed in early and mature oral biofilms, as detected through the short-reads dataset, the long-reads approach detected specific changes when comparing the metatranscriptome of the same individual before and after a meal, which can narrow down the list of organisms responsible for acid production and therefore potentially involved in dental caries. Conclusions The bacteria changing activity during biofilm formation and after meal ingestion were person-specific. Interestingly, some individuals showed extreme homeostasis with virtually no changes in the active bacterial population after food ingestion, suggesting the presence of a microbial community which could be associated to dental health. PMID:24767457

Microbiota diversity and gene expression dynamics in human oral biofilms.

PubMed

Benítez-Páez, Alfonso; Belda-Ferre, Pedro; Simón-Soro, Aurea; Mira, Alex

2014-04-27

Micro-organisms inhabiting teeth surfaces grow on biofilms where a specific and complex succession of bacteria has been described by co-aggregation tests and DNA-based studies. Although the composition of oral biofilms is well established, the active portion of the bacterial community and the patterns of gene expression in vivo have not been studied. Using RNA-sequencing technologies, we present the first metatranscriptomic study of human dental plaque, performed by two different approaches: (1) A short-reads, high-coverage approach by Illumina sequencing to characterize the gene activity repertoire of the microbial community during biofilm development; (2) A long-reads, lower-coverage approach by pyrosequencing to determine the taxonomic identity of the active microbiome before and after a meal ingestion. The high-coverage approach allowed us to analyze over 398 million reads, revealing that microbial communities are individual-specific and no bacterial species was detected as key player at any time during biofilm formation. We could identify some gene expression patterns characteristic for early and mature oral biofilms. The transcriptomic profile of several adhesion genes was confirmed through qPCR by measuring expression of fimbriae-associated genes. In addition to the specific set of gene functions overexpressed in early and mature oral biofilms, as detected through the short-reads dataset, the long-reads approach detected specific changes when comparing the metatranscriptome of the same individual before and after a meal, which can narrow down the list of organisms responsible for acid production and therefore potentially involved in dental caries. The bacteria changing activity during biofilm formation and after meal ingestion were person-specific. Interestingly, some individuals showed extreme homeostasis with virtually no changes in the active bacterial population after food ingestion, suggesting the presence of a microbial community which could be associated to dental health.

[Tissue-specific nucleoprotein complexes].

PubMed

Riadnova, I Iu; Shataeva, L K; Khavinson, V Kh

2000-01-01

A method of isolation of native nucleorprotein complexes from cattle cerebral cortex, thymus, and liver was developed. Compositions of these complexes were studied by means of gel-chromatography and ion-exchange chromatography. These preparations were shown to consist of several fractions of proteins and their complexes differ by molecular mass and electro-chemical properties. Native nucleoprotein complexes revealed high tissue specific activity, which was not species-specific.

Electrolytes with Improved Safety Characteristics for High Voltage, High Specific Energy Li-ion Cells

NASA Technical Reports Server (NTRS)

Smart, M. C.; Krause, F. C.; Hwang, C.; West, W. C.; Soler, J.; Whitcanack, L. W.; Prakash, G. K. S.; Ratnakumar, B. V.

2012-01-01

(1) NASA is actively pursuing the development of advanced electrochemical energy storage and conversion devices for future lunar and Mars missions; (2) The Exploration Technology Development Program, Energy Storage Project is sponsoring the development of advanced Li-ion batteries and PEM fuel cell and regenerative fuel cell systems for the Altair Lunar Lander, Extravehicular Activities (EVA), and rovers and as the primary energy storage system for Lunar Surface Systems; (3) At JPL, in collaboration with NASA-GRC, NASA-JSC and industry, we are actively developing advanced Li-ion batteries with improved specific energy, energy density and safety. One effort is focused upon developing Li-ion battery electrolyte with enhanced safety characteristics (i.e., low flammability); and (4) A number of commercial applications also require Li-ion batteries with enhanced safety, especially for automotive applications.

3D architecture of a graphene/CoMoO(4) composite for asymmetric supercapacitors usable at various temperatures.

PubMed

Jiang, Yaru; Zheng, Xin; Yan, Xiaoqin; Li, Yong; Zhao, Xuan; Zhang, Yue

2017-05-01

Designing and optimizing the electrode materials and studying the electrochemical performance or cycle life of the supercapacitor under different working conditions are crucial to its practical application. Herein, we proposed a rational design of 3D-graphene/CoMoO 4 nanoplates by a facile two-step hydrothermal method. Owing to the high electron transfer rate of graphene and the high activity of the CoMoO 4 nanoplates, the three-dimensional electrode architectures achieved remarkable electrochemical performances with high areal specific capacitance (1255.24F/g at 1A/g) and superior cycling stability (91.3% of the original specific capacitance after 3000 cycles at 1A/g). The all-solid-state asymmetric supercapacitor composed of 3D-graphene/CoMoO 4 and activated carbon (AC) exhibited a specific capacitance of 109F/g at 0.2A/g and an excellent cycling stability with only 12.1% of the initial specific capacitance off after 3000 cycles at 2A/g. The effects of temperature and charge-discharge current densities on the charge storage capacity of the supercapacitor were also investigated in detail for practical applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S -Transferases

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

Stoddard, Ethan G.; Killinger, Bryan J.; Nair, Reji N.

Glutathione S-transferases (GSTs) comprise a highly diverse family of phase II drug metabolizing enzymes whose shared function is the conjugation of reduced glutathione to various endo- and xenobiotics. Although the conglomerate activity of these enzymes can be measured by colorimetric assays, measurement of the individual contribution from specific isoforms and their contribution to the detoxification of xenobiotics in complex biological samples has not been possible. For this reason, we have developed two activity-based probes that characterize active glutathione transferases in mammalian tissues. The GST active site is comprised of a glutathione binding “G site” and a distinct substrate binding “Hmore » site”. Therefore, we developed (1) a glutathione-based photoaffinity probe (GSH-ABP) to target the “G site”, and (2) a probe designed to mimic a substrate molecule and show “H site” activity (GST-ABP). The GSH-ABP features a photoreactive moiety for UV-induced covalent binding to GSTs and glutathione-binding enzymes. The GST-ABP is a derivative of a known mechanism-based GST inhibitor that binds within the active site and inhibits GST activity. Validation of probe targets and “G” and “H” site specificity was carried out using a series of competitors in liver homogenates. Herein, we present robust tools for the novel characterization of enzyme- and active site-specific GST activity in mammalian model systems.« less

LH-RH binding to purified pituitary plasma membranes: absence of adenylate cyclase activation.

PubMed

Clayton, R N; Shakespear, R A; Marshall, J C

1978-06-01

Purified bovine pituitary plasma membranes possess two specific LH-RH binding sites. The high affinity site (2.5 X 10(9) l/mol) has low capacity (9 X 10(-15) mol/mg membrane protein) while the low affinity site 6.1 X 10(5) l/mol) has a much higher capacity (1.1 X 10(-10) mol/mg). Specific LH-RH binding to plasma membranes is increased 8.5-fold during purification from homogenate whilst adenylate cyclase activity is enriched 7--8-fold. Distribution of specific LH-RH binding to sucrose density gradient interface fractions parallels that of adenylate cyclase activity. Mg2+ and Ca2+ inhibit specific [125I]LH-RH binding at micromolar concentrations. Synthetic LH-RH, up to 250 microgram/ml, failed to stimulate adenylase cyclase activity of the purified bovine membranes. Using a crude 10,800 g rat pituitary membrane preparation, LH-RH similarly failed to activate adenylate cyclase even in the presence of guanyl nucleotides. These data confirm the presence of LH-RH receptor sites on pituitary plasma membranes and suggest that LH-RH-induced gonadotrophin release may be mediated by mechanisms other than activation of adenylate cyclase.

Hierarchical porous carbon materials derived from petroleum pitch for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Abudu, Patiman; Wang, Luxiang; Xu, Mengjiao; Jia, Dianzeng; Wang, Xingchao; Jia, Lixia

2018-06-01

In this work, a honeycomb-like carbon material derived from petroleum pitch was synthesized by a simple one-step carbonization/activation method using silica nanospheres as the hard templates. The obtained hierarchical porous carbon materials (HPCs) with a large specific surface area and uniform macropore distribution provide abundant active sites and sufficient ion migration channels. When used as an electrode material for supercapacitors, the HPCs exhibit a high specific capacitance of 341.0 F g-1 at 1 A g-1, excellent rate capability with a capacitance retention of 55.6% at 50 A g-1 (189.5 F g-1), and outstanding cycling performance in the three-electrode system.

High Specific Activity Tritium-Labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): A High Affinity 5-HT2A Receptor-Selective Agonist Radioligand

PubMed Central

Nichols, David E.; Frescas, Stewart P.; Chemel, Benjamin R.; Rehder, Kenneth S.; Zhong, Desong; Lewin, Anita H.

2009-01-01

The title compound ([3H]INBMeO) was prepared by an O,O-dimethylation reaction of a t-BOC protected diphenolic precursor using no carrier added tritiated iodomethane in DMF with K2CO3. Removal of the t-BOC protecting group and purification by HPLC afforded an overall yield of 43%, with a radiochemical purity of 99% and specific activity of 164 Ci/mmol. The new radioligand was suitable for labeling human 5-HT2A receptors in two heterologous cell lines and had about 20-fold higher affinity than [3H]ketanserin. PMID:18468904

Extensive peptide and natural protein substrate screens reveal that mouse caspase-11 has much narrower substrate specificity than caspase-1

PubMed Central

Ramirez, Monica L. Gonzalez; Poreba, Marcin; Snipas, Scott J.; Groborz, Katarzyna; Drag, Marcin; Salvesen, Guy S.

2018-01-01

Inflammatory cell death, or pyroptosis, is triggered by pathogenic infections or events. It is executed by caspase-1 (in the canonical pyroptosis pathway) or caspase-11 (noncanonical pathway), each via production of a cell-lytic domain from the pyroptosis effector protein gasdermin D through specific and limited proteolysis. Pyroptosis is accompanied by the release of inflammatory mediators, including the proteolytically processed forms of interleukin-1β (IL-1β) and IL-18. Given the similar inflammatory outcomes of the canonical and noncanonical pyroptosis pathways, we hypothesized that caspase-1 and -11 should have very similar activities and substrate specificities. To test this hypothesis, we purified recombinant murine caspases and analyzed their primary specificities by massive hybrid combinatorial substrate library (HyCoSuL) screens. We correlated the substrate preferences of each caspase with their activities on the recombinant natural substrates IL-1β, IL-18, and gasdermin D. Although we identified highly selective and robust peptidyl substrates for caspase-1, we were unable to do so for caspase-11, because caspase-1 cleaved even the best caspase-11 substrates equally well. Caspase-1 rapidly processed pro-IL-1β and -18, but caspase-11 processed these two pro-ILs extremely poorly. However, both caspase-1 and -11 efficiently produced the cell-lytic domain from the gasdermin D precursor. We hypothesize that caspase-11 may have evolved a specific exosite to selectively engage pyroptosis without directly activating pro-IL-1β or -18. In summary, comparing the activities of caspase-1 and -11 in HyCoSuL screens and with three endogenous protein substrates, we conclude that caspase-11 has highly restricted substrate specificity, preferring gasdermin D over all other substrates examined. PMID:29414788

Investigations of the structure and function of bacterial communities associated with Sphagnum mosses.

PubMed

Opelt, Katja; Chobot, Vladimir; Hadacek, Franz; Schönmann, Susan; Eberl, Leo; Berg, Gabriele

2007-11-01

High acidity, low temperature and extremely low concentration of nutrients form Sphagnum bogs into extreme habitats for organisms. Little is known about the bacteria associated with living Sphagnum plantlets, especially about their function for the host. Therefore, we analysed the endo- and ectophytic bacterial populations associated with two widely distributed Sphagnum species, Sphagnum magellanicum and Sphagnum fallax, by a multiphasic approach. The screening of 1222 isolates for antagonistic activity resulted in 326 active isolates. The bacterial communities harboured a high proportion of antifungal (26%) but a low proportion of antibacterial isolates (0.4%). Members of the genus Burkholderia (38%) were found to be the most dominant group of antagonistic bacteria. The finding that a large proportion (89%) of the antagonistic bacteria produced antifungal compounds may provide an explanation for the well-known antimicrobial activity of certain Sphagnum species. The secondary metabolites of the Sphagnum species themselves were analysed by HPLC-PDA. The different spectra of detected compounds may not only explain the antifungal activity but also the species specificity of the microbial communities. The latter was analysed using cultivation-independent single-stranded conformation polymorphism (SSCP) analysis. Using Burkholderia-specific primers we found a high diversity of Burkholderia isolates in the endophytic and ectophytic habitats of Sphagnum. Furthermore, a high diversity of nitrogen-fixing bacteria was detected by using nifH-specific primers, especially inside Sphagnum mosses. In conclusion, this study provides evidence that both Sphagnum species were colonized by characteristic bacterial populations, which appear to be important for pathogen defence and nitrogen fixation.

Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators

PubMed Central

Polstein, Lauren R.; Perez-Pinera, Pablo; Kocak, D. Dewran; Vockley, Christopher M.; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E.; Reddy, Timothy E.; Gersbach, Charles A.

2015-01-01

Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. PMID:26025803

[Science in the Outdoors].

ERIC Educational Resources Information Center

Sarage, Joe; And Others

Designed for instruction of emotionally handicapped children and youth, this resource guide presents science activities and concepts relative to rural and urban outdoor education. Included are 25 different articles, varying from broadly generalized to highly specific concept/activity suggestions which include film and book bibliographies and…

Synthesis of Highly Active Sub-Nanometer Pt@Rh Core-Shell Nanocatalyst via a Photochemical Route: Porous Titania Nanoplates as a Superior Photoactive Support.

PubMed

Zhan, Wen-Wen; Zhu, Qi-Long; Dang, Song; Liu, Zheng; Kitta, Mitsunori; Suenaga, Kazutomo; Zheng, Lan-Sun; Xu, Qiang

2017-04-01

Sub-nanometer Pt@Rh nanoparticles highly dispersed on MIL-125-derived porous TiO 2 nanoplates are successfully prepared for the first time by a photochemical route, where the porous TiO 2 nanoplates with a relatively high specific surface area play a dual role as both effective photoreductant and catalyst support. The resulting Pt@Rh/p-TiO 2 can be utilized as a highly active catalyst. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alcohol Dehydrogenase Activities of Wine Yeasts in Relation to Higher Alcohol Formation

PubMed Central

Singh, Rajendra; Kunkee, Ralph E.

1976-01-01

Alcohol dehydrogenase activities were examined in cell-free extracts of 10 representative wine yeast strains having various productivities of higher alcohols (fusel oil). The amount of fusel alcohols (n-propanol, isobutanol, active pentanol, and isopentanol) produced by the different yeasts and the specific alcohol dehydrogenase activities with the corresponding alcohols as substrates were found to be significantly related. No such relationship was found for ethanol. The amounts of higher alcohols formed during vinification could be predicted from the specific activities of the alcohol dehydrogenases with high accuracy. The results suggest a close relationship between the control of the activities of alcohol dehydrogenase and the formation of fusel oil alcohols. Also, new procedures for the prediction of higher alcohol formation during alcoholic beverage fermentation are suggested. PMID:16345179

A study on pore-opening behaviors of graphite nanofibers by a chemical activation process.

PubMed

Kim, Byung-Joo; Lee, Young-Seak; Park, Soo-Jin

2007-02-15

In this work, porous graphite nanofibers (GNFs) were prepared by a KOH activation method in order to manufacture porous carbon nanofibers. The process was conducted in the activation temperature range of 900-1100 degrees C, and the KOH:GNFs ratio was fixed at 3.5:1. The textural properties of the porous carbons were analyzed using N2 adsorption isotherms at 77 K. The BET, D-R, and BJH equations were used to observe the specific surface areas and the micro- and mesopore structures, respectively. From the results, it was found that the textural properties, including the specific surface area and the pore volumes, were proportionally enhanced with increasing activation temperatures. However, the activation mechanisms showed quite significant differences between the samples activated at low and high temperatures.

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

PubMed Central

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

1998-01-01

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

Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

PubMed

Luo, Wen-Hui; Yang, Ya-Wun

2016-04-01

The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

Synthesis of an excellent electrocatalyst for oxygen reduction reaction with supercritical fluid: Graphene cellular monolith with ultrafine and highly dispersive multimetallic nanoparticles

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

Zhou, Yazhou; Cheng, Xiaonong; Yen, Clive H.

Graphene cellular monolith (GCM) can be used as an excellent support for nanoparticles in widespread applications. However, it's still a great challenge to deposit the desirable nanoparticles in GCM that have small size, controllable structure, composition, and high dispersion using the current methods. Here we demonstrate a green, efficient and large-scale method to address this challenge using supercritical fluid (SCF). By this superior method, graphene hydrogel can be transferred into GCM while being deposited with ultrafine and highly dispersive nanoparticles. Specifically, the bimetallic PtFe/GCM and the trimetallic PtFeCo/GCM catalysts are successfully synthesized, and their electrocatalytic performances toward oxygen reduction reactionmore » (ORR) are also studied. The resultant PtFe/GCM shows the significant enhancement in ORR activity, including a factor of 8.47 enhancement in mass activity (0.72 A mgPt-1), and a factor of 7.67 enhancement in specific activity (0.92 mA cm-2), comparing with those of the commercial Pt/C catalyst (0.085 A mgPt-1, 0.12 mA cm-2). Importantly, by introducing the Co, the trimetallic PtFeCo/GCM exhibits the further improved ORR activities (1.28 A mgPt-1, 1.80 mA cm-2). The high ORR activity is probably attributed to the alloying structure, ultrafine size, highly dispersive, well-defined, and a better interface with 3D porous graphene support.« less

Synthesis of an excellent electrocatalyst for oxygen reduction reaction with supercritical fluid: Graphene cellular monolith with ultrafine and highly dispersive multimetallic nanoparticles

NASA Astrophysics Data System (ADS)

Zhou, Yazhou; Cheng, Xiaonong; Yen, Clive H.; Wai, Chien M.; Wang, Chongmin; Yang, Juan; Lin, Yuehe

2017-04-01

Graphene cellular monolith (GCM) can be used as an excellent support for nanoparticles in widespread applications. However, it's still a great challenge to deposit the desirable nanoparticles in GCM that have small size, controllable structure, composition, and high dispersion using the current methods. Here we demonstrate a green, efficient and large-scale method to address this challenge using supercritical fluid (SCF). By this superior method, graphene hydrogel can be transferred into GCM while being deposited with ultrafine and highly dispersive nanoparticles. Specifically, the bimetallic PtFe/GCM and the trimetallic PtFeCo/GCM catalysts are successfully synthesized, and their electrocatalytic performances toward oxygen reduction reaction (ORR) are also studied. The resultant PtFe/GCM shows the significant enhancement in ORR activity, including a factor of 8.47 enhancement in mass activity (0.72 A mgPt-1), and a factor of 7.67 enhancement in specific activity (0.92 mA cm-2), comparing with those of the commercial Pt/C catalyst (0.085 A mgPt-1, 0.12 mA cm-2). Importantly, by introducing the Co, the trimetallic PtFeCo/GCM exhibits the further improved ORR activities (1.28 A mgPt-1, 1.80 mA cm-2). The high ORR activity is probably attributed to the alloying structure, ultrafine size, highly dispersive, well-defined, and a better interface with 3D porous graphene support.

Highly Tissue Substructure-Specific Effects of Human Papilloma Virus in Mucosa of HIV-Infected Patients Revealed by Laser-Dissection Microscopy-Assisted Gene Expression Profiling

PubMed Central

Baumgarth, Nicole; Szubin, Richard; Dolganov, Greg M.; Watnik, Mitchell R.; Greenspan, Deborah; Da Costa, Maria; Palefsky, Joel M.; Jordan, Richard; Roederer, Mario; Greenspan, John S.

2004-01-01

Human papilloma virus (HPV) causes focal infections of epithelial layers in skin and mucosa. HIV-infected patients on highly active antiretroviral therapy (HAART) appear to be at increased risk of developing HPV-induced oral warts. To identify the mechanisms that allow long-term infection of oral epithelial cells in these patients, we used a combination of laser-dissection microscopy (LDM) and highly sensitive and quantitative, non-biased, two-step multiplex real-time RT-PCR to study pathogen-induced alterations of specific tissue subcompartments. Expression of 166 genes was compared in three distinct epithelial and subepithelial compartments isolated from biopsies of normal mucosa from HIV-infected and non-infected patients and of HPV32-induced oral warts from HIV-infected patients. In contrast to the underlying HIV infection and/or HAART, which did not significantly elaborate tissue substructure-specific effects, changes in oral warts were strongly tissue substructure-specific. HPV 32 seems to establish infection by selectively enhancing epithelial cell growth and differentiation in the stratum spinosum and to evade the immune system by actively suppressing inflammatory responses in adjacent underlying tissues. With this highly sensitive and quantitative method tissue-specific expression of hundreds of genes can be studied simultaneously in a few cells. Because of its large dynamic measurement range it could also become a method of choice to confirm and better quantify results obtained by microarray analysis. PMID:15331396

Nonribosomal biosynthesis of backbone-modified peptides

NASA Astrophysics Data System (ADS)

Niquille, David L.; Hansen, Douglas A.; Mori, Takahiro; Fercher, David; Kries, Hajo; Hilvert, Donald

2018-03-01

Biosynthetic modification of nonribosomal peptide backbones represents a potentially powerful strategy to modulate the structure and properties of an important class of therapeutics. Using a high-throughput assay for catalytic activity, we show here that an L-Phe-specific module of an archetypal nonribosomal peptide synthetase can be reprogrammed to accept and process the backbone-modified amino acid (S)-β-Phe with near-native specificity and efficiency. A co-crystal structure with a non-hydrolysable aminoacyl-AMP analogue reveals the origins of the 40,000-fold α/β-specificity switch, illuminating subtle but precise remodelling of the active site. When the engineered catalyst was paired with downstream module(s), (S)-β-Phe-containing peptides were produced at preparative scale in vitro (~1 mmol) and high titres in vivo (~100 mg l-1), highlighting the potential of biosynthetic pathway engineering for the construction of novel nonribosomal β-frameworks.

Process for forming a porous silicon member in a crystalline silicon member

DOEpatents

Northrup, M. Allen; Yu, Conrad M.; Raley, Norman F.

1999-01-01

Fabrication and use of porous silicon structures to increase surface area of heated reaction chambers, electrophoresis devices, and thermopneumatic sensor-actuators, chemical preconcentrates, and filtering or control flow devices. In particular, such high surface area or specific pore size porous silicon structures will be useful in significantly augmenting the adsorption, vaporization, desorption, condensation and flow of liquids and gasses in applications that use such processes on a miniature scale. Examples that will benefit from a high surface area, porous silicon structure include sample preconcentrators that are designed to adsorb and subsequently desorb specific chemical species from a sample background; chemical reaction chambers with enhanced surface reaction rates; and sensor-actuator chamber devices with increased pressure for thermopneumatic actuation of integrated membranes. Examples that benefit from specific pore sized porous silicon are chemical/biological filters and thermally-activated flow devices with active or adjacent surfaces such as electrodes or heaters.

Continuous directed evolution of aminoacyl-tRNA synthetases

PubMed Central

Bryson, David I.; Fan, Chenguang; Guo, Li-Tao; Miller, Corwin; Söll, Dieter; Liu, David R.

2017-01-01

Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site-specific installation of non-canonical amino acids (ncAAs) into proteins. Traditional evolution techniques typically produce AARSs with greatly reduced activity and selectivity compared to their wild-type counterparts. We designed phage-assisted continuous evolution (PACE) selections to rapidly produce highly active and selective orthogonal AARSs through hundreds of generations of evolution. PACE of a chimeric Methanosarcina spp. pyrrolysyl-tRNA synthetase (PylRS) improved its enzymatic efficiency (kcat/KMtRNA) 45-fold compared to the parent enzyme. Transplantation of the evolved mutations into other PylRS-derived synthetases improved yields of proteins containing non-canonical residues up to 9.7-fold. Simultaneous positive and negative selection PACE over 48 h greatly improved the selectivity of a promiscuous Methanocaldococcus jannaschii tyrosyl-tRNA synthetase variant for site-specific incorporation of p-iodo-L-phenylalanine. These findings offer new AARSs that increase the utility of orthogonal translation systems and establish the capability of PACE to efficiently evolve orthogonal AARSs with high activity and amino acid specificity. PMID:29035361

Digital micromirror based near-infrared illumination system for plasmonic photothermal neuromodulation

PubMed Central

Jung, Hyunjun; Kang, Hongki; Nam, Yoonkey

2017-01-01

Light-mediated neuromodulation techniques provide great advantages to investigate neuroscience due to its high spatial and temporal resolution. To generate a spatial pattern of neural activity, it is necessary to develop a system for patterned-light illumination to a specific area. Digital micromirror device (DMD) based patterned illumination system have been used for neuromodulation due to its simple configuration and design flexibility. In this paper, we developed a patterned near-infrared (NIR) illumination system for region specific photothermal manipulation of neural activity using NIR-sensitive plasmonic gold nanorods (GNRs). The proposed system had high power transmission efficiency for delivering power density up to 19 W/mm2. We used a GNR-coated microelectrode array (MEA) to perform biological experiments using E18 rat hippocampal neurons and showed that it was possible to inhibit neural spiking activity of specific area in neural circuits with the patterned NIR illumination. This patterned NIR illumination system can serve as a promising neuromodulation tool to investigate neuroscience in a wide range of physiological and clinical applications. PMID:28663912

High specific energy, high capacity nickel-hydrogen cell design

NASA Technical Reports Server (NTRS)

Wheeler, James R.

1993-01-01

A 3.5 inch rabbit-ear-terminal nickel-hydrogen cell was designed and tested to deliver high capacity at steady discharge rates up to and including a C rate. Its specific energy yield of 60.6 wh/kg is believed to be the highest yet achieved in a slurry-process nickel-hydrogen cell, and its 10 C capacity of 113.9 AH the highest capacity yet of any type in a 3.5 inch diameter size. The cell also demonstrated a pulse capability of 180 amps for 20 seconds. Specific cell parameters and performance are described. Also covered is an episode of capacity fading due to electrode swelling and its successful recovery by means of additional activation procedures.

Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves

PubMed Central

von Ellenrieder, Nicolás; Ferrari-Marinho, Taissa; Avoli, Massimo; Dubeau, François; Gotman, Jean

2015-01-01

Epileptic discharges in focal epilepsy are frequently activated during non-rapid eye movement sleep. Sleep slow waves are present during this stage and have been shown to include a deactivated (‘down’, hyperpolarized) and an activated state (‘up’, depolarized). The ‘up’ state enhances physiological rhythms, and we hypothesize that sleep slow waves and particularly the ‘up’ state are the specific components of non-rapid eye movement sleep that mediate the activation of epileptic activity. We investigated eight patients with pharmaco-resistant focal epilepsies who underwent combined scalp-intracerebral electroencephalography for diagnostic evaluation. We analysed 259 frontal electroencephalographic channels, and manually marked 442 epileptic spikes and 8487 high frequency oscillations during high amplitude widespread slow waves, and during matched control segments with low amplitude widespread slow waves, non-widespread slow waves or no slow waves selected during the same sleep stages (total duration of slow wave and control segments: 49 min each). During the slow waves, spikes and high frequency oscillations were more frequent than during control segments (79% of spikes during slow waves and 65% of high frequency oscillations, both P ∼ 0). The spike and high frequency oscillation density also increased for higher amplitude slow waves. We compared the density of spikes and high frequency oscillations between the ‘up’ and ‘down’ states. Spike and high frequency oscillation density was highest during the transition from the ‘up’ to the ‘down’ state. Interestingly, high frequency oscillations in channels with normal activity expressed a different peak at the transition from the ‘down’ to the ‘up’ state. These results show that the apparent activation of epileptic discharges by non-rapid eye movement sleep is not a state-dependent phenomenon but is predominantly associated with specific events, the high amplitude widespread slow waves that are frequent, but not continuous, during this state of sleep. Both epileptic spikes and high frequency oscillations do not predominate, like physiological activity, during the ‘up’ state but during the transition from the ‘up’ to the ‘down’ state of the slow wave, a period of high synchronization. Epileptic discharges appear therefore more associated with synchronization than with excitability. Furthermore, high frequency oscillations in channels devoid of epileptic activity peak differently during the slow wave cycle from those in channels with epileptic activity. This property may allow differentiating physiological from pathological high frequency oscillations, a problem that is unresolved until now. PMID:25792528

A Novel Detection Model and Its Optimal Features to Classify Falls from Low- and High-Acceleration Activities of Daily Life Using an Insole Sensor System

PubMed Central

Cates, Benjamin; Sim, Taeyong; Heo, Hyun Mu; Kim, Bori; Kim, Hyunggun; Mun, Joung Hwan

2018-01-01

In order to overcome the current limitations in current threshold-based and machine learning-based fall detectors, an insole system and novel fall classification model were created. Because high-acceleration activities have a high risk for falls, and because of the potential damage that is associated with falls during high-acceleration activities, four low-acceleration activities, four high-acceleration activities, and eight types of high-acceleration falls were performed by twenty young male subjects. Encompassing a total of 800 falls and 320 min of activities of daily life (ADLs), the created Support Vector Machine model’s Leave-One-Out cross-validation provides a fall detection sensitivity (0.996), specificity (1.000), and accuracy (0.999). These classification results are similar or superior to other fall detection models in the literature, while also including high-acceleration ADLs to challenge the classification model, and simultaneously reducing the burden that is associated with wearable sensors and increasing user comfort by inserting the insole system into the shoe. PMID:29673165

Structure-Function Relationships in Human Testis-determining Factor SRY

PubMed Central

Racca, Joseph D.; Chen, Yen-Shan; Maloy, James D.; Wickramasinghe, Nalinda; Phillips, Nelson B.; Weiss, Michael A.

2014-01-01

Human testis determination is initiated by SRY, a Y-encoded architectural transcription factor. Mutations in SRY cause 46 XY gonadal dysgenesis with female somatic phenotype (Swyer syndrome) and confer a high risk of malignancy (gonadoblastoma). Such mutations cluster in the SRY high mobility group (HMG) box, a conserved motif of specific DNA binding and bending. To explore structure-function relationships, we constructed all possible substitutions at a site of clinical mutation (W70L). Our studies thus focused on a core aromatic residue (position 15 of the consensus HMG box) that is invariant among SRY-related HMG box transcription factors (the SOX family) and conserved as aromatic (Phe or Tyr) among other sequence-specific boxes. In a yeast one-hybrid system sensitive to specific SRY-DNA binding, the variant domains exhibited reduced (Phe and Tyr) or absent activity (the remaining 17 substitutions). Representative nonpolar variants with partial or absent activity (Tyr, Phe, Leu, and Ala in order of decreasing side-chain volume) were chosen for study in vitro and in mammalian cell culture. The clinical mutation (Leu) was found to markedly impair multiple biochemical and cellular activities as respectively probed through the following: (i) in vitro assays of specific DNA binding and protein stability, and (ii) cell culture-based assays of proteosomal degradation, nuclear import, enhancer DNA occupancy, and SRY-dependent transcriptional activation. Surprisingly, however, DNA bending is robust to this or the related Ala substitution that profoundly impairs box stability. Together, our findings demonstrate that the folding, trafficking, and gene-regulatory function of SRY requires an invariant aromatic “buttress” beneath its specific DNA-bending surface. PMID:25258310

High power density supercapacitors based on the carbon dioxide activated D-glucose derived carbon electrodes and 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid

NASA Astrophysics Data System (ADS)

Tooming, T.; Thomberg, T.; Kurig, H.; Jänes, A.; Lust, E.

2015-04-01

The electrochemical impedance spectroscopy, cyclic voltammetry, constant current charge/discharge and the constant power discharge methods have been applied to establish the electrochemical characteristics of the electrical double-layer capacitor (EDLC) consisting of the 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF4) ionic liquid and microporous carbon electrodes. Microporous carbon material used for preparation of electrodes (GDAC - glucose derived activated carbon), has been synthesised from D-(+)-glucose by the hydrothermal carbonization method, including subsequent pyrolysis, carbon dioxide activation and surface cleaning step with hydrogen. The Brunauer-Emmett-Teller specific surface area (SBET = 1540 m2 g-1), specific surface area calculated using the non-local density functional theory in conjunction with stable adsorption integral equation using splines (SAIEUS) model SSAIEUS = 1820 m2 g-1, micropore surface area (Smicro = 1535 m2 g-1), total pore volume (Vtot = 0.695 cm3 g-1) and the pore size distribution were obtained from the N2 sorption data. The SBET, Smicro and Vtot values have been correlated with the electrochemical characteristics strongly dependent on the carbon activation conditions applied for EDLCs. Wide region of ideal polarizability (ΔV ≤ 3.2 V), very short charging/discharging time constant (2.7 s), and high specific series capacitance (158 F g-1) have been calculated for the optimized carbon material GDAC-10h (activation of GDAC with CO2 during 10 h) in EMImBF4 demonstrating that this system can be used for completing the EDLC with high energy- and power densities.

Production of activated carbon from rice husk Vietnam

NASA Astrophysics Data System (ADS)

Korobochkin, V. V.; Tu, N. V.; Hieu, N. M.

2016-09-01

This work is dedicated to the production of activated carbon from rice husk from Delta of the Red River in Viet Nam. At the first stage, carbonization of a rice husk was carried out to obtain material containing 43.1% carbon and 25 % silica with a specific surface area of 51.5 m2/g. After separating of silica (the second stage), the specific surface area of the product increased to 204 m2/g and the silica content decreased to 1.23% by weight as well. The most important stage in the formation of the porous structure of the material is the activation. The products with the high specific surface area in the range of 800-1345 m2/g were obtained by activation of carbonized product with water vapour or carbon dioxide at temperatures of 700 °C and 850 °C, with varying the flow rate of the activating agent and activation time. The best results were achieved by activation of carbon material with water vapour at the flow rate of 0.08 dm3/min per 500 g of material and the temperature of 850 °C.

NASA's Hall Thruster Program 2002

NASA Technical Reports Server (NTRS)

Jankovsky, Robert S.; Jacobson, David T.; Pinero, Luis R.; Manzella, David H.; Hofer, Richard R.; Peterson, Peter Y.

2002-01-01

The NASA Hall thruster program currently supports a number of tasks related to high power thruster development for a number of customers including the Energetics Program (formerly called the Space-based Program), the Space Solar Power Program, and the In-space Propulsion Program. In program year 2002, two tasks were central to the NASA Hall thruster program: 1) the development of a laboratory Hall thruster capable of providing high thrust at high power-, and 2) investigations into operation of Hall thrusters at high specific impulse. In addition to these two primary thruster development activities, there are a number of other on-going activities supported by the NASA Hall thruster program. These additional activities are related to issues such as high-power power processor architecture, thruster lifetime, and spacecraft integration.

Tuberculin-Specific T Cells Are Reduced in Active Pulmonary Tuberculosis Compared to LTBI or Status Post BCG Vaccination

PubMed Central

Streitz, Mathias; Fuhrmann, Stephan; Powell, Fiona; Quassem, Ali; Nomura, Laurel; Maecker, Holden; Martus, Peter; Volk, Hans-Dieter

2011-01-01

Functional characteristics of tuberculosis (TB)–specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone. PMID:21186260

Spatial accessibility to specific sport facilities and corresponding sport practice: the RECORD Study.

PubMed

Karusisi, Noëlla; Thomas, Frédérique; Méline, Julie; Chaix, Basile

2013-04-20

Physical activity is considered as a major component of a healthy lifestyle. However, few studies have examined the relationships between the spatial accessibility to sport facilities and sport practice with a sufficient degree of specificity. The aim of this study was to investigate the associations between the spatial accessibility to specific types of sports facilities and the practice of the corresponding sports after carefully controlling for various individual socio-demographic characteristics and neighborhood socioeconomic variables. Data from the RECORD Study involving 7290 participants recruited in 2007-2008, aged 30-79 years, and residing in the Paris metropolitan area were analyzed. Four categories of sports were studied: team sports, racket sports, swimming and related activities, and fitness. Spatial accessibility to sport facilities was measured with two complementary approaches that both take into account the street network (distance to the nearest facility and count of facilities around the dwelling). Associations between the spatial accessibility to sport facilities and the practice of the corresponding sports were assessed using multilevel logistic regression after adjusting for individual and contextual characteristics. High individual education and high household income were associated with the practice of racket sports, swimming or related activities, and fitness over the previous 7 days. The spatial accessibility to swimming pools was associated with swimming and related sports, even after adjustment for individual/contextual factors. The spatial accessibility to facilities was not related to the practice of other sports. High neighborhood income was associated with the practice of a racket sport and fitness. Accessibility is a multi-dimensional concept that integrates educational, financial, and geographical aspects. Our work supports the evidence that strategies to increase participation in sport activities should improve the spatial and financial access to specific facilities, but also address educational disparities in sport practice.

Structural and kinetic studies of a novel nerol dehydrogenase from Persicaria minor, a nerol-specific enzyme for citral biosynthesis.

PubMed

Tan, Cheng Seng; Hassan, Maizom; Mohamed Hussein, Zeti Azura; Ismail, Ismanizan; Ho, Kok Lian; Ng, Chyan Leong; Zainal, Zamri

2018-02-01

Geraniol degradation pathway has long been elucidated in microorganisms through bioconversion studies, yet weakly characterised in plants; enzyme with specific nerol-oxidising activity has not been reported. A novel cDNA encodes nerol dehydrogenase (PmNeDH) was isolated from Persicaria minor. The recombinant PmNeDH (rPmNeDH) is a homodimeric enzyme that belongs to MDR (medium-chain dehydrogenases/reductases) superfamily that catalyses the first oxidative step of geraniol degradation pathway in citral biosynthesis. Kinetic analysis revealed that rPmNeDH has a high specificity for allylic primary alcohols with backbone ≤10 carbons. rPmNeDH has ∼3 fold higher affinity towards nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) than its trans-isomer, geraniol. To our knowledge, this is the first alcohol dehydrogenase with higher preference towards nerol, suggesting that nerol can be effective substrate for citral biosynthesis in P. minor. The rPmNeDH crystal structure (1.54 Å) showed high similarity with enzyme structures from MDR superfamily. Structure guided mutation was conducted to describe the relationships between substrate specificity and residue substitutions in the active site. Kinetics analyses of wild-type rPmNeDH and several active site mutants demonstrated that the substrate specificity of rPmNeDH can be altered by changing any selected active site residues (Asp 280 , Leu 294 and Ala 303 ). Interestingly, the L294F, A303F and A303G mutants were able to revamp the substrate preference towards geraniol. Furthermore, mutant that exhibited a broader substrate range was also obtained. This study demonstrates that P. minor may have evolved to contain enzyme that optimally recognise cis-configured nerol as substrate. rPmNeDH structure provides new insights into the substrate specificity and active site plasticity in MDR superfamily. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

PubMed Central

van Norren, K; Kegler, D; Argilés, J M; Luiking, Y; Gorselink, M; Laviano, A; Arts, K; Faber, J; Jansen, H; van der Beek, E M; van Helvoort, A

2009-01-01

Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6–7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumour-bearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (P<0.02)) and improved muscle performance (loss of max force reduced to 55–64% of TB-con (P<0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (P<0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided. PMID:19259092

Cortical lamina-dependent blood volume changes in human brain at 7 T.

PubMed

Huber, Laurentius; Goense, Jozien; Kennerley, Aneurin J; Trampel, Robert; Guidi, Maria; Reimer, Enrico; Ivanov, Dimo; Neef, Nicole; Gauthier, Claudine J; Turner, Robert; Möller, Harald E

2015-02-15

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

At-Home Activities for Reading, Language Arts, and Social Studies. Over 100 Activities To Increase Children's Love of Learning.

ERIC Educational Resources Information Center

Spizman, Robyn Freedman; Garber, Marianne Daniels

Linking home and school, this book presents over 100 activities for grades K-3 that utilize things at parents' fingertips which will enhance their children's learning. Each low-maintenance, high-interest activity in the book teaches a specific skill and integrates math, science, social studies, and language arts so that learning is purposeful and…

Isolation, purification and characterization of β-amylase from Dioscorea hispida Dennst

NASA Astrophysics Data System (ADS)

Oktiarni, Dwita; Lusiana, Simamora, Febri Yanti; Gaol, Jusni M. Lumban

2015-09-01

β-amylase (E.C 3.2.1.2) is an enzyme commonly found in plants and bacteria. The enzyme is an exo-acting carbohydrolase which hydrolyzes α-1.4-glucosidic linkages of starch, removing maltose units from the non-reducing end of the polysaccharide chain, producing β-maltose and β-limit dextrin as the final product. β-amylase is widely distributed in the higher plants such as sweet potato. Besides the use in starch hydrolysis, starch-converting enzymes are also used in a number of other industrial applications, such as laundry and porcelain detergents or as anti-stalling agents in baking. This enzyme was extracted from Dioscorea hispida Dennst in 0.05 M acetate buffer pH 4.8 and followed by ammonium sulfate fractionation at cold temperature (10°C). Ammonium sulfate fractionation was shared into fraction of 0-60%, 60-70%, 70-80% and 80-100%. The fraction containing high of specific activity (determined by Somogyi-Nelson and Lowry methods) was futher purified by dialysis. Fraction with high enzyme activity of β-amylase were fraction 60-70% and 70-80%, with specific activity of Dioscorea hispida Dennst were 1.32 and 1.55 mg sugar.mg protein-1.minute-1, whereas specific activity of crude extract enzyme was 0.21 mg sugar.mg protein-1.minute-1. After purified with dialysis, fraction with high enzyme activity of β-amylase were fraction of 60-70% and 70-80%, with specific activity of Dioscorea hispida Dennst was 2.72 and 4.24 mg sugar.mg protein-1.minute-1. The purified Dioscorea hispida Dennst β-amylase from dialysis showed increasing in spesific activity the crude enzyme as much as 24 folds. The characterization of enzyme showed that Dioscorea hispida Dennst derived enzyme had optimum pH of 5.5 and temperature of 70°C. The kinetic parameters of purified Dioscorea hispida Dennst β-amylase showed that the KMapp, Vmaxapp value and Hill constant were 0.0211 mg/ml, 9.63 mg sugar.minute-1 and 1.34, respectively.

Effect of high hydrostatic pressure treatment on isoquercetin production from rutin by commercial α-L-rhamnosidase.

PubMed

Kim, Do-Yeon; Yeom, Soo-Jin; Park, Chang-Su; Kim, Yeong-Su

2016-10-01

To optimize conversion of rutin to isoquercetin by commercial α-L-rhamnosidase using high hydrostatic pressure (HHP). The de-rhamnosylation activity of α-L-rhamnosidase for isoquercetin production was maximal at pH 6.0 and 50 °C using HHP (150 MPa). The enzyme showed high specificity for rutin. The specific activity for rutin at HHP was 1.5-fold higher than that at atmospheric pressure. The enzyme completely hydrolysed 20 mM rutin in tartary buckwheat extract after 2 h at HHP, with a productivity of 10 mM h(-1). The productivity and conversion were 2.2- and 1.5-fold higher at HHP than at atmospheric pressure, respectively. This is the first report concerning the enzymatic hydrolysis of isoquercetin in tartary buckwheat at HHP.

Understanding Threshold Effects of Organized Activity Involvement in Adolescents: Sex and Family Income as Moderators

ERIC Educational Resources Information Center

Randall, Edin T.; Bohnert, Amy M.

2012-01-01

The current study examined the curvilinear links between involvement in organized activities (OA) and sport activities specifically and various indicators of psychological and social development. Participants included 150 9th and 10th graders (57% females) from an urban, selective-enrollment high school. Eligibility for admission is based on city…

The Relationship between Fundamental Movement Skills and Self-Reported Physical Activity during Finnish Junior High School

ERIC Educational Resources Information Center

Jaakkola, Timo; Washington, Tracy

2013-01-01

Background: Previous studies have shown that fundamental movement skills (FMS) and physical activity are related. Specifically, earlier studies have demonstrated that the ability to perform a variety of FMS increases the likelihood of children participating in a range of physical activities throughout their lives. To date, however, there have not…

Active vs. Reactive Threat Responding is Associated with Differential c-Fos Expression in Specific Regions of Amygdala and Prefrontal Cortex

ERIC Educational Resources Information Center

Martinez, Raquel C. R.; Gupta, Nikita; Lazaro-Munoz, Gabriel; Sears, Robert M.; Kim, Soojeong; Moscarello, Justin M.; LeDoux, Joseph E.; Cain, Christopher K.

2013-01-01

Active avoidance (AA) is an important paradigm for studying mechanisms of aversive instrumental learning, pathological anxiety, and active coping. Unfortunately, AA neurocircuits are poorly understood, partly because behavior is highly variable and reflects a competition between Pavlovian reactions and instrumental actions. Here we exploited the…

Lessons learned from a highly-active CD22-specific chimeric antigen receptor.

PubMed

Long, Adrienne H; Haso, Waleed M; Orentas, Rimas J

2013-04-01

CD22 is an attractive target for the development of immunotherapeutic approaches for the therapy of B-cell malignancies. In particular, an m971 antibody-derived, second generation chimeric antigen receptor (CAR) that targets CD22 holds significant therapeutic promise. The key aspect for the development of such a highly-active CAR was its ability to target a membrane-proximal epitope of CD22.

Small-molecule inhibitors of phosphatidylcholine transfer protein/StarD2 identified by high-throughput screening.

PubMed

Wagle, Neil; Xian, Jun; Shishova, Ekaterina Y; Wei, Jie; Glicksman, Marcie A; Cuny, Gregory D; Stein, Ross L; Cohen, David E

2008-12-01

Phosphatidylcholine transfer protein (PC-TP, also referred to as StarD2) is a highly specific intracellular lipid-binding protein that catalyzes the transfer of phosphatidylcholines between membranes in vitro. Recent studies have suggested that PC-TP in vivo functions to regulate fatty acid and glucose metabolism, possibly via interactions with selected other proteins. To begin to address the relationship between activity in vitro and biological function, we undertook a high-throughput screen to identify small-molecule inhibitors of the phosphatidylcholine transfer activity of PC-TP. After adapting a fluorescence quench assay to measure phosphatidylcholine transfer activity, we screened 114,752 compounds of a small-molecule library. The high-throughput screen identified 14 potential PC-TP inhibitors. Of these, 6 compounds exhibited characteristics consistent with specific inhibition of PC-TP activity, with IC(50) values that ranged from 4.1 to 95.0muM under conditions of the in vitro assay. These compounds should serve as valuable reagents to elucidate the biological function of PC-TP. Because mice with homozygous disruption of the PC-TP gene (Pctp) are sensitized to insulin action and relatively resistant to the development of atherosclerosis, these inhibitors may also prove to be of value in the management of diabetes and atherosclerotic cardiovascular diseases.

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

PubMed

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

2016-08-01

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

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

PubMed

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

1991-01-01

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

Preparation, characterization, and activity of a peptide-cellulosic aerogel protease sensor from cotton

USDA-ARS?s Scientific Manuscript database

Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties of both high porosity and specific surface area for biosensor design. We report here the preparation, characterization, and activity of a peptide-nanocellulose aerogel (PA) made from unprocessed cot...

Metabotropic Glutamate Receptor 5 Activity in the Nucleus Accumbens Is Required for the Maintenance of Ethanol Self-Administration in a Rat Genetic Model of High Alcohol Intake

PubMed Central

Besheer, Joyce; Grondin, Julie J.M.; Cannady, Reginald; Sharko, Amanda C.; Faccidomo, Sara; Hodge, Clyde W.

2010-01-01

Background Systemic modulation of Group I and II metabotropic glutamate receptors (mGluRs) regulate ethanol self-administration in a variety of animal models. Although these receptors are expressed in reward-related brain regions, the anatomical specificity of their functional involvement in ethanol self-administration remains to be characterized. This study sought to evaluate the functional role of Group I (mGluR5) and Group II (mGluR2/3) in mesocorticolimbic brain regions in ethanol self-administration. Methods Alcohol-preferring (P) rats, a genetic model of high alcohol drinking, were trained to self-administer ethanol (15% v/v) versus water in operant conditioning chambers. Effects of brain site-specific infusion of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and the mGluR2/3 agonist were then assessed on the maintenance of self-administration. Results Microinjection of the mGluR5 antagonist MPEP in the nucleus accumbens reduced ethanol self-administration at a dose that did not alter locomotor activity. By contrast, infusion of the mGluR2/3 agonist LY379268 in the nucleus accumbens reduced self-administration and produced nonspecific reductions in locomotor activity. The mGluR5 involvement showed anatomical specificity as evidenced by lack of effect of MPEP infusion in the dorsomedial caudate or medial prefrontal cortex on ethanol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (.4% w/v) versus water, and effects of intra-accumbens MPEP were tested. The MPEP did not alter sucrose self-administration or motor behavior. Conclusions These results suggest that mGluR5 activity specifically in the nucleus accumbens is required for the maintenance of ethanol self-administration in individuals with genetic risk for high alcohol consumption. PMID:19897175

Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake.

PubMed

Besheer, Joyce; Grondin, Julie J M; Cannady, Reginald; Sharko, Amanda C; Faccidomo, Sara; Hodge, Clyde W

2010-05-01

Systemic modulation of Group I and II metabotropic glutamate receptors (mGluRs) regulate ethanol self-administration in a variety of animal models. Although these receptors are expressed in reward-related brain regions, the anatomical specificity of their functional involvement in ethanol self-administration remains to be characterized. This study sought to evaluate the functional role of Group I (mGluR5) and Group II (mGluR2/3) in mesocorticolimbic brain regions in ethanol self-administration. Alcohol-preferring (P) rats, a genetic model of high alcohol drinking, were trained to self-administer ethanol (15% v/v) versus water in operant conditioning chambers. Effects of brain site-specific infusion of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and the mGluR2/3 agonist were then assessed on the maintenance of self-administration. Microinjection of the mGluR5 antagonist MPEP in the nucleus accumbens reduced ethanol self-administration at a dose that did not alter locomotor activity. By contrast, infusion of the mGluR2/3 agonist LY379268 in the nucleus accumbens reduced self-administration and produced nonspecific reductions in locomotor activity. The mGluR5 involvement showed anatomical specificity as evidenced by lack of effect of MPEP infusion in the dorsomedial caudate or medial prefrontal cortex on ethanol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (.4% w/v) versus water, and effects of intra-accumbens MPEP were tested. The MPEP did not alter sucrose self-administration or motor behavior. These results suggest that mGluR5 activity specifically in the nucleus accumbens is required for the maintenance of ethanol self-administration in individuals with genetic risk for high alcohol consumption. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Bioreactor Transient Exposure Activates Specific Neurotrophic Pathway in Cortical Neurons

NASA Astrophysics Data System (ADS)

Zimmitti, V.; Benedetti, E.; Caracciolo, V.; Sebastiani, P.; Di Loreto, S.

2010-02-01

Altered gravity forces might influence neuroplasticity and can provoke changes in biochemical mechanisms. In this contest, neurotrophins have a pivotal role, particularly nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). A suspension of dissociated cortical cells from rat embryos was exposed to 24 h of microgravity before plating in normal adherent culture system. Expression and transductional signalling pathways of NGF and BDNF were assessed at the end of maturational process (8-10 days in vitro). Rotating wall vessel bioreactor (RWV) pre-exposition did not induce changes in NGF expression and its high affinity receptor TrkA. On the contrary both BDNF expression and its high affinity receptor TrkB were strongly up-regulated, inducing Erk-5, but not Erk-1/2 activation and, in turn, MEF2C over-expression and activation. According to our previous and present results, we postulate that relatively short microgravitational stimuli, applied to neural cells during the developmental stage, exert a long time activation of specific neurotrophic pathways.

Discovery of antimicrobial compounds targeting bacterial type FAD synthetases.

PubMed

Sebastián, María; Anoz-Carbonell, Ernesto; Gracia, Begoña; Cossio, Pilar; Aínsa, José Antonio; Lans, Isaías; Medina, Milagros

2018-12-01

The increase of bacterial strains resistant to most of the available antibiotics shows a need to explore novel antibacterial targets to discover antimicrobial drugs. Bifunctional bacterial FAD synthetases (FADSs) synthesise the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors act in vital processes as part of flavoproteins, making FADS an essential enzyme. Bacterial FADSs are potential antibacterial targets because of differences to mammalian enzymes, particularly at the FAD producing site. We have optimised an activity-based high throughput screening assay targeting Corynebacterium ammoniagenes FADS (CaFADS) that identifies inhibitors of its different activities. We selected the three best high-performing inhibitors of the FMN:adenylyltransferase activity (FMNAT) and studied their inhibition mechanisms and binding properties. The specificity of the CaFADS hits was evaluated by studying also their effect on the Streptococcus pneumoniae FADS activities, envisaging differences that can be used to discover species-specific antibacterial drugs. The antimicrobial effect of these compounds was also evaluated on C. ammoniagenes, S. pneumoniae, and Mycobacterium tuberculosis cultures, finding hits with favourable antimicrobial properties.

Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impacts viral set point

PubMed Central

Ndhlovu, Zaza; Kamya, Philomena; Mewalal, Nikoshia; Kløverpris, Henrik N.; Nkosi, Thandeka; Pretorius, Karyn; Laher, Faatima; Ogunshola, Funsho; Chopera, Denis; Shekhar, Karthik; Ghebremichael, Musie; Ismail, Nasreen; Moodley, Amber; Malik, Amna; Leslie, Alasdair; Goulder, Philip J.R; Buus, Søren; Chakraborty, Arup; Dong, Krista; Ndung’u, Thumbi; Walker, Bruce D.

2015-01-01

Summary CD8+ T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified twelve hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8+ T cell response, with limited bystander activation of non-HIV memory CD8+ T cells. HIV-specific CD8+ T cells secreted little interferon-γ, underwent rapid apoptosis and failed to upregulate the interleukin 7 receptor, known to be important for T cell survival. The rapidity to peak CD8+ T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8+ T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design. PMID:26362266

Electrodeposition of nickel sulfide on graphene-covered make-up cotton as a flexible electrode material for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Li, Yiju; Ye, Ke; Cheng, Kui; Yin, Jinling; Cao, Dianxue; Wang, Guiling

2015-01-01

In this report, graphene nanosheets (GNS)/nickel sulfide (NiS) based material for high-performance supercapacitor is prepared by "dip and dry" and electrodeposition methods. Commercial flexible make-up cottons (MCs) are chose as skeletons to construct homogeneous three-dimensional (3D) interconnected graphene-wrapped macro-networks, which can support structures for high loading of active electrode materials and facilitate the access of electrolytes to active electrode materials. The hybrid GNS/NiS based MCs (denoted as MCs@GNS@NiS) electrode yields relatively high specific capacitance of 775 F g-1 at a charge/discharge specific current of 0.5 A g-1 and good capacitance retention of 88.1% after 1000 cycles at 2 A g-1. Furthermore, the MCs@GNS@NiS electrode delivers a high energy density of 11.2 Wh kg-1 at even a high power density of 1008 W kg-1. Therefore, such low-cost and high-performance energy MCs based on GNS/NiS hierarchical nanostructures offer great promise in large-scale energy storage device applications.

Design and applications of biomimetic anthraquinone dyes. Purification of calf intestinal alkaline phosphatase with immobilised terminal ring analogues of C.I. reactive blue 2.

PubMed

Lindner, N M; Jeffcoat, R; Lowe, C R

1989-06-28

A 330-fold one-step purification of alkaline phosphatase from a crude calf intestinal extract has been achieved using specific elution with inorganic phosphate (5 mM) from a purpose designed adsorbent comprising a terminal ring phosphonate analogue of C.I. Reactive Blue 2 coupled to Sepharose CL-6B-200. The resulting alkaline phosphatase preparation displayed a specific activity in excess of 1000 U/mg and was of equivalent purity to commercial "high purity" preparations as deduced by sodium dodecyl sulphate polyacrylamide gel electrophoresis and specific activity comparisons.

Roles of s3 site residues of nattokinase on its activity and substrate specificity.

PubMed

Wu, Shuming; Feng, Chi; Zhong, Jin; Huan, Liandong

2007-09-01

Nattokinase (Subtilisin NAT, NK) is a bacterial serine protease with high fibrinolytic activity. To probe their roles on protease activity and substrate specificity, three residues of S3 site (Gly(100), Ser(101) and Leu(126)) were mutated by site-directed mutagenesis. Kinetics parameters of 20 mutants were measured using tetrapeptides as substrates, and their fibrinolytic activities were determined by fibrin plate method. Results of mutation analysis showed that Gly(100) and Ser(101) had reverse steric and electrostatic effects. Residues with bulky or positively charged side chains at position 100 decreased the substrate binding and catalytic activity drastically, while residues with the same characters at position 101 could obviously enhance protease and fibrinolytic activity of NK. Mutation of Leu(126) might impair the structure of the active cleft and drastically decreased the activity of NK. Kinetics studies of the mutants showed that S3 residues were crucial to keep protease activity while they moderately affected substrate specificity of NK. The present study provided some original insight into the P3-S3 interaction in NK and other subtilisins, as well as showed successful protein engineering cases to improve NK as a potential therapeutic agent.

Frequency distribution of specific activities and radiological hazard assessment in surface beach sand samples collected in Bangsaen beach in Chonburi province, Thailand

NASA Astrophysics Data System (ADS)

Changkit, N.; Boonkrongcheep, R.; Youngchauy, U.; Polthum, S.; Kessaratikoon, P.

2017-09-01

The specific activities of natural radionuclides (40K, 226Ra and 232Th) in 50 surface beach sand samples collected from Bangsaen beach in Chonburi province in the easthern region of Thailand, were measured and evaluated. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system in the special laboratory at Thailand Institute of Nuclear Technology (Public Organization). The IAEA-SOIL-375 reference material was used to analyze the concentration of 40K, 226Ra and 232Th in all samples. It was found that the specific activities of 40K, 226Ra and 232Th were ranged from 510.85 - 771.35, 8.17 - 17.06 and 4.25 - 15.68 Bq/kg. Furthermore, frequency distribution of the specific activities were studied, analyzed and found to be the asymmetrical distribution by using a statistical computer program. Moreover, four radiological hazard indices for the investigated area were also calculated by using the median values of specific activities of 40K, 226Ra and 232Th. The results were also compared with the Office of Atoms for Peace (OAP) annual report data, Thailand and global radioactivity measurement and evaluations.

Characterization and organic electric-double-layer-capacitor application of KOH activated coal-tar-pitch-based carbons: Effect of carbonization temperature

NASA Astrophysics Data System (ADS)

Choi, Poo Reum; Lee, Eunji; Kwon, Soon Hyung; Jung, Ji Chul; Kim, Myung-Soo

2015-12-01

The present study reports the influence of pre-carbonization on the properties of KOH-activated coal tar pitch (CTP). The change of crystallinity and pore structure of pre-carbonized CTPs as well as their activated carbons (ACs) as function of pre-carbonization temperature are investigated. The crystallinity of pre-carbonized CTPs increases with increasing the carbonization temperature up to 600 °C, but a disorder occurs during the carbonization around 700 °C and an order happens gradually with increasing the carbonization temperatures in range of 800-1000 °C. The CTPs pre-carbonized at high temperatures are more difficult to be activated with KOH than those pre-carbonized at low temperatures due to the increase of micro-crystalline size and the decrease of surface functional groups. The micro-pores and meso-pores are well developed at around 1.0 nm and 2.4 nm, respectively, as the ACs are pre-carbonized at temperatures of 500-600 °C, exhibiting high specific capacitances as electrode materials for electric double layer capacitor (EDLC). Although the specific surface area (SSA) and pore volume of ACs pre-carbonized at temperatures of 900-1000 °C are extraordinary low (non-porous) as compared to those of AC pre-carbonized at 600 °C, their specific capacitances are comparable to each other. The large specific capacitances with low SSA ACs can be attributed to the structural change resulting from the electrochemical activation during the 1st charge above 2.0 V.

Comparison of Activity Profiles and Physiological Demands Between International Rugby Sevens Matches and Training.

PubMed

Higham, Dean G; Pyne, David B; Anson, Judith M; Hopkins, Will G; Eddy, Anthony

2016-05-01

The specificity of contemporary training practices of international rugby sevens players is unknown. We quantified the positional group-specific activity profiles and physiological demands of on-field training activities and compared these with match demands. Twenty-two international matches and 63 rugby-specific training drills were monitored in 25 backs and 17 forwards from a national squad of male rugby sevens players over a 21-month period. Drills were classified into 3 categories: low-intensity skill refining (n = 23 drills, 560 observations), moderate- to high-intensity skill refining (n = 28 drills, 600 observations), and game simulation (n = 12 drills, 365 observations). Movement patterns (via Global Positioning System devices) and physiological load (via heart rate monitors) were recorded for all activities, and the differences between training and matches were quantified using magnitude-based inferential statistics. Distance covered in total and at ≥3.5 m·s, maximal velocity, and frequency of accelerations and decelerations were lower for forwards during competition compared with those for backs by a small but practically important magnitude. No clear positional group differences were observed for physiological load during matches. Training demands exceeded match demands only for frequency of decelerations of forwards during moderate- to high-intensity skill-refining drills and only by a small amount. Accelerations and distance covered at ≥6 m·s were closer to match values for forwards than for backs during all training activities, but training drills consistently fell below the demands of international competition. Coaches could therefore improve physical and physiological specificity by increasing the movement demands and intensity of training drills.

Jasmonate signaling in plant stress responses and development - active and inactive compounds.

PubMed

Wasternack, Claus; Strnad, Miroslav

2016-09-25

Jasmonates (JAs) are lipid-derived signals mediating plant responses to biotic and abiotic stresses and in plant development. Following the elucidation of each step in their biosynthesis and the important components of perception and signaling, several activators, repressors and co-repressors have been identified which contribute to fine-tuning the regulation of JA-induced gene expression. Many of the metabolic reactions in which JA participates, such as conjugation with amino acids, glucosylation, hydroxylation, carboxylation, sulfation and methylation, lead to numerous compounds with different biological activities. These metabolites may be highly active, partially active in specific processes or inactive. Hydroxylation, carboxylation and sulfation inactivate JA signaling. The precursor of JA biosynthesis, 12-oxo-phytodienoic acid (OPDA), has been identified as a JA-independent signaling compound. An increasing number of OPDA-specific processes is being identified. To conclude, the numerous JA compounds and their different modes of action allow plants to respond specifically and flexibly to alterations in the environment. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Zheng, Tianyong; Olson, Daniel G.; Tian, Liang

Clostridium thermocellum and Thermoanaerobacterium saccharolyticumare thermophilic bacteria that have been engineered to produce ethanol from the cellulose and hemicellulose fractions of biomass, respectively. Although engineered strains of T. saccharolyticumproduce ethanol with a yield of 90% of the theoretical maximum, engineered strains ofC. thermocellumproduce ethanol at lower yields (~50% of the theoretical maximum). In the course of engineering these strains, a number of mutations have been discovered in theiradhEgenes, which encode both alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes. To understand the effects of these mutations, theadhEgenes from six strains ofC. thermocellumandT. saccharolyticumwere cloned and expressed inEscherichia coli, the enzymesmore » produced were purified by affinity chromatography, and enzyme activity was measured. In wild-type strains of both organisms, NADH was the preferred cofactor for both ALDH and ADH activities. In high-ethanol-producing (ethanologen) strains ofT. saccharolyticum, both ALDH and ADH activities showed increased NADPH-linked activity. Interestingly, the AdhE protein of the ethanologenic strain ofC. thermocellumhas acquired high NADPH-linked ADH activity while maintaining NADH-linked ALDH and ADH activities at wild-type levels. When single amino acid mutations in AdhE that caused increased NADPH-linked ADH activity were introduced intoC. thermocellumandT. saccharolyticum, ethanol production increased in both organisms. Structural analysis of the wild-type and mutant AdhE proteins was performed to provide explanations for the cofactor specificity change on a molecular level. This work describes the characterization of the AdhE enzyme from different strains ofC. thermocellumandT. saccharolyticum.C. thermocellumandT. saccharolyticumare thermophilic anaerobes that have been engineered to make high yields of ethanol and can solubilize components of plant biomass and ferment the sugars to ethanol. In the course of engineering these strains, several mutations arose in the bifunctional ADH/ALDH protein AdhE, changing both enzyme activity and cofactor specificity. We show that changing AdhE cofactor specificity from mostly NADH linked to mostly NADPH linked resulted in higher ethanol production byC. thermocellumandT. saccharolyticum.« less

Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics.

PubMed

Sripathi, Kamali N; Banáš, Pavel; Réblová, Kamila; Šponer, Jiří; Otyepka, Michal; Walter, Nils G

2015-02-28

The hepatitis delta virus (HDV) is the only known human pathogen whose genome contains a catalytic RNA motif (ribozyme). The overall architecture of the HDV ribozyme is that of a double-nested pseudoknot, with two GU pairs flanking the active site. Although extensive studies have shown that mutation of either wobble results in decreased catalytic activity, little work has focused on linking these mutations to specific structural effects on catalytic fitness. Here we use molecular dynamics simulations based on an activated structure to probe the active site dynamics as a result of wobble pair mutations. In both wild-type and mutant ribozymes, the in-line fitness of the active site (as a measure of catalytic proficiency) strongly depends on the presence of a C75(N3H3+)N1(O5') hydrogen bond, which positions C75 as the general acid for the reaction. Our mutational analyses show that each GU wobble supports catalytically fit conformations in distinct ways; the reverse G25U20 wobble promotes high in-line fitness, high occupancy of the C75(N3H3+)G1(O5') general-acid hydrogen bond and stabilization of the G1U37 wobble, while the G1U37 wobble acts more locally by stabilizing high in-line fitness and the C75(N3H3+)G1(O5') hydrogen bond. We also find that stable type I A-minor and P1.1 hydrogen bonding above and below the active site, respectively, prevent local structural disorder from spreading and disrupting global conformation. Taken together, our results define specific, often redundant architectural roles for several structural motifs of the HDV ribozyme active site, expanding the known roles of these motifs within all HDV-like ribozymes and other structured RNAs.

Wobble Pairs of the HDV Ribozyme Play Specific Roles in Stabilization of Active Site Dynamics

PubMed Central

Sripathi, Kamali N.; Banáš, Pavel; Reblova, Kamila; Šponer, Jiři; Otyepka, Michal

2015-01-01

The hepatitis delta virus (HDV) is the only known human pathogen whose genome contains a catalytic RNA motif (ribozyme). The overall architecture of the HDV ribozyme is that of a double-nested pseudoknot, with two GU pairs flanking the active site. Although extensive studies have shown that mutation of either wobble results in decreased catalytic activity, little work has focused on linking these mutations to specific structural effects on catalytic fitness. Here we use molecular dynamics simulations based on an activated structure to probe the active site dynamics as a result of wobble pair mutations. In both wild-type and mutant ribozymes, the in-line fitness of the active site (as a measure of catalytic proficiency) strongly depends on the presence of a C75(N3H3+)N1(O5′) hydrogen bond, which positions C75 as the general acid for the reaction. Our mutational analyses show that each GU wobble supports catalytically fit conformations in distinct ways; the reverse G25U20 wobble promotes high in-line fitness, high occupancy of the C75(N3H3+)G1(O5′) general-acid hydrogen bond and stabilization of the G1U37 wobble, while the G1U37 wobble acts more locally by stabilizing high in-line fitness and the C75(N3H3+)G1(O5′) hydrogen bond. We also find that stable type I A-minor and P1.1 hydrogen bonding above and below the active site, respectively, prevent local structural disorder from spreading and disrupting global conformation. Taken together, our results define specific, often redundant architectural roles for several structural motifs of the HDV ribozyme active site, expanding the known roles of these motifs within all HDV-like ribozymes and other structured RNAs. PMID:25631765

The development and characterization of an ELISA specifically detecting the active form of cathepsin K.

PubMed

Sun, S; Karsdal, M A; Bay-Jensen, A C; Sørensen, M G; Zheng, Q; Dziegiel, M H; Maksymowych, W P; Henriksen, K

2013-10-01

Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosis or ankylosing spondylitis. Presently there are no robust assays for the assessment of active cathepsin K in serum, and therefore an ELISA specifically detecting the N-terminal of the active form of cathepsin K was developed. The assay was technically robust, with a lowest limit of detection (LOD) of 0.085 ng/mL. The average intra- and inter-assay CV% were 6.60% and 8.56% respectively. The dilution recovery and spike recovery tests in human serum were within 100±20% within the range of the assay. A comparison of latent and active cathepsin K confirmed specificity towards the active form. Quantification of the levels of active cathepsin K in supernatants of purified human osteoclasts compared to corresponding macrophages showed a 30-fold induction (p<0.001). In contrast, in serum samples from osteoporotic women on estrogen or bisphosphonate therapy and from ankylosing spondylitis patients no clinically relevant differences were observed. In summary, we have developed a robust and sensitive assay specifically detecting the active form of cathepsin K; however, while it monitors osteoclasts with high specificity in vitro, it appears that circulating levels of active cathepsin K do not reflect bone changes under these circumstances. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Decoding task-based attentional modulation during face categorization.

PubMed

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

2011-05-01

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

Silencing and heterologous expression of ppo-2 indicate a specific function of a single polyphenol oxidase isoform in resistance of dandelion (Taraxacum officinale) against Pseudomonas syringae pv. tomato.

PubMed

Richter, Carolin; Dirks, Mareike E; Gronover, Christian Schulze; Prüfer, Dirk; Moerschbacher, Bruno M

2012-02-01

Dandelion (Taraxacum officinale) possesses an unusually high degree of disease resistance. As this plant exhibits high polyphenol oxidase (PPO) activity and PPO have been implicated in resistance against pests and pathogens, we analyzed the potential involvement of five PPO isoenzymes in the resistance of dandelion against Botrytis cinerea and Pseudomonas syringae pv. tomato. Only one PPO (ppo-2) was induced during infection, and ppo-2 promoter and β-glucuronidase marker gene fusions revealed strong induction of the gene surrounding lesions induced by B. cinerea. Specific RNAi silencing reduced ppo-2 expression only, and concomitantly increased plant susceptibility to P. syringae pv. tomato. At 4 days postinoculation, P. syringae pv. tomato populations were strongly increased in the ppo-2 RNAi lines compared with wild-type plants. When the dandelion ppo-2 gene was expressed in Arabidopsis thaliana, a plant having no PPO gene, active protein was formed and protein extracts of the transgenic plants exhibited substrate-dependent antimicrobial activity against P. syringae pv. tomato. These results clearly indicate a strong contribution of a specific, single PPO isoform to disease resistance. Therefore, we propose that specific PPO isoenzymes be included in a new family of pathogenesis-related (PR) proteins.

Assessment of nodal involvement in non-small-cell lung cancer with 18F-FDG-PET/CT: mediastinal blood pool cut-off has the highest sensitivity and tumour SUVmax/2 has the highest specificity.

PubMed

Mallorie, Amy; Goldring, James; Patel, Anant; Lim, Eric; Wagner, Thomas

2017-08-01

Lymph node involvement in non-small-cell lung cancer (NSCLC) is a major factor in determining management and prognosis. We aimed to evaluate the accuracy of fluorine-18-fluorodeoxyglucose-PET/computed tomography (CT) for the assessment of nodal involvement in patients with NSCLC. In this retrospective study, we included 61 patients with suspected or confirmed resectable NSCLC over a 2-year period from April 2013 to April 2015. 221 nodes with pathological staging from surgery or endobronchial ultrasound-guided transbronchial needle aspiration were assessed using a nodal station-based analysis with original clinical reports and three different cut-offs: mediastinal blood pool (MBP), liver background and tumour standardized uptake value maximal (SUVmax)/2. Using nodal station-based analysis for activity more than tumour SUVmax/2, the sensitivity was 45%, the specificity was 89% and the negative predictive value (NPV) was 87%. For activity more than MBP, the sensitivity was 93%, the specificity was 72% and NPV was 98%. For activity more than liver background, the sensitivity was 83%, the specificity was 84% and NPV was 96%. Using a nodal staging-based analysis for accuracy at detecting N2/3 disease, for activity more than tumour SUVmax/2, the sensitivity was 59%, the specificity was 85% and NPV was 80%. For activity more than MBP, the sensitivity was 95%, the specificity was 61% and NPV was 96%. For activity more than liver background, the sensitivity was 86%, the specificity was 81% and NPV was 92%. Receiver-operating characteristic analysis showed the optimal nodal SUVmax to be more than 6.4 with a sensitivity of 45% and a specificity of 95%, with an area under the curve of 0.85. Activity more than MBP was the most sensitive cut-off with the highest sensitivity and NPV. Activity more than primary tumour SUVmax/2 was the most specific cut-off. Nodal SUVmax more than 6.4 has a high specificity of 95%.

Influence of caecal microflora and of two dietary protein levels on the adaptation of the exocrine pancreas: comparative study in germ-free and conventional rats.

PubMed

Lhoste, E F; Catala, I; Fiszlewicz, M; Gueugneau, A M; Popot, F; Vaissade, P; Corring, T; Szylit, O

1996-03-01

Dietary proteins are degraded by both endogenous enzymes and the caecal microflora. In conventional rats the enzyme content of the pancreas depends on the amount of dietary protein. The influence of the caecal microflora on this process is unknown. We report here the effect of the caecal microflora on pancreatic enzymes (proteases, amylase (EC 3.2.1.1), lipase (EC 3.1.1.3)) and on colonic metabolites (NH3, urea, short-chain fatty acids). Germ-free and conventional male Fischer rats were fed for 3 weeks with a diet containing 220 or 450 g protein/kg provided as a mixture of fish concentrate and soyabean isolate. The excretion of NH3 and the pH were specifically increased by the high-protein diet in the germ-free rats. The higher production of isobutyrate, valerate and isovalerate in conventional rats fed on the high-protein diet reflected a high bacterial proteolytic activity since these short-chain fatty acids are specific indicators of this activity. The microflora hydrolysed urea to NH3 and maintained the pH at neutrality whatever the amount of protein in the diet since there were changes in germ-free rats but not in conventional ones. In germ-free rats, amylase, trypsin (EC 3.4.21.4), elastase (EC 3.4.21.36) and carboxypeptidase A (EC 3.4.17.1) specific activities were significantly lower than in conventional rats. The adaptation of the pancreas to the 450 g protein/kg diet was not impaired by the bacterial status except for the specific activity of chymotrypsin (EC 3.4.21.1) which was more increased by this diet in germ-free than in conventional rats. Moreover, the specific activity of lipase increased only in conventional rats fed on the 450 g protein/kg diet. In conclusion, we observed a relationship between the enzyme content of the pancreas and the presence or absence of the caecal microflora suggesting that bacterial fermentation influences pancreatic function.

The Natural Protective Mechanism Against Hyperglycemia in Vascular Endothelial Cells

PubMed Central

Riahi, Yael; Sin-Malia, Yoav; Cohen, Guy; Alpert, Evgenia; Gruzman, Arie; Eckel, Juergen; Staels, Bart; Guichardant, Michel; Sasson, Shlomo

2010-01-01

OBJECTIVE Vascular endothelial cells (VECs) downregulate their rate of glucose uptake in response to hyperglycemia by decreasing the expression of their typical glucose transporter GLUT-1. Hitherto, we discovered critical roles for the protein calreticulin and the arachidonic acid–metabolizing enzyme 12-lipoxygenase in this autoregulatory process. The hypothesis that 4-hydroxydodeca-(2E,6Z)-dienal (4-HDDE), the peroxidation product of 12-lipoxygenase, mediates this downregulatory mechanism by activating peroxisome proliferator–activated receptor (PPAR) δ was investigated. RESEARCH DESIGN AND METHODS Effects of 4-HDDE and PPARδ on the glucose transport system and calreticulin expression in primary bovine aortic endothelial cells were evaluated by pharmacological and molecular interventions. RESULTS Using GW501516 (PPARδ agonist) and GSK0660 (PPARδ antagonist), we discovered that high-glucose–induced downregulation of the glucose transport system in VECs is mediated by PPARδ. A PPAR-sensitive luciferase reporter assay in VECs revealed that high glucose markedly increased luciferase activity, while GSK0660 abolished it. High-performance liquid chromatography analysis showed that high-glucose incubation substantially elevated the generation of 4-HDDE in VECs. Treatment of VECs, exposed to normal glucose, with 4-HDDE mimicked high glucose and downregulated the glucose transport system and increased calreticulin expression. Like high glucose, 4-HDDE significantly activated PPARδ in cells overexpressing human PPAR (hPPAR)δ but not hPPARα, -γ1, or -γ2. Moreover, silencing of PPARδ prevented high-glucose–dependent alterations in GLUT-1 and calreticulin expression. Finally, specific binding of PPARδ to a PPAR response element in the promoter region of the calreticulin gene was identified by utilizing a specific chromatin immunoprecipitation assay. CONCLUSIONS Collectively, our data show that 4-HDDE plays a central role in the downregulation of glucose uptake in VECs by activating PPARδ. PMID:20107107

Two classes of receptor specific for sperm-activating peptide III in sand-dollar spermatozoa.

PubMed

Yoshino, K; Suzuki, N

1992-06-15

We characterized receptors specific for sperm-activating peptide III (SAP-III: DSDSAQNLIQ) in spermatozoa of the sand dollar, Clypeaster japonicus, using both binding and cross-linking techniques. Analyses of the data obtained from the equilibrium binding of a radiolabeled SAP-III analogueto C. japonicus spermatozoa, using Klotz, Scatchard and Hill plots, showed the presence of two classes of receptors specific for SAP-III in the spermatozoa. One of the receptors (high-affinity) had a Kd of 3.4 nM and 3.4 x 10(4) binding sites/spermatozoon. The other receptor (low-affinity) had a Kd of 48 nM, with 6.1 x 10(4) binding sites/spermatozoon. The Kd of the high-affinity receptor was comparable to the median effective concentration of the intracellular-pH-increasing activity of SAP-III and that of the low-affinity receptor was comparable to the median effective concentration of the cellular-cGMP-elevating activity of the peptide. In addition, Scatchard and Hill plots of the data suggested the existence of positive cooperativity between the high-affinity members. Similar results were also obtained from a binding experiment using a sperm-membrane fraction prepared from C. japonicus spermatozoa. The incubation of intact spermatozoa or sperm plasma membranes with the radioiodinated SAP-III analogue and a chemical cross-linking reagent, disuccinimidyl suberate, resulted in the radiolabeling of three proteins with molecular masses of 126, 87 and 64 kDa, estimated by SDS/PAGE under reducing conditions.

Microporous carbons derived from melamine and isophthalaldehyde: One-pot condensation and activation in a molten salt medium for efficient gas adsorption.

PubMed

Rehman, Adeela; Park, Soo-Jin

2018-04-17

In the present work, mixture of melamine and isophthalaldehyde undergo simultaneous polymerization, carbonization, and in situ activation in the presence of molten salt media through a single all-in-one route to design microporous carbons with high specific surface areas (~3000 m 2 /g). The effect of the activation temperature and molten salts on the polymerization process and final texture of the carbon was explored. Carbon materials prepared at 700 °C, in the presence of KOH (referred as MIK-700), exhibited a narrower pore-size distribution ~1.05 nm than those prepared in the presence of the eutectic KOH-NaOH mixture (MIKN). Additionally, MIK-700 possesses an optimum micropore volume (1.33 cm 3 /g) along with a high nitrogen content (2.66 wt%), resulting in the excellent CO 2 adsorption capacity of 9.7 mmol/g at 273 K and 1 bar. Similarly, the high specific area and highest total pore volume play an important role in H 2 storage at 77 K, with 4.0 wt% uptake by MIKN-800 (specific surface area and pore volume of 2984 m 2 /g and 1.98 cm 3 /g, respectively.) Thus, the facile one-step solvent-free synthesis and activation strategy is an economically favorable avenue for designing microporous carbons as an efficient gas adsorbents.

High sensitivity and specificity of a new functional flow cytometry assay for clinically significant heparin-induced thrombocytopenia antibodies.

PubMed

Garritsen, H S; Probst-Kepper, M; Legath, N; Eberl, W; Samaniego, S; Woudenberg, J; Schuitemaker, J H N; Kroll, H; Gurney, D A; Moore, G W; Zehnder, J L

2014-04-01

Heparin-induced thrombocytopenia (HIT) is a life-threatening condition, in which the anticoagulant heparin, platelet factor 4 (PF4), and platelet-activating antibodies form complexes with prothrombotic properties. Laboratory tests to support clinical diagnosis are subdivided into functional, platelet activation assays, which lack standardization, or immunological assays, which have moderate specificity toward HIT. In this study, clinical performance of HITAlert, a novel in vitro diagnostic (IVD) registered platelet activation assay, was tested in a large cohort of HIT-suspected patients and compared with immunological assays. From 346 HIT-suspected patients (single center), clinical data including 4T pretest probability results, citrated platelet-poor plasmas, and sera were collected, allowing direct comparison of clinical observations with HITAlert results. HITAlert performance was compared with PF4 IgG ELISA (246 patients, three centers) and PF4 PaGIA (298 patients, single center). HITAlert showed high sensitivity (88.2%) and specificity (99.1%) when compared with clinical diagnosis. Agreement of HITAlert with PF4 ELISA- and PF4 PaGIA-positive patients is low (52.7 and 23.2%, respectively), while agreement with PF4 IgG ELISA- and PF4 PaGIA-negative patients is very high (98.1 and 99.1%, respectively). HITAlert performance is excellent when compared with clinical HIT diagnosis, making it a suitable assay for rapid testing of platelet activation due to anticoagulant therapy. © 2013 John Wiley & Sons Ltd.

A new versatile microarray-based method for high throughput screening of carbohydrate-active enzymes.

PubMed

Vidal-Melgosa, Silvia; Pedersen, Henriette L; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G T

2015-04-03

Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A model to assess lactic acid bacteria aminopeptidase activities in Parmigiano Reggiano cheese during ripening.

PubMed

Gatti, M; De Dea Lindner, J; Gardini, F; Mucchetti, G; Bevacqua, D; Fornasari, M E; Neviani, E

2008-11-01

The aim of this work was to investigate in which phases of ripening of Parmigiano Reggiano cheese lactic acid bacteria aminopeptidases present in cheese extract could be involved in release of free amino acids and to better understand the behavior of these enzymes in physical-chemical conditions that are far from their optimum. In particular, we evaluated 6 different substrates to reproduce broad-specificity aminopeptidase N, broad-specificity aminopeptidase C, glutamyl aminopeptidase A, peptidase with high specificity for leucine and alanine, proline iminopeptidase, and X-prolyl dipeptidyl aminopeptidase activities releasing different N-terminal amino acids. The effects of pH, NaCl concentration, and temperature on the enzyme activities of amino acid beta-naphthylamide (betaNA)-substrates were determined by modulating the variables in 19 different runs of an experimental design, which allowed the building of mathematical models able to assess the effect on aminopeptidases activities over a range of values, obtained with bibliographic data, covering different environmental conditions in different zones of the cheese wheel at different aging times. The aminopeptidases tested in this work were present in cell-free Parmigiano Reggiano cheese extract after a 17-mo ripening and were active when tested in model system. The modeling approach shows that to highlight the individual and interactive effects of chemical-physical variables on enzyme activities, it is helpful to determine the true potential of an amino-peptidase in cheese. Our results evidenced that the 6 different lactic acid bacteria peptidases participate in cheese proteolysis and are induced or inhibited by the cheese production parameters that, in turn, depend on the cheese dimension. Generally, temperature and pH exerted the more relevant effects on the enzymatic activities, and in many cases, a relevant interactive effect of these variables was observed. Increasing salt concentration slowed down broad-specificity amino-peptidase C, glutamyl aminopeptidase A, proline iminopeptidase, and peptidase with high specificity for leucine and alanine. Interestingly, this variable did not affect broad-specificity aminopeptidase N and positively affected X-prolyl dipeptidyl aminopeptidase. The models elaborated varying pH, temperatures, and salt concentration and were a useful, low cost, and fast tool to understand the role of the main peptidases in the different phases of cheese ripening in relation to the major environmental factors influencing enzyme activity.

Sports Activity after Low-contact-stress Total Knee Arthroplasty – A long term follow-up study

PubMed Central

Vielgut, Ines; Leitner, Lukas; Kastner, Norbert; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

2016-01-01

The purpose of this study was to provide comprehensive long-term data about sports activity levels in patients following total knee arthroplasty (TKA) and to determine the impact of pre-operative function, pain and specific performed sports on the results. 236 patients who have undergone TKA for severe osteoarthritis of the knee were asked to provide specific information regarding exercised types of sports before surgery and after at least 10 years following TKA. Pre- and postoperative function and pain were evaluated by the use of Tegner-, WOMAC- and VAS Score. After a mean of 14.9 years, a significant improvement regarding pain and function was observed. Pre-operative Tegner- and WOMAC scores revealed significant positive correlations with the post-operative Tegner-Score. Accordingly, a high percentage of patients (70.9%) stayed actively involved in sports. Nevertheless, the number of performing patients has decreased according to the sports impact. 71.3% continued practising low-impact-, 43.7% intermediate-impact sports whereas only 16.4% kept performing high impact sports. We conclude that TKA is highly effective in long-time pain reduction as well as improvement of function. Additionally, we found considerable sports activities preserved in the investigated series. However, sports activities in particular, seem to decrease according to the impact of sports. PMID:27090945

Sports Activity after Low-contact-stress Total Knee Arthroplasty - A long term follow-up study.

PubMed

Vielgut, Ines; Leitner, Lukas; Kastner, Norbert; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

2016-04-19

The purpose of this study was to provide comprehensive long-term data about sports activity levels in patients following total knee arthroplasty (TKA) and to determine the impact of pre-operative function, pain and specific performed sports on the results. 236 patients who have undergone TKA for severe osteoarthritis of the knee were asked to provide specific information regarding exercised types of sports before surgery and after at least 10 years following TKA. Pre- and postoperative function and pain were evaluated by the use of Tegner-, WOMAC- and VAS Score. After a mean of 14.9 years, a significant improvement regarding pain and function was observed. Pre-operative Tegner- and WOMAC scores revealed significant positive correlations with the post-operative Tegner-Score. Accordingly, a high percentage of patients (70.9%) stayed actively involved in sports. Nevertheless, the number of performing patients has decreased according to the sports impact. 71.3% continued practising low-impact-, 43.7% intermediate-impact sports whereas only 16.4% kept performing high impact sports. We conclude that TKA is highly effective in long-time pain reduction as well as improvement of function. Additionally, we found considerable sports activities preserved in the investigated series. However, sports activities in particular, seem to decrease according to the impact of sports.

Hierarchically structured activated carbon for ultracapacitors

NASA Astrophysics Data System (ADS)

Kim, Mok-Hwa; Kim, Kwang-Bum; Park, Sun-Min; Roh, Kwang Chul

2016-02-01

To resolve the pore-associated bottleneck problem observed in the electrode materials used for ultracapacitors, which inhibits the transport of the electrolyte ions, we designed hierarchically structured activated carbon (HAC) by synthesizing a mesoporous silica template/carbon composite and chemically activating it to simultaneously remove the silica template and increase the pore volume. The resulting HAC had a well-designed, unique porous structure, which allowed for large interfaces for efficient electric double-layer formation. Given the unique characteristics of the HAC, we believe that the developed synthesis strategy provides important insights into the design and fabrication of hierarchical carbon nanostructures. The HAC, which had a specific surface area of 1,957 m2 g-1, exhibited an extremely high specific capacitance of 157 F g-1 (95 F cc-1), as well as a high rate capability. This indicated that it had superior energy storage capability and was thus suitable for use in advanced ultracapacitors.

Healthy individuals' immune response to the Bulgarian Crimean-Congo hemorrhagic fever virus vaccine.

PubMed

Mousavi-Jazi, Mehrdad; Karlberg, Helen; Papa, Anna; Christova, Iva; Mirazimi, Ali

2012-09-28

Crimean-Congo hemorrhagic fever virus (CCHFV) poses a great threat to public health due to its high mortality and transmission rate and wide geographical distribution. There is currently no specific antiviral therapy for CCHF. This study provides the first in-depth analysis of the cellular and humoral immune response in healthy individuals following injection of inactivated Bulgarian vaccine, the only CCHFV vaccine available at present. Vaccinated individuals developed robust, anti-CCHFV-specific T-cell activity as measured by IFN-γ ELISpot assay. The frequency of IFN-γ secreting T-cells was 10-fold higher in individuals after vaccination with four doses than after one single dose. High levels of CCHFV antibodies were observed following the first dose, but repeated doses were required to achieve antibodies with neutralizing activity against CCHFV. However, the neutralizing activity in these groups was low. Copyright © 2012 Elsevier Ltd. All rights reserved.

Graphene incorporated, N doped activated carbon as catalytic electrode in redox active electrolyte mediated supercapacitor

NASA Astrophysics Data System (ADS)

Gao, Zhiyong; Liu, Xiao; Chang, Jiuli; Wu, Dapeng; Xu, Fang; Zhang, Lingcui; Du, Weimin; Jiang, Kai

2017-01-01

Graphene incorporated, N doped activated carbons (GNACs) are synthesized by alkali activation of graphene-polypyrrole composite (G-PPy) at different temperatures for application as electrode materials of supercapacitors. Under optimal activation temperature of 700 °C, the resultant samples, labeled as GNAC700, owns hierarchically porous texture with high specific surface area and efficient ions diffusion channels, N, O functionalized surface with apparent pseudocapacitance contribution and high wettability, thus can deliver a moderate capacitance, a high rate capability and a good cycleability when used as supercapacitor electrode. Additionally, the GNAC700 electrode demonstrates high catalytic activity for the redox reaction of pyrocatechol/o-quinone pair in H2SO4 electrolyte, thus enables a high pseudocapacitance from electrolyte. Under optimal pyrocatechol concentration in H2SO4 electrolyte, the electrode capacitance of GNAC700 increases by over 4 folds to 512 F g-1 at 1 A g-1, an excellent cycleability is also achieved simultaneously. Pyridinic- N is deemed to be responsible for the high catalytic activity. This work provides a promising strategy to ameliorate the capacitive performances of supercapacitors via the synergistic interaction between redox-active electrolyte and catalytic electrodes.

Discovery and characterization of a highly efficient enantioselective mandelonitrile hydrolase from Burkholderia cenocepacia J2315 by phylogeny-based enzymatic substrate specificity prediction.

PubMed

Wang, Hualei; Sun, Huihui; Wei, Dongzhi

2013-02-18

A nitrilase-mediated pathway has significant advantages in the production of optically pure (R)-(-)-mandelic acid. However, unwanted byproduct, low enantioselectivity, and specific activity reduce its value in practical applications. An ideal nitrilase that can efficiently hydrolyze mandelonitrile to optically pure (R)-(-)-mandelic acid without the unwanted byproduct is needed. A novel nitrilase (BCJ2315) was discovered from Burkholderia cenocepacia J2315 through phylogeny-based enzymatic substrate specificity prediction (PESSP). This nitrilase is a mandelonitrile hydrolase that could efficiently hydrolyze mandelonitrile to (R)-(-)-mandelic acid, with a high enantiomeric excess of 98.4%. No byproduct was observed in this hydrolysis process. BCJ2315 showed the highest identity of 71% compared with other nitrilases in the amino acid sequence. BCJ2315 possessed the highest activity toward mandelonitrile and took mandelonitrile as the optimal substrate based on the analysis of substrate specificity. The kinetic parameters Vmax, Km, Kcat, and Kcat/Km toward mandelonitrile were 45.4 μmol/min/mg, 0.14 mM, 15.4 s(-1), and 1.1×10(5) M(-1)s(-1), respectively. The recombinant Escherichia coli M15/BCJ2315 had a strong substrate tolerance and could completely hydrolyze mandelonitrile (100 mM) with fewer amounts of wet cells (10 mg/ml) within 1 h. PESSP is an efficient method for discovering an ideal mandelonitrile hydrolase. BCJ2315 has high affinity and catalytic efficiency toward mandelonitrile. This nitrilase has great advantages in the production of optically pure (R)-(-)-mandelic acid because of its high activity and enantioselectivity, strong substrate tolerance, and having no unwanted byproduct. Thus, BCJ2315 has great potential in the practical production of optically pure (R)-(-)-mandelic acid in the industry.

Activated carbon electrode from banana-peel waste for supercapacitor applications

NASA Astrophysics Data System (ADS)

Taer, E.; Taslim, R.; Aini, Z.; Hartati, S. D.; Mustika, W. S.

2017-01-01

Seven types of activated carbon electrode (ACM) have been produced from the banana peel waste for supercapacitor application. The difference type of the electrode was synthesized by the various conditions of carbonization and activation. The production of the ACM was begun by the milling process and molded by a solution casting technique. The next step was followed by drying, carbonization and activation process. Physical properties of the ACM were studied by the N2 gas absorption-desorption method to characterize the specific surface area of the sample. On the other side, the electrochemical properties such as specific capacitance (Csp), specific energy (E) and specific power (P) were resulted by calculating the current (I) and voltage (V) data from the cyclic voltammetry testing. Based on the data obtained the surface area of the ACM has a significant relationship with the electrochemical properties. The specific surface area (SBET), Csp, E and P were found the maximum value as high as 581m2 / g, 68 F/g, 0.75 Wh/kg and 31 W/kg, respectively. Further more, this paper were also analyzed the relationship between electrochemical properties of supercapacitor with the degree of crystallization of the ACM.

Increase of porosity by combining semi-carbonization and KOH activation of formaldehyde resins to prepare high surface area carbons for supercapacitor applications

NASA Astrophysics Data System (ADS)

Heimböckel, Ruben; Kraas, Sebastian; Hoffmann, Frank; Fröba, Michael

2018-01-01

A series of porous carbon samples were prepared by combining a semi-carbonization process of acidic polymerized phenol-formaldehyde resins and a following chemical activation with KOH used in different ratios to increase specific surface area, micropore content and pore sizes of the carbons which is favourable for supercapacitor applications. Samples were characterized by nitrogen physisorption, powder X-ray diffraction, Raman spectroscopy and scanning electron microscopy. The results show that the amount of KOH, combined with the semi-carbonization step had a remarkable effect on the specific surface area (up to SBET: 3595 m2 g-1 and SDFT: 2551 m2 g-1), pore volume (0.60-2.62 cm3 g-1) and pore sizes (up to 3.5 nm). The carbons were tested as electrode materials for electrochemical double layer capacitors (EDLC) in a two electrode setup with tetraethylammonium tetrafluoroborate in acetonitrile as electrolyte. The prepared carbon material with the largest surface area, pore volume and pore sizes exhibits a high specific capacitance of 145.1 F g-1 at a current density of 1 A g-1. With a high specific energy of 31 W h kg-1 at a power density of 33028 W kg-1 and a short time relaxation constant of 0.29 s, the carbon showed high power capability as an EDLC electrode material.

Association of Cell-adhesion Activities with Virulence in Shiga toxin-producing Escherichia coli O103：H2.

PubMed

Kobayashi, Naoki; Maeda, Eriko; Saito, Shioko; Furukawa, Ichiro; Ohnishi, Takahiro; Watanabe, Maiko; Terajima, Jun; Hara-Kudo, Yukiko

2016-01-01

The characteristics of 11 strains of Stx1-producing and Stx2-non-producing STEC O103：H2 were analyzed to investigate the differences in virulence in a single serotype of Shiga toxin (Stx) -producing Escherichia coli (STEC). Differences in the cell-adhesion activity to Caco-2 cells were observed among the strains. The activity of the one strain, isolated from a patient with hemolytic uremic syndrome was 4-20-fold higher than those of the other strains. Although the strains with high cell-adhesion activity showed high expressions of eae, espB, espD, and tir in the locus of enterocyte effacement related with cell-adhesion, those were not specific for this strain. In addition, the Stx1 production level of the strain was not particularly high. It was indicated that the high adhesion activity might be a potential factor to associate serious symptom.

Photoadaptation and protection against active forms of oxygen in the symbiotic procaryote Prochloron sp. and its ascidian host

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

Lesser, M.P.; Stochaj, W.R.

1990-06-01

Superoxide dismutase, ascorbate, peroxidase, and catalase activities were studied in the symbiotic photosynthetic procaryote Prochloron sp. and its ascidian host Lissoclinum patella. The protein-specific activities of these antioxidant enzymes in the Prochloron sp. and L. patella collected at different depths from the Great Barrier Reef, Australia, were directly proportional to irradiance, whereas the pigment concentrations in the Prochloron sp. were inversely proportional to irradiance. The presence of a cyanide-sensitive superoxide dismutase, presumably a Cu-An metalloprotein, in the Prochloron sp. extends the possible phylogenetic distribution of this protein. The concentration of UV-absorbing mycosporine-like amino acids in inversely proportional to irradiance inmore » both the host and symbiont, suggesting that these compounds may not provide sufficient protection against UV radiation in high-irradiance environments. The significant differences in the specific activities of these antioxidant enzymes, cellular photosynthetic pigment concentrations, and UV-absorbing compounds from high- and low-irradiance habitats constitute an adaptive response to different photic environments. These photoadaptive responses are essential to prevent inhibition of photosynthesis by high fluxes of visible and UV radiation.« less

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-09-01

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

Brain-Behavior Mechanisms for the Transfer of Neuromuscular Training Adaptions to Simulated Sport: Initial Findings from the Train the Brain Project.

PubMed

Grooms, Dustin R; Kiefer, Adam W; Riley, Michael A; Ellis, Jonathan D; Thomas, Staci; Kitchen, Katie; DiCesare, Christopher; Bonnette, Scott; Gadd, Brooke; Barber Foss, Kim D; Yuan, Weihong; Silva, Paula; Galloway, Ryan; Diekfuss, Jed; Leach, James; Berz, Kate; Myer, Gregory D

2018-03-27

A limiting factor for reducing anterior cruciate ligament (ACL) injury risk is ensuring that the movement adaptions made during the prevention program transfer to sport-specific activity. Virtual reality provides a mechanism to assess transferability and neuroimaging provides a means to assay the neural processes allowing for such skill transfer. To determine the neural mechanisms for injury risk reducing biomechanics transfer to sport after ACL injury prevention training. Cohort study Setting: Research laboratory Participants: Four healthy high school soccer athletes. Participants completed augmented neuromuscular training utilizing real-time visual feedback. An unloaded knee extension task and a loaded leg-press task was completed with neuroimaging before and after training. A virtual reality soccer specific landing task was also competed following training to assess transfer of movement mechanics. Landing mechanics during the virtual reality soccer task and blood oxygen level dependent signal change during neuroimaging. Increased motor planning, sensory and visual region activity during unloaded knee extension and decreased motor cortex activity during loaded leg-press were highly correlated with improvements in landing mechanics (decreased hip adduction and knee rotation). Changes in brain activity may underlie adaptation and transfer of injury risk reducing movement mechanics to sport activity. Clinicians may be able to target these specific brain processes with adjunctive therapy to facilitate intervention improvements transferring to sport.

Divergence between human and murine peroxisome proliferator-activated receptor alpha ligand specificities[S

PubMed Central

Oswal, Dhawal P.; Balanarasimha, Madhumitha; Loyer, Jeannette K.; Bedi, Shimpi; Soman, Frances L.; Rider, S. Dean; Hostetler, Heather A.

2013-01-01

Peroxisome proliferator-activated receptor α (PPARα) belongs to the family of ligand-dependent nuclear transcription factors that regulate energy metabolism. Although there exists remarkable overlap in the activities of PPARα across species, studies utilizing exogenous PPARα ligands suggest species differences in binding, activation, and physiological effects. While unsaturated long-chain fatty acids (LCFA) and their thioesters (long-chain fatty acyl-CoA; LCFA-CoA) function as ligands for recombinant mouse PPARα (mPPARα), no such studies have been conducted with full-length human PPARα (hPPARα). The objective of the current study was to determine whether LCFA and LCFA-CoA constitute high-affinity endogenous ligands for hPPARα or whether there exist species differences for ligand specificity and affinity. Both hPPARα and mPPARα bound with high affinity to LCFA-CoA; however, differences were noted in LCFA affinities. A fluorescent LCFA analog was bound strongly only by mPPARα, and naturally occurring saturated LCFA was bound more strongly by hPPARα than mPPARα. Similarly, unsaturated LCFA induced transactivation of both hPPARα and mPPARα, whereas saturated LCFA induced transactivation only in hPPARα-expressing cells. These data identified LCFA and LCFA-CoA as endogenous ligands of hPPARα, demonstrated species differences in binding specificity and activity, and may help delineate the role of PPARα as a nutrient sensor in metabolic regulation. PMID:23797899

Fluorescence-based assay as a new screening tool for toxic chemicals

PubMed Central

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-01-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

Fluorescence-based assay as a new screening tool for toxic chemicals.

PubMed

Moczko, Ewa; Mirkes, Evgeny M; Cáceres, César; Gorban, Alexander N; Piletsky, Sergey

2016-09-22

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Fluorescence-based assay as a new screening tool for toxic chemicals

NASA Astrophysics Data System (ADS)

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-09-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

38 CFR 36.4348 - Servicer Appraisal Processing Program.

Code of Federal Regulations, 2012 CFR

2012-07-01

... requirement, routine reviews of SAPP cases will be made by VA staff based upon quality control procedures..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

38 CFR 36.4347 - Lender Appraisal Processing Program.

Code of Federal Regulations, 2012 CFR

2012-07-01

... subsequent office case review requirements, routine reviews of LAPP cases will be made by VA staff based upon..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

38 CFR 36.4348 - Servicer Appraisal Processing Program.

Code of Federal Regulations, 2014 CFR

2014-07-01

... requirement, routine reviews of SAPP cases will be made by VA staff based upon quality control procedures..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

38 CFR 36.4347 - Lender Appraisal Processing Program.

Code of Federal Regulations, 2013 CFR

2013-07-01

... subsequent office case review requirements, routine reviews of LAPP cases will be made by VA staff based upon..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

38 CFR 36.4348 - Servicer Appraisal Processing Program.

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirement, routine reviews of SAPP cases will be made by VA staff based upon quality control procedures..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

38 CFR 36.4347 - Lender Appraisal Processing Program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... subsequent office case review requirements, routine reviews of LAPP cases will be made by VA staff based upon..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

38 CFR 36.4348 - Servicer Appraisal Processing Program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... requirement, routine reviews of SAPP cases will be made by VA staff based upon quality control procedures..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

38 CFR 36.4347 - Lender Appraisal Processing Program.

Code of Federal Regulations, 2014 CFR

2014-07-01

... subsequent office case review requirements, routine reviews of LAPP cases will be made by VA staff based upon..., that its activities do not deviate from high standards of integrity. The quality control system must include frequent, periodic audits that specifically address the appraisal review activity. These audits...

Molecular Characterization of Striated Muscle-Specific Gab1 Isoform as a Critical Signal Transducer for Neuregulin-1/ErbB Signaling in Cardiomyocytes

PubMed Central

Yasui, Taku; Masaki, Takeshi; Arita, Yoh; Ishibashi, Tomohiko; Inagaki, Tadakatsu; Okazawa, Makoto; Oka, Toru; Shioyama, Wataru; Yamauchi-Takihara, Keiko; Komuro, Issei; Sakata, Yasushi; Nakaoka, Yoshikazu

2016-01-01

Grb2-associated binder (Gab) docking proteins regulate signals downstream of a variety of growth factors and receptor tyrosine kinases. Neuregulin-1 (NRG-1), a member of epidermal growth factor family, plays a critical role for cardiomyocyte proliferation and prevention of heart failure via ErbB receptors. We previously reported that Gab1 and Gab2 in the myocardium are essential for maintenance of myocardial function in the postnatal heart via transmission of NRG-1/ErbB-signaling through analysis of Gab1/Gab2 cardiomyocyte-specific double knockout mice. In that study, we also found that there is an unknown high-molecular weight (high-MW) Gab1 isoform (120 kDa) expressed exclusively in the heart, in addition to the ubiquitously expressed low-MW (100 kDa) Gab1. However, the high-MW Gab1 has been molecularly ill-defined to date. Here, we identified the high-MW Gab1 as a striated muscle-specific isoform. The high-MW Gab1 has an extra exon encoding 27 amino acid residues between the already-known 3rd and 4th exons of the ubiquitously expressed low-MW Gab1. Expression analysis by RT-PCR and immunostaining with the antibody specific for the high-MW Gab1 demonstrate that the high-MW Gab1 isoform is exclusively expressed in striated muscle including heart and skeletal muscle. The ratio of high-MW Gab1/ total Gab1 mRNAs increased along with heart development. The high-MW Gab1 isoform in heart underwent tyrosine-phosphorylation exclusively after intravenous administration of NRG-1, among several growth factors. Adenovirus-mediated overexpression of the high-MW Gab1 induces more sustained activation of AKT after stimulation with NRG-1 in cardiomyocytes compared with that of β-galactosidase. On the contrary, siRNA-mediated knockdown of the high-MW Gab1 significantly attenuated AKT activation after stimulation with NRG-1 in cardiomyocytes. Taken together, these findings suggest that the striated muscle-specific high-MW isoform of Gab1 has a crucial role for NRG-1/ErbB signaling in cardiomyocytes. PMID:27861634

Molecular Characterization of Striated Muscle-Specific Gab1 Isoform as a Critical Signal Transducer for Neuregulin-1/ErbB Signaling in Cardiomyocytes.

PubMed

Yasui, Taku; Masaki, Takeshi; Arita, Yoh; Ishibashi, Tomohiko; Inagaki, Tadakatsu; Okazawa, Makoto; Oka, Toru; Shioyama, Wataru; Yamauchi-Takihara, Keiko; Komuro, Issei; Sakata, Yasushi; Nakaoka, Yoshikazu

2016-01-01

Grb2-associated binder (Gab) docking proteins regulate signals downstream of a variety of growth factors and receptor tyrosine kinases. Neuregulin-1 (NRG-1), a member of epidermal growth factor family, plays a critical role for cardiomyocyte proliferation and prevention of heart failure via ErbB receptors. We previously reported that Gab1 and Gab2 in the myocardium are essential for maintenance of myocardial function in the postnatal heart via transmission of NRG-1/ErbB-signaling through analysis of Gab1/Gab2 cardiomyocyte-specific double knockout mice. In that study, we also found that there is an unknown high-molecular weight (high-MW) Gab1 isoform (120 kDa) expressed exclusively in the heart, in addition to the ubiquitously expressed low-MW (100 kDa) Gab1. However, the high-MW Gab1 has been molecularly ill-defined to date. Here, we identified the high-MW Gab1 as a striated muscle-specific isoform. The high-MW Gab1 has an extra exon encoding 27 amino acid residues between the already-known 3rd and 4th exons of the ubiquitously expressed low-MW Gab1. Expression analysis by RT-PCR and immunostaining with the antibody specific for the high-MW Gab1 demonstrate that the high-MW Gab1 isoform is exclusively expressed in striated muscle including heart and skeletal muscle. The ratio of high-MW Gab1/ total Gab1 mRNAs increased along with heart development. The high-MW Gab1 isoform in heart underwent tyrosine-phosphorylation exclusively after intravenous administration of NRG-1, among several growth factors. Adenovirus-mediated overexpression of the high-MW Gab1 induces more sustained activation of AKT after stimulation with NRG-1 in cardiomyocytes compared with that of β-galactosidase. On the contrary, siRNA-mediated knockdown of the high-MW Gab1 significantly attenuated AKT activation after stimulation with NRG-1 in cardiomyocytes. Taken together, these findings suggest that the striated muscle-specific high-MW isoform of Gab1 has a crucial role for NRG-1/ErbB signaling in cardiomyocytes.

Functional and Structural Characterization of Purine Nucleoside Phosphorylase from Kluyveromyces lactis and Its Potential Applications in Reducing Purine Content in Food

PubMed Central

Mahor, Durga; Priyanka, Anu; Prasad, Gandham S; Thakur, Krishan Gopal

2016-01-01

Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway. We report a 1.97 Å resolution crystal structure of homotrimeric KlacPNP with an intrinsically bound hypoxanthine in the active site. KlacPNP belongs to the nucleoside phosphorylase-I (NP-I) family, and it specifically utilizes 6-oxopurine substrates in the following order: inosine > guanosine > xanthosine, but is inactive towards adenosine. To engineer enzymes with broad substrate specificity, we created two point variants, KlacPNPN256D and KlacPNPN256E, by replacing the catalytically active Asn256 with Asp and Glu, respectively, based on structural and comparative sequence analysis. KlacPNPN256D not only displayed broad substrate specificity by utilizing both 6-oxopurines and 6-aminopurines in the order adenosine > inosine > xanthosine > guanosine, but also displayed reversal of substrate specificity. In contrast, KlacPNPN256E was highly specific to inosine and could not utilize other tested substrates. Beer consumption is associated with increased risk of developing gout, owing to its high purine content. Here, we demonstrate that KlacPNP and KlacPNPN256D could be used to catalyze a key reaction involved in lowering beer purine content. Biochemical properties of these enzymes such as activity across a wide pH range, optimum activity at about 25°C, and stability for months at about 8°C, make them suitable candidates for food and beverage industries. Since KlacPNPN256D has broad substrate specificity, a combination of engineered KlacPNP and other enzymes involved in purine degradation could effectively lower the purine content in foods and beverages. PMID:27768715

Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions.

PubMed

Ebner, Matthias; Birschmann, Ingvild; Peter, Andreas; Härtig, Florian; Spencer, Charlotte; Kuhn, Joachim; Blumenstock, Gunnar; Zuern, Christine S; Ziemann, Ulf; Poli, Sven

2017-09-01

In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values. Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070. © 2017 American Heart Association, Inc.

Stringency of substrate specificity of Escherichia coli malate dehydrogenase.

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

Boernke, W. E.; Millard, C. S.; Stevens, P. W.

1995-09-10

Malate dehydrogenase and lactate dehydrogenase are members of the structurally and functionally homologous family of 2-ketoacid dehydrogenases. Both enzymes display high specificity for their respective keto substrates, oxaloacetate and pyruvate. Closer analysis of their specificity, however, reveals that the specificity of malate dehydrogenase is much stricter and less malleable than that of lactate dehydrogenase. Site-specific mutagenesis of the two enzymes in an attempt to reverse their specificity has met with contrary results. Conversion of a specific active-site glutamine to arginine in lactate dehydrogenase from Bacillus stearothermophilus generated an enzyme that displayed activity toward oxaloacetate equal to that of the nativemore » enzyme toward pyruvate (H. M. Wilks et al. (1988) Science 242, 1541-1544). We have constructed a series of mutants in the mobile, active site loop of the Escherichia coli malate dehydrogenase that incorporate the complementary change, conversion of arginine 81 to glutamine, to evaluate the role of charge distribution and conformational flexibility within this loop in defining the substrate specificity of these enzymes. Mutants incorporating the change R81Q all had reversed specificity, displaying much higher activity toward pyruvate than to the natural substrate, oxaloacetate. In contrast to the mutated lactate dehydrogenase, these reversed-specificity mutants were much less active than the native enzyme. Secondary mutations within the loop of the E. coli enzyme (A80N, A80P, A80P/M85E/D86T) had either no or only moderately beneficial effects on the activity of the mutant enzyme toward pyruvate. The mutation A80P, which can be expected to reduce the overall flexibility of the loop, modestly improved activity toward pyruvate. The possible physiological relevance of the stringent specificity of malate dehydrogenase was investigated. In normal strains of E. coli, fermentative metabolism was not affected by expression of the mutant malate dehydrogenase. However, when expressed in a strain of E. coli unable to ferment glucose, the mutant enzyme restored growth and produced lactic acid as the sole fermentation product.« less

In silico simulations of STAT1 and STAT3 inhibitors predict SH2 domain cross-binding specificity.

PubMed

Szelag, Malgorzata; Sikorski, Krzysztof; Czerwoniec, Anna; Szatkowska, Katarzyna; Wesoly, Joanna; Bluyssen, Hans A R

2013-11-15

Signal transducers and activators of transcription (STATs) comprise a family of transcription factors that are structurally related and which participate in signaling pathways activated by cytokines, growth factors and pathogens. Activation of STAT proteins is mediated by the highly conserved Src homology 2 (SH2) domain, which interacts with phosphotyrosine motifs for specific contacts between STATs and receptors and for STAT dimerization. By generating new models for human (h)STAT1, hSTAT2 and hSTAT3 we applied comparative in silico docking to determine SH2-binding specificity of the STAT3 inhibitor stattic, and of fludarabine (STAT1 inhibitor). Thus, we provide evidence that by primarily targeting the highly conserved phosphotyrosine (pY+0) SH2 binding pocket stattic is not a specific hSTAT3 inhibitor, but is equally effective towards hSTAT1 and hSTAT2. This was confirmed in Human Micro-vascular Endothelial Cells (HMECs) in vitro, in which stattic inhibited interferon-α-induced phosphorylation of all three STATs. Likewise, fludarabine inhibits both hSTAT1 and hSTAT3 phosphorylation, but not hSTAT2, by competing with the highly conserved pY+0 and pY-X binding sites, which are less well-preserved in hSTAT2. Moreover we observed that in HMECs in vitro fludarabine inhibits cytokine and lipopolysaccharide-induced phosphorylation of hSTAT1 and hSTAT3 but does not affect hSTAT2. Finally, multiple sequence alignment of STAT-SH2 domain sequences confirmed high conservation between hSTAT1 and hSTAT3, but not hSTAT2, with respect to stattic and fludarabine binding sites. Together our data offer a molecular basis that explains STAT cross-binding specificity of stattic and fludarabine, thereby questioning the present selection strategies of SH2 domain-based competitive small inhibitors. © 2013 Elsevier B.V. All rights reserved.

Bioinspired Nanocomplex for Spatiotemporal Imaging of Sequential mRNA Expression in Differentiating Neural Stem Cells

PubMed Central

2015-01-01

Messenger RNA plays a pivotal role in regulating cellular activities. The expression dynamics of specific mRNA contains substantial information on the intracellular milieu. Unlike the imaging of stationary mRNAs, real-time intracellular imaging of the dynamics of mRNA expression is of great value for investigating mRNA biology and exploring specific cellular cascades. In addition to advanced imaging methods, timely extracellular stimulation is another key factor in regulating the mRNA expression repertoire. The integration of effective stimulation and imaging into a single robust system would significantly improve stimulation efficiency and imaging accuracy, producing fewer unwanted artifacts. In this study, we developed a multifunctional nanocomplex to enable self-activating and spatiotemporal imaging of the dynamics of mRNA sequential expression during the neural stem cell differentiation process. This nanocomplex showed improved enzymatic stability, fast recognition kinetics, and high specificity. With a mechanism regulated by endogenous cell machinery, this nanocomplex realized the successive stimulating motif release and the dynamic imaging of chronological mRNA expression during neural stem cell differentiation without the use of transgenetic manipulation. The dynamic imaging montage of mRNA expression ultimately facilitated genetic heterogeneity analysis. In vivo lateral ventricle injection of this nanocomplex enabled endogenous neural stem cell activation and labeling at their specific differentiation stages. This nanocomplex is highly amenable as an alternative tool to explore the dynamics of intricate mRNA activities in various physiological and pathological conditions. PMID:25494492

Bioinspired nanocomplex for spatiotemporal imaging of sequential mRNA expression in differentiating neural stem cells.

PubMed

Wang, Zhe; Zhang, Ruili; Wang, Zhongliang; Wang, He-Fang; Wang, Yu; Zhao, Jun; Wang, Fu; Li, Weitao; Niu, Gang; Kiesewetter, Dale O; Chen, Xiaoyuan

2014-12-23

Messenger RNA plays a pivotal role in regulating cellular activities. The expression dynamics of specific mRNA contains substantial information on the intracellular milieu. Unlike the imaging of stationary mRNAs, real-time intracellular imaging of the dynamics of mRNA expression is of great value for investigating mRNA biology and exploring specific cellular cascades. In addition to advanced imaging methods, timely extracellular stimulation is another key factor in regulating the mRNA expression repertoire. The integration of effective stimulation and imaging into a single robust system would significantly improve stimulation efficiency and imaging accuracy, producing fewer unwanted artifacts. In this study, we developed a multifunctional nanocomplex to enable self-activating and spatiotemporal imaging of the dynamics of mRNA sequential expression during the neural stem cell differentiation process. This nanocomplex showed improved enzymatic stability, fast recognition kinetics, and high specificity. With a mechanism regulated by endogenous cell machinery, this nanocomplex realized the successive stimulating motif release and the dynamic imaging of chronological mRNA expression during neural stem cell differentiation without the use of transgenetic manipulation. The dynamic imaging montage of mRNA expression ultimately facilitated genetic heterogeneity analysis. In vivo lateral ventricle injection of this nanocomplex enabled endogenous neural stem cell activation and labeling at their specific differentiation stages. This nanocomplex is highly amenable as an alternative tool to explore the dynamics of intricate mRNA activities in various physiological and pathological conditions.

Physical activity patterns of children in Toronto: the relative role of neighbourhood type and socio-economic status.

PubMed

Stone, Michelle R; Faulkner, Guy E; Mitra, Raktim; Buliung, Ron

2012-07-23

A child's opportunity for physical activity and the safety of engaging in activity are influenced by built environment (BE) elements. This study examined the relationship of neighbourhood type and socio-economic status (SES) with activity using a sampling frame that purposely located schools in varying neighbourhoods to ensure that there was variability in BE characteristics and SES. Participants (1,027 Grade 5 & 6 students, Toronto, ON) were drawn from 16 schools that varied by neighbourhood type (pre-1946 "old/urban BE" with grid-based street layout versus post-1946 "new/inner-suburban BE" with looping street layout) and socio-economic status (low and high SES). Physical activity was recorded by accelerometry for seven days. Only children living within 1.6 km of school were included in the analyses (n=713; boys=339, girls=374). Generalized linear mixed models examined sex-specific differences in physical activity across four geographic stratifications: old BE, low-SES (OL); old BE, high-SES (OH); new BE, low-SES (NL); and new BE, high-SES (NH). Children who attended schools in more affluent neighbourhoods (urban and inner-suburban) had more positive physical activity profiles. Across school days, boys were more active in inner-suburban neighbourhoods whereas urban and inner-suburban girls' activity levels were similar. On the weekend, the influence of the neighbourhood environment was stronger, especially for girls and also for boys with respect to total activity and the accumulation of moderate-to-vigorous physical activity. These findings focus attention on the need to consider the broader social and temporal contexts of specific geographic locations when planning and implementing built environment interventions to increase physical activity among children.

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

PubMed

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

2007-08-01

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

Does the high nucleic acid content of individual bacterial cells allow us to discriminate between active cells and inactive cells in aquatic systems?

PubMed

Lebaron, P; Servais, P; Agogué, H; Courties, C; Joux, F

2001-04-01

The nucleic acid contents of individual bacterial cells as determined with three different nucleic acid-specific fluorescent dyes (SYBR I, SYBR II, and SYTO 13) and flow cytometry were compared for different seawater samples. Similar fluorescence patterns were observed, and bacteria with high apparent nucleic acid contents (HNA) could be discriminated from bacteria with low nucleic acid contents (LNA). The best discrimination between HNA and LNA cells was found when cells were stained with SYBR II. Bacteria in different water samples collected from seven freshwater, brackish water, and seawater ecosystems were prelabeled with tritiated leucine and then stained with SYBR II. After labeling and staining, HNA, LNA, and total cells were sorted by flow cytometry, and the specific activity of each cellular category was determined from leucine incorporation rates. The HNA cells were responsible for most of the total bacterial production, and the specific activities of cells in the HNA population varied between samples by a factor of seven. We suggest that nucleic acid content alone can be a better indicator of the fraction of growing cells than total counts and that this approach should be combined with other fluorescent physiological probes to improve detection of the most active cells in aquatic systems.

Does the High Nucleic Acid Content of Individual Bacterial Cells Allow Us To Discriminate between Active Cells and Inactive Cells in Aquatic Systems?

PubMed Central

Lebaron, Philippe; Servais, Pierre; Agogué, Helene; Courties, Claude; Joux, Fabien

2001-01-01

The nucleic acid contents of individual bacterial cells as determined with three different nucleic acid-specific fluorescent dyes (SYBR I, SYBR II, and SYTO 13) and flow cytometry were compared for different seawater samples. Similar fluorescence patterns were observed, and bacteria with high apparent nucleic acid contents (HNA) could be discriminated from bacteria with low nucleic acid contents (LNA). The best discrimination between HNA and LNA cells was found when cells were stained with SYBR II. Bacteria in different water samples collected from seven freshwater, brackish water, and seawater ecosystems were prelabeled with tritiated leucine and then stained with SYBR II. After labeling and staining, HNA, LNA, and total cells were sorted by flow cytometry, and the specific activity of each cellular category was determined from leucine incorporation rates. The HNA cells were responsible for most of the total bacterial production, and the specific activities of cells in the HNA population varied between samples by a factor of seven. We suggest that nucleic acid content alone can be a better indicator of the fraction of growing cells than total counts and that this approach should be combined with other fluorescent physiological probes to improve detection of the most active cells in aquatic systems. PMID:11282632

Redox-active triazatruxene-based conjugated microporous polymers for high-performance supercapacitors† †Electronic supplementary information (ESI) available: Synthetic procedures and characterization data for all new compounds; general experimental method; thermogravimetry curves; PXRD patterns; SEM and TEM images; XPS spectra. See DOI: 10.1039/c6sc05532j Click here for additional data file.

PubMed Central

Li, Xiang-Chun; Zhang, Yizhou; Wang, Chun-Yu; Wan, Yi

2017-01-01

Conjugated polymers (CPs) have been intensively explored for various optoelectronic applications in the last few decades. Nevertheless, CP based electrochemical energy storage devices such as supercapacitors remain largely unexplored. This is mainly owing to the low specific capacitance, poor structural/electrochemical stability, and low energy density of most existing CPs. In this contribution, a novel set of redox-active conjugated microporous polymers, TAT-CMP-1 and TAT-CMP-2, based on nitrogen-rich and highly conductive triazatruxene building blocks, were successfully designed and synthesized to explore their potential application as efficient and stable electrode materials for supercapacitors. Despite a moderate surface area of 88 m2 g–1 for TAT-CMP-1 and 106 m2 g–1 for TAT-CMP-2, exceptional specific capacitances of 141 F g–1 and 183 F g–1 were achieved at a current density of 1 A g–1. The resulting polymers exhibited unusually high areal specific capacitance (>160 μF cm–2), which is attributed to the pseudocapacitance resulting from redox-active structures with high nitrogen content. More importantly, the TAT-CMP-2 electrode exhibits excellent cycling stability: only 5% capacitance fading is observed after 10 000 cycles at a high current density of 10 A g–1, enabling the possible use of these materials as electrodes in electrochemical devices. PMID:28451362

High-Performance Overall Water Splitting Electrocatalysts Derived from Cobalt-Based Metal–Organic Frameworks

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

You, Bo; Jiang, Nan; Sheng, Meili

2015-11-05

The design of active, robust, and nonprecious electrocatalysts with both H 2 and O 2 evolution reaction (HER and OER) activities for overall water splitting is highly desirable but remains a grand challenge. Here in this article, we report a facile two-step method to synthesize porous Co-P/NC nanopolyhedrons composed of CoP x (a mixture of CoP and Co 2P) nanoparticles embedded in N-doped carbon matrices as electrocatalysts for overall water splitting. The Co-P/NC catalysts were prepared by direct carbonization of Co-based zeolitic imidazolate framework (ZIF-67) followed by phosphidation. Benefiting from the large specific surface area, controllable pore texture, and highmore » nitrogen content of ZIF (a subclass of metal–organic frameworks), the optimal Co-P/NC showed high specific surface area of 183 m 2 g -1 and large mesopores, and exhibited remarkable catalytic performance for both HER and OER in 1.0 M KOH, affording a current density of 10 mA cm -2 at low overpotentials of -154 mV for HER and 319 mV for OER, respectively. Furthermore, a Co-P/NC-based alkaline electrolyzer approached 165 mA cm -2 at 2.0 V, superior to that of Pt/IrO 2 couple, along with strong stability. Various characterization techniques including X-ray absorption spectroscopy (XAS) revealed that the superior activity and strong stability of Co-P/NC originated from its 3D interconnected mesoporosity with high specific surface area, high conductivity, and synergistic effect of CoP x encapsulated within N-doped carbon matrices.« less

Aeronautics research and technology program and specific objectives

NASA Technical Reports Server (NTRS)

1981-01-01

Aeronautics research and technology program objectives in fluid and thermal physics, materials and structures, controls and guidance, human factors, multidisciplinary activities, computer science and applications, propulsion, rotorcraft, high speed aircraft, subsonic aircraft, and rotorcraft and high speed aircraft systems technology are addressed.

Time course of brain activation elicited by basic emotions.

PubMed

Hot, Pascal; Sequeira, Henrique

2013-11-13

Whereas facial emotion recognition protocols have shown that each discrete emotion has a specific time course of brain activation, there is no electrophysiological evidence to support these findings for emotional induction by complex pictures. Our objective was to specify the differences between the time courses of brain activation elicited by feelings of happiness and, with unpleasant pictures, by feelings of disgust and sadness. We compared event-related potentials (ERPs) elicited by the watching of high-arousing pictures from the International Affective Picture System, selected to induce specific emotions. In addition to a classical arousal effect on late positive components, we found specific ERP patterns for each emotion in early temporal windows (<200 ms). Disgust was the first emotion to be associated with different brain processing after 140 ms, whereas happiness and sadness differed in ERPs elicited at the frontal and central sites after 160 ms. Our findings highlight the limits of the classical averaging of ERPs elicited by different emotions inside the same valence and suggest that each emotion could elicit a specific temporal pattern of brain activation, similar to those observed with emotional face recognition.

Protective effect of extract of Crataegus pinnatifida pollen on DNA damage response to oxidative stress.

PubMed

Cheng, Ni; Wang, Yuan; Gao, Hui; Yuan, Jialing; Feng, Fan; Cao, Wei; Zheng, Jianbin

2013-09-01

The protective effect of extract of Crataegus pinnatifida (Rosaceae) pollen (ECPP) on the DNA damage response to oxidative stress was investigated and assessed with an alkaline single-cell gel electrophoresis (SCGE) assay and pBR322 plasmid DNA breaks in site-specific and non-site-specific systems. Total phenolic content, total flavonoid content, individual phenolic compounds, antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH), radical scavenging activity, FRAP, and chelating activity) were also determined. The results showed that ECPP possessed a strong ability to protect DNA from being damaged by hydroxyl radicals in both the site-specific system and the non-site-specific system. It also exhibited a cytoprotection effect in mouse lymphocytes against H₂O₂-induced DNA damage. These protective effects may be related to its high total phenolic content (17.65±0.97 mg GAE/g), total flavonoid content (8.04±0.97 mg rutin/g), strong free radical scavenging activity and considerable ferrous ion chelating ability (14.48±0.21 mg Na₂EDTA/g). Copyright © 2013 Elsevier Ltd. All rights reserved.

High resolution monitoring system for IRE stack releases.

PubMed

Deconninck, B; De Lellis, C

2013-11-01

The main activity of IRE (Institute for Radio-Element) is radioisotope production of bulk (99)Mo and (131)I for medical application (diagnosis and therapy). Those isotopes are chemically extracted from HEU (High Enriched Uranium) targets activated in reactors. During this process, fission products are released from the targets, including noble gases isotopes (Xe and Kr). Like any nuclear plant, IRE has release limits which are given by the Belgium authority and moreover IRE is in the process of continuously reducing the level of its releases. To achieve this mission, the need of an accurate tool is necessary and IRE has developed a specific monitoring system using a high resolution detector in order to identify and accurately estimate its gaseous releases. This system has a continuous air sampling system in the plant main stack. The sampled gases cross charcoal cartridges where they are slowed down and concentrated for higher detection efficiency. In front of those cartridges is installed an HPGe detector with a detection chain connected to a specific analysis system allowing on-line spectrum analysis. Each isotope can be separately followed without interferences, especially during the production process where high activity can be released. Due to its conception, the system also allows to measure iodine isotopes by integration on the charcoal cartridges. This device is of great help for accurately estimate IRE releases and to help for understanding specific releases and their origin in the production or maintenance process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of Activity-Based Probes to Develop High Throughput Screening Assays That Can Be Performed in Complex Cell Extracts

PubMed Central

Deu, Edgar; Yang, Zhimou; Wang, Flora; Klemba, Michael; Bogyo, Matthew

2010-01-01

Background High throughput screening (HTS) is one of the primary tools used to identify novel enzyme inhibitors. However, its applicability is generally restricted to targets that can either be expressed recombinantly or purified in large quantities. Methodology and Principal Findings Here, we described a method to use activity-based probes (ABPs) to identify substrates that are sufficiently selective to allow HTS in complex biological samples. Because ABPs label their target enzymes through the formation of a permanent covalent bond, we can correlate labeling of target enzymes in a complex mixture with inhibition of turnover of a substrate in that same mixture. Thus, substrate specificity can be determined and substrates with sufficiently high selectivity for HTS can be identified. In this study, we demonstrate this method by using an ABP for dipeptidyl aminopeptidases to identify (Pro-Arg)2-Rhodamine as a specific substrate for DPAP1 in Plasmodium falciparum lysates and Cathepsin C in rat liver extracts. We then used this substrate to develop highly sensitive HTS assays (Z’>0.8) that are suitable for use in screening large collections of small molecules (i.e >300,000) for inhibitors of these proteases. Finally, we demonstrate that it is possible to use broad-spectrum ABPs to identify target-specific substrates. Conclusions We believe that this approach will have value for many enzymatic systems where access to large amounts of active enzyme is problematic. PMID:20700487

Making ultrafine and highly-dispersive multimetallic nanoparticles in three-dimensional graphene with supercritical fluid as excellent electrocatalyst for oxygen reduction reaction

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

Zhou, Yazhou; Yen, Clive H.; Hu, Yun Hang

2016-01-01

Three-dimensional (3D) graphene showed an advanced support for designing porous electrode materials due to its high specific surface area, large pore volume, and excellent electronic property. However, the electrochemical properties of reported porous electrode materials still need to be improved further. The current challenge is how to deposit desirable nanoparticles (NPs) with controllable structure, loading and composition in 3D graphene while maintaining the high dispersion. Herein, we demonstrate a modified supercritical fluid (SCF) technique to address this issue by controlling the SCF system. Using this superior method, a series of Pt-based/3D graphene materials with the ultrafine-sized, highly dispersive and controllablemore » composition multimetallic NPs were successfully synthesized. Specifically, the resultant Pt40Fe60/3D graphene showed a significant enhancement in electrocatalytic performance for the oxygen reduction reaction (ORR), including a factor of 14.2 enhancement in mass activity (1.70 A mgPt 1), a factor of 11.9 enhancement in specific activity (1.55 mA cm 2), and higher durability compared with that of Pt/C catalyst. After careful comparison, the Pt40Fe60/3D graphene catalyst shows the higher ORR activity than most of the reported similar 3D graphene-based catalysts. The successful synthesis of such attractive materials by this method also paves the way to develop 3D graphene in widespread applications.« less

Nanostructure and force spectroscopy analysis of human peripheral blood CD4+ T cells using atomic force microscopy.

PubMed

Hu, Mingqian; Wang, Jiongkun; Cai, Jiye; Wu, Yangzhe; Wang, Xiaoping

2008-09-12

To date, nanoscale imaging of the morphological changes and adhesion force of CD4(+) T cells during in vitro activation remains largely unreported. In this study, we used atomic force microscopy (AFM) to study the morphological changes and specific binding forces in resting and activated human peripheral blood CD4(+) T cells. The AFM images revealed that the volume of activated CD4(+) T cells increased and the ultrastructure of these cells also became complex. Using a functionalized AFM tip, the strength of the specific binding force of the CD4 antigen-antibody interaction was found to be approximately three times that of the unspecific force. The adhesion forces were not randomly distributed over the surface of a single activated CD4(+) T cell, indicated that the CD4 molecules concentrated into nanodomains. The magnitude of the adhesion force of the CD4 antigen-antibody interaction did not change markedly with the activation time. Multiple bonds involved in the CD4 antigen-antibody interaction were measured at different activation times. These results suggest that the adhesion force involved in the CD4 antigen-antibody interaction is highly selective and of high affinity.

Video in English for Specific Purposes.

ERIC Educational Resources Information Center

Hristova, Rozinka

For an English for Specific Purposes (ESP) course to be efficient, the learner and his/her communicative needs should be central in deciding course content and activities. Video can be highly motivating by presenting live instances of communication in the target environment. It is a valuable medium for intensive analysis of visual and nonverbal…

Specification of High Activity Gamma-Ray Sources.

ERIC Educational Resources Information Center

International Commission on Radiation Units and Measurements, Washington, DC.

The report is concerned with making recommendations for the specifications of gamma ray sources, which relate to the quantity of radioactive material and the radiation emitted. Primary consideration is given to sources in teletherapy and to a lesser extent those used in industrial radiography and in irradiation units used in industry and research.…

Instrument for evaluation of sedentary lifestyle in patients with high blood pressure.

PubMed

Lopes, Marcos Venícios de Oliveira; da Silva, Viviane Martins; de Araujo, Thelma Leite; Guedes, Nirla Gomes; Martins, Larissa Castelo Guedes; Teixeira, Iane Ximenes

2015-01-01

this article describes the diagnostic accuracy of the International Physical Activity Questionnaire to identify the nursing diagnosis of sedentary lifestyle. a diagnostic accuracy study was developed with 240 individuals with established high blood pressure. The analysis of diagnostic accuracy was based on measures of sensitivity, specificity, predictive values, likelihood ratios, efficiency, diagnostic odds ratio, Youden index, and area under the receiver-operating characteristic curve. statistical differences between genders were observed for activities of moderate intensity and for total physical activity. Age was negatively correlated with activities of moderate intensity and total physical activity. the analysis of area under the receiver-operating characteristic curve for moderate intensity activities, walking, and total physical activity showed that the International Physical Activity Questionnaire present moderate capacity to correctly classify individuals with and without sedentary lifestyle.

Ternary carbon composite films for supercapacitor applications

NASA Astrophysics Data System (ADS)

Tran, Minh-Hai; Jeong, Hae Kyung

2017-09-01

A simple, binder-free, method of making supercapacitor electrodes is introduced, based on modification of activated carbon with graphite oxide and carbon nanotubes. The three carbon precursors of different morphologies support each other to provide outstanding electrochemical performance, such as high capacitance and high energy density. The ternary carbon composite shows six times higher specific capacitance compared to that of activated carbon itself with high retention. The excellent electrochemical properties of the ternary composite attribute to the high surface area of 1933 m2 g-1 and low equivalent series resistance of 2 Ω, demonstrating that it improve the electrochemical performance for supercapacitor applications.

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

PubMed

Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

2008-09-01

Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

Normative legal regulating of vehicles with a high degree of automation of control: strategy and tactics for implementation in Russia

NASA Astrophysics Data System (ADS)

Kisulenko, B. V.; Bocharov, A. V.; Pugachev, V. V.

2018-02-01

The article discusses the risks specific to vehicles with a high level of automation of control, and conditions the limits on the operating conditions of such vehicles. The article determines existing legal barriers to the implementation of autonomous vehicles. The article contains an analysis of foreign practice of regulating in the European Union, Japan and the United States and information about the UNECE activities aimed at enabling operation of vehicles with a high degree of automation control. Basing on the results of the analysis, the authors made proposals for removal of legal barriers. The article also contains proposals for the development of specific requirements for autonomous vehicles associated with their specific features of design.

Cortical theta wanes for language.

PubMed

Hermes, Dora; Miller, Kai J; Vansteensel, Mariska J; Edwards, Erik; Ferrier, Cyrille H; Bleichner, Martin G; van Rijen, Peter C; Aarnoutse, Erik J; Ramsey, Nick F

2014-01-15

The role of low frequency oscillations in language areas is not yet understood. Using ECoG in six human subjects, we studied whether different language regions show prominent power changes in a specific rhythm, in similar manner as the alpha rhythm shows the most prominent power changes in visual areas. Broca's area and temporal language areas were localized in individual subjects using fMRI. In these areas, the theta rhythm showed the most pronounced power changes and theta power decreased significantly during verb generation. To better understand the role of this language-related theta decrease, we then studied the interaction between low frequencies and local neuronal activity reflected in high frequencies. Amplitude-amplitude correlations showed that theta power correlated negatively with high frequency activity, specifically across verb generation trials. Phase-amplitude coupling showed that during control trials, high frequency power was coupled to theta phase, but this coupling decreased significantly during verb generation trials. These results suggest a dynamic interaction between the neuronal mechanisms underlying the theta rhythm and local neuronal activity in language areas. As visual areas show a pronounced alpha rhythm that may reflect pulsed inhibition, language regions show a pronounced theta rhythm with highly similar features. © 2013.

Task-specific reorganization of the auditory cortex in deaf humans

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-24

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

Differential skeletal muscle proteome of high- and low-active mice

PubMed Central

Dangott, Lawrence J.; Schmitt, Emily E.; Vellers, Heather L.; Lightfoot, J. Timothy

2014-01-01

Physical inactivity contributes to cardiovascular disease, type II diabetes, obesity, and some types of cancer. While the literature is clear that there is genetic regulation of physical activity with existing gene knockout data suggesting that skeletal muscle mechanisms contribute to the regulation of activity, actual differences in end-protein expression between high- and low-active mice have not been investigated. This study used two-dimensional differential gel electrophoresis coupled with mass spectrometry to evaluate the proteomic differences between high-active (C57L/J) and low-active (C3H/HeJ) mice in the soleus and extensor digitorum longus (EDL). Furthermore, vivo-morpholinos were used to transiently knockdown candidate proteins to confirm their involvement in physical activity regulation. Proteins with higher expression patterns generally fell into the calcium-regulating and Krebs (TCA) cycle pathways in the high-active mice (e.g., annexin A6, P = 0.0031; calsequestrin 1; P = 0.000025), while the overexpressed proteins in the low-active mice generally fell into cytoskeletal structure- and electron transport chain-related pathways (e.g., ATPase, P = 0.031; NADH dehydrogenase, P = 0.027). Transient knockdown of annexin A6 and calsequestrin 1 protein of high-active mice with vivo-morpholinos resulted in decreased physical activity levels (P = 0.001). These data suggest that high- and low-active mice have unique protein expression patterns and that each pattern contributes to the peripheral capability to be either high- or low-active, suggesting that different specific mechanisms regulate activity leading to the high- or low-activity status of the animal. PMID:24505100

Ameliorative effect of vitamin E on hepatic oxidative stress and hypoimmunity induced by high-fat diet in turbot (Scophthalmus maximus).

PubMed

Jia, Yudong; Jing, Qiqi; Niu, Huaxin; Huang, Bin

2017-08-01

This study was conducted to examine the effects of vitamin E on growth performance, oxidative stress and non-specific immunity of turbot (Scophthalmus maximus) fed with high-fat diet. Results showed that high-fat diet significantly increased hepatosomatic index, viscerosomatic index, hepatic malondialdehyde level and decreased catalase and superoxide dismutase activities, whereas final weight, specific growth rate and survival rate remained unchanged. Meanwhile, nitro blue tetrazolium positive leucocytes of head kidney, respiratory burst activity in head-kidney macrophage, phagocytic index and serum lysozyme activity were significantly reduced after feeding with high-fat diet. Furthermore, fish fed with high-fat diet promoted higher expression of heat shock protein (hsp70, hsp90), and inhibited expression of complement component 3 (c3) in the liver and tumor necrosis factor-α (tnf-α), interleukine 1β (il-1β), toll like receptor 22 (tlr-22) in the spleen and head-kidney, respectively. However, simultaneous supplementation with 480 mg kg -1 vitamin E protected turbot against high-fat diet-induced hepatic oxidative stress, hypoimmunity through attenuating lipid peroxidation, renewing antioxidant enzymes activities and nonspecific immune responses, and modulating the expression of stress protein (hsp70, hsp90) and immune-related genes (c3, tnf-α, il-1β, tlr-22). In conclusion, the obtained results indicate the vitamin E as a wildly used functional feed additive contributes potentially to alleviate high-fat diet-induced hepatic oxidative stress and hypoimmunity, maintain the health, and improve the broodstock management for turbot. Copyright © 2017 Elsevier Ltd. All rights reserved.

Highly specific preoperative selection of solitary parathyroid adenoma cases in primary hyperparathyroidism by quantitative image analysis of the early-phase Technetium-99m sestamibi scan.

PubMed

Kim, DaeHee; Rhodes, Jeffrey A; Hashim, Jeffrey A; Rickabaugh, Lawrence; Brams, David M; Pinkus, Edward; Dou, Yamin

2018-06-07

Highly specific preoperative localizing test is required to select patients for minimally invasive parathyroidectomy (MIP) in lieu of traditional four-gland exploration. We hypothesized that Tc-99m sestamibi scan interpretation incorporating numerical measurements on the degree of asymmetrical activity from bilateral thyroid beds can be useful in localizing single adenoma for MIP. We devised a quantitative interpretation method for Tc-99m sestamibi scan based on the numerically graded asymmetrical activity on early phase. The numerical ratio value of each scan was obtained by dividing the number of counts from symmetrically drawn regions of interest (ROI) over bilateral thyroid beds. The final pathology and clinical outcome of 109 patients were used to perform receiver operating curve (ROC) analysis. Receiver operating curve analysis revealed the area under the curve (AUC) was calculated to be 0.71 (P = 0.0032), validating this method as a diagnostic tool. The optimal cut-off point for the ratio value with maximal combined sensitivity and specificity was found with corresponding sensitivity of 67.9% (56.5-77.2%, 95% CI) and specificity of 75.0% (52.8-91.8%, 95% CI). An additional higher cut-off with higher specificity with minimal possible sacrifice on sensitivity was also selected, yielding sensitivity of 28.6% (18.8-38.6%, 95% CI) and specificity of 90.0% (69.6-98.8%, 95% CI). Our results demonstrated that the more asymmetrical activity on the initial phase, the more successful it is to localize a single parathyroid adenoma on sestamibi scans. Using early-phase Tc-99m sestamibi scan only, we were able to select patients for minimally invasive parathyroidectomy with 90% specificity. © 2018 The Royal Australian and New Zealand College of Radiologists.

Photoelectrocyclization as an activation mechanism for organelle-specific live-cell imaging probes.

PubMed

Tran, Mai N; Chenoweth, David M

2015-05-26

Photoactivatable fluorophores are useful tools in live-cell imaging owing to their potential for precise spatial and temporal control. In this report, a new photoactivatable organelle-specific live-cell imaging probe based on a 6π electrocyclization/oxidation mechanism is described. It is shown that this new probe is water-soluble, non-cytotoxic, cell-permeable, and useful for mitochondrial imaging. The probe displays large Stokes shifts in both pre-activated and activated forms, allowing simultaneous use with common dyes and fluorescent proteins. Sequential single-cell activation experiments in dense cellular environments demonstrate high spatial precision and utility in single- or multi-cell labeling experiments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine.

PubMed

Di Giorgio, Carole; Shimi, Kamal; Boyer, Gérard; Delmas, Florence; Galy, Jean-Pierre

2007-10-01

Two new series of diaminoacridinic derivatives obtained from proflavine and N-(6-amino-3-acridinyl)acetamide were synthesised and assessed for their cytotoxic and antileishmanial activities. Two compounds, N-[6-(acetylamino)-3-acridinyl]acetamide and N-[6-(benzoylamino)-3-acridinyl]benzamide demonstrated highly specific antileishmanial properties against the intracellular amastigote form of the parasite. Structure-activity relationships established that the antiproliferative activity against human cells was greatly enhanced by the presence of a benzoylamino group in 6-mono-substituted acridines, while the presence of two acetylamino or benzoylamino groups in 3,6-di-substituted acridines strongly increased the specificity of the molecules for Leishmania parasite, suggesting that symmetric conformations could preferentially interfere with Leishmania metabolism.

Local entrainment of oscillatory activity induced by direct brain stimulation in humans

PubMed Central

Amengual, Julià L.; Vernet, Marine; Adam, Claude; Valero-Cabré, Antoni

2017-01-01

In a quest for direct evidence of oscillation entrainment, we analyzed intracerebral electroencephalographic recordings obtained during intracranial electrical stimulation in a cohort of three medication-resistant epilepsy patients tested pre-surgically. Spectral analyses of non-epileptogenic cerebral sites stimulated directly with high frequency electrical bursts yielded episodic local enhancements of frequency-specific rhythmic activity, phase-locked to each individual pulse. These outcomes reveal an entrainment of physiological oscillatory activity within a frequency band dictated by the rhythm of the stimulation source. Our results support future uses of rhythmic stimulation to elucidate the causal contributions of synchrony to specific aspects of human cognition and to further develop the therapeutic manipulation of dysfunctional rhythmic activity subtending the symptoms of some neuropsychiatric conditions. PMID:28256510

High-frequency stimulation of the temporoammonic pathway induces input-specific long-term potentiation in subicular bursting cells.

PubMed

Fidzinski, Pawel; Wawra, Matthias; Bartsch, Julia; Heinemann, Uwe; Behr, Joachim

2012-01-09

The subiculum (Sub) as a part of the hippocampal formation is thought to play a functional role in learning and memory. In addition to its major input from CA1 pyramidal cells, the subiculum receives input from the entorhinal cortex (EC) via the temporoammonic pathway. Thus far, synaptic plasticity in the subiculum was mainly investigated at CA1-Sub synapses. According to their spiking pattern, pyramidal cells in the subiculum were classified as bursting cells and non-bursting cells. In the present study, we demonstrate that subicular bursting cells show input-specific forms of long-term potentiation (LTP). At CA1-Sub synapses, bursting cells have been shown to express a presynaptic NMDA receptor-dependent LTP that depends on the activation of a cAMP-PKA cascade (Wozny et al., Journal of Physiology 2008). In contrast, at EC-Sub synapses the induction of LTP in bursting cells shows a high induction-threshold and relies on the activation of postsynaptic NMDA receptors, postsynaptic depolarization and postsynaptic Ca(2+) influx. Each form of LTP is input-specific and fails to induce heterosynaptic plasticity. Taken together, our data suggest that distinct, input-specific mechanisms govern high frequency-induced LTP at subicular bursting cells' synapses. Copyright © 2011 Elsevier B.V. All rights reserved.

Transcriptome analysis of Pseudomonas syringae identifies new genes, ncRNAs, and antisense activity

USDA-ARS?s Scientific Manuscript database

To fully understand how bacteria respond to their environment, it is essential to assess genome-wide transcriptional activity. New high throughput sequencing technologies make it possible to query the transcriptome of an organism in an efficient unbiased manner. We applied a strand-specific method t...

An Experiential Learning Activity Demonstrating Normal and Phobic Anxiety

ERIC Educational Resources Information Center

Canu, Will H.

2008-01-01

This article describes an activity for an undergraduate abnormal psychology course that used student-generated data to illustrate normal versus clinically significant anxiety responses related to specific phobias. Students (N = 37) viewed 14 images of low- or high-anxiety valence and rated their subjective response to each. Discussion in a…

Design, fabrication, and evaluation of on-chip micro-supercapacitors

NASA Astrophysics Data System (ADS)

Beidaghi, Majid

Due to the increasing demand for high power and reliable miniaturized energy storage devices, the development of micro-supercapacitors or electrochemical micro-capacitors have attracted much attention in recent years. This dissertation investigates several strategies to develop on-chip micro-supercapacitors with high power and energy density. Micro-supercapacitors based on interdigitated carbon micro-electrode arrays are fabricated through carbon microelectromechanical systems (C-MEMS) technique which is based on carbonization of patterned photoresist. To improve the capacitive behavior, electrochemical activation is performed on carbon micro-electrode arrays. The developed micro-supercapacitors show specific capacitances as high as 75 mFcm-2 at a scan rate of 5 mVs -1 after electrochemical activation for 30 minutes. The capacitance loss is less than 13% after 1000 cyclic voltammetry (CV) cycles. These results indicate that electrochemically activated C-MEMS micro-electrode arrays are promising candidates for on-chip electrochemical micro-capacitor applications. The energy density of micro-supercapacitors was further improved by conformal coating of polypyrrole (PPy) on C-MEMS structures. In these types of micro-devices the three dimensional (3D) carbon microstructures serve as current collectors for high energy density PPy electrodes. The electrochemical characterizations of these micro-supercapacitors show that they can deliver a specific capacitance of about 162.07 mFcm-2 and a specific power of 1.62mWcm -2 at a 20 mVs-1 scan rate. Addressing the need for high power micro-supercapacitors, the application of graphene as electrode materials for micro-supercapacitor was also investigated. The present study suggests a novel method to fabricate graphene-based micro-supercapacitors with thin film or in-plane interdigital electrodes. The fabricated micro-supercapacitors show exceptional frequency response and power handling performance and could effectively charge and discharge at rates as high as 50 Vs-1. CV measurements show that the specific capacitance of the micro-supercapacitor based on reduced graphene oxide and carbon nanotube composites is 6.1 mFcm -2 at scan rate of 0.01Vs-1. At a very high scan rate of 50 Vs-1, a specific capacitance of 2.8 mFcm-2 (stack capacitance of 3.1 Fcm-3) is recorded. This unprecedented performance can potentially broaden the future applications of micro-supercapacitors.

Indole-3-acetic acid biosynthetic pathway and aromatic amino acid aminotransferase activities in Pantoea dispersa strain GPK.

PubMed

Kulkarni, G B; Nayak, A S; Sajjan, S S; Oblesha, A; Karegoudar, T B

2013-05-01

This investigation deals with the production of IAA by a bacterial isolate Pantoea dispersa strain GPK (PDG) identified by 16S rRNA gene sequence analysis. HPLC and Mass spectral analysis of metabolites from bacterial spent medium revealed that, IAA production by PDG is Trp-dependent and follows indole-3-pyruvic acid (IPyA) pathway. Substrate specificity study of aromatic amino acid aminotransferase (AAT) showed high activities, only when tryptophan (Trp) and α-ketoglutarate (α-kg) were used as substrates. AAT is highly specific for Trp and α-kg as amino group donor and acceptor, respectively. The effect of exogenous IAA on bacterial growth was established. Low concentration of exogenous IAA induced the growth, whereas high concentration decreased the growth of bacterium. PDG treatment significantly increased the root length, shoot length and dry mass of the chickpea and pigeon pea plants. © 2013 The Society for Applied Microbiology.

Specificity and mechanism of protein kinase C activation by sn-1,2-diacylglycerols.

PubMed Central

Ganong, B R; Loomis, C R; Hannun, Y A; Bell, R M

1986-01-01

The specificity of protein kinase C activation by sn-1,2-diacylglycerols and analogues was investigated by using a Triton X-100 mixed micellar assay [Hannun, Y. A., Loomis, C. R. & Bell, R. M. (1985) J. Biol. Chem. 260, 10039-10043]. Analogues containing acyl or alkyl chains eight carbons in length were synthesized because sn-1,2-dioctanoylglycerol is an effective cell-permeant activator of protein kinase C. These analogues were tested as activators and antagonists of rat brain protein kinase C to determine the exact structural features important for activity. The analogues established that activation of protein kinase C by diacylglycerols is highly specific. Several analogues established that both carbonyl moieties of the oxygen esters are required for maximal activity and that the 3-hydroxyl moiety is also required. None of the analogues were antagonists. These data, combined with previous investigations, permitted formulation of a model of protein kinase C activation. A three-point attachment of sn-1,2-diacylglycerol to the surface-bound protein kinase C-phosphatidylserine-Ca2+ complex is envisioned to cause activation. Direct ligation of diacylglycerol to Ca2+ is proposed to be an essential step in the mechanism of activation of protein kinase C. Images PMID:3456578

Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis

PubMed Central

Brust, Belinda; Lecoufle, Mélanie; Tuaillon, Edouard; Dedieu, Luc; Canaan, Stéphane; Valverde, Viviane; Kremer, Laurent

2011-01-01

Background New diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB. Methods Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. Results A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. Conclusion These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB. PMID:21966416

Isolation and characterization of two novel root-specific promoters in rice (Oryza sativa L.).

PubMed

Li, Yuanya; Liu, Shaojun; Yu, Zhiming; Liu, Yu; Wu, Ping

2013-06-01

Novel root-specific promoters are important for developing methods to drive root-specific gene expression for nutrient and water absorption. RT-PCR (reverse transcription polymerase chain reaction) analysis identified high expression levels of Os03g01700 and Os02g37190 in root tissues across developmental stages in comparison with the constitutive genes OsAct1 (rice Actin1 gene), OsUbi1 (rice polyubiquitin rubi1 gene), and OsCc1 (rice cytochrome c gene). The copy numbers of Os03g01700 and Os02g37190 were evaluated by qRT-PCR. The results showed that Os03g01700 and Os02g37190 transcripts were highly accumulated in the examined root tissues but were not detected in young embryos or leaves at the indicated days after germination or in the panicle, in contrast to the ubiquitous expression of OsAct1, OsUbi1, and OsCc1. Additionally, the promoter regions of these two genes were linked to the GUSplus reporter gene and transformed into rice. GUS staining of the transgenic plants showed that the Os03g01700 and Os02g37190 promoters were active in primary and secondary roots throughout the developmental stages, except in root hairs. The GUSPlus transcript levels were also highly root-specific in the transgenic rice. Overall, the two promoters are highly active in the root tissues of rice and can be useful for the root-specific enhancement of target gene(s). Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An interferometer for high-resolution optical surveillance from geostationary orbit

NASA Astrophysics Data System (ADS)

Bonino, L.; Bresciani, F.; Piasini, G.; Flebus, C.; Lecat, J.-H.; Roose, S.; Pisani, M.; Cabral, A.; Rebordão, J.; Proença, C.; Costal, J.; Lima, P. U.; Loix, N.; Musso, F.

2017-11-01

The activities described in this paper have been developed in the frame of the EUCLID CEPA 9 RTP 9.9 "High Resolution Optical Satellite Sensor" project of the WEAO Research Cell. They have been focused on the definition of an interferometric instrument optimised for the high-resolution optical surveillance from geostationary orbit (GEO) by means of the synthetic aperture technique, and on the definition and development of the related enabling technologies. In this paper we describe the industrial team, the selected mission specifications and overview of the whole design and manufacturing activities performed.

Nitrogen-doped hierarchical lamellar porous carbon synthesized from the fish scale as support material for platinum nanoparticle electrocatalyst toward the oxygen reduction reaction.

PubMed

Liu, Haijing; Cao, Yinliang; Wang, Feng; Huang, Yaqin

2014-01-22

Novel hierarchical lamellar porous carbon (HLPC) with high BET specific surface area of 2730 m(2) g(-1) and doped by nitrogen atoms has been synthesized from the fish scale without any post-synthesis treatment, and applied to support the platinum (Pt) nanoparticle (NP) catalysts (Pt/HLPC). The Pt NPs could be highly dispersed on the porous surface of HLPC with a narrow size distribution centered at ca. 2.0 nm. The results of the electrochemical analysis reveal that the electrochemical active surface area (ECSA) of Pt/HLPC is larger than the Pt NP electrocatalyst supported on the carbon black (Pt/Vulcan XC-72). Compared with the Pt/Vulcan XC-72, the Pt/HLPC exhibits larger current density, lower overpotential, and enhanced catalytic activity toward the oxygen reduction reaction (ORR) through the direct four-electron pathway. The improved catalytic activity is mainly attributed to the high BET specific surface area, hierarchical porous structures and the nitrogen-doped surface property of HLPC, indicating the superiority of HLPC as a promising support material for the ORR electrocatalysts.

Sodium-ion supercapacitors based on nanoporous pyroproteins containing redox-active heteroatoms

NASA Astrophysics Data System (ADS)

Cho, Se Youn; Yoon, Hyeon Ji; Kim, Na Rae; Yun, Young Soo; Jin, Hyoung-Joon

2016-10-01

Nanostructured carbon-based materials fabricated via simple methods from renewable bio-resources have great potential in rechargeable energy storage systems. In this study, nanoporous pyroproteins containing a large amount of redox-active heteroatoms (H-NPs) were fabricated from silk fibroin by an in situ carbonization/activation method. The H-NPs have a large surface area of ∼3050 m2 g-1, which is mainly comprised of nanometer-scale pores. Also, these H-NPs have oxygen and nitrogen heteroatoms of 17.4 wt% and 2.9 wt%, respectively. Synergistic sodium ion storage behaviors originate from electrochemical double layer capacitance and pseudocapacitance, leading to very high electrochemical performances of H-NPs in aqueous and non-aqueous electrolyte systems. Sodium-ion supercapacitors (NISs) based on commercial graphite//H-NPs show a high specific power of ∼1900 W kg-1 at ∼77 Wh kg-1. Also, NISs based on commercial hard carbon//H-NPs exhibit a high specific energy of ∼217 Wh kg-1 at ∼42 W kg-1. In addition, outstanding cycling performances over 30,000 cycles are achieved for symmetric NISs.

700 F hybrid capacitors cells composed of activated carbon and Li4Ti5O12 microspheres with ultra-long cycle life

NASA Astrophysics Data System (ADS)

Ruan, Dianbo; Kim, Myeong-Seong; Yang, Bin; Qin, Jun; Kim, Kwang-Bum; Lee, Sang-Hyun; Liu, Qiuxiang; Tan, Lei; Qiao, Zhijun

2017-10-01

To address the large-scale application demands of high energy density, high power density, and long cycle lifetime, 700-F hybrid capacitor pouch cells have been prepared, comprising ∼240-μm-thick activated carbon cathodes, and ∼60-μm-thick Li4Ti5O12 anodes. Microspherical Li4Ti5O12 (M-LTO) synthesized by spray-drying features 200-400 nm primary particles and interconnected nanopore structures. M-LTO half-cells exhibits high specific capacities (175 mAhh g-1), good rate capabilities (148 mAhh g-1 at 20 C), and ultra-long cycling stabilities (90% specific capacity retention after 10,000 cycles). In addition, the obtained hybrid capacitors comprising activated carbon (AC) and M-LTO shows excellent cell performances, achieving a maximum energy density of 51.65 Wh kg-1, a maximum power density of 2466 W kg-1, and ∼92% capacitance retention after 10,000 cycles, thus meeting the demands for large-scale applications such as trolleybuses.

Nuclear and analytical methods for investigation of high quality wines

NASA Astrophysics Data System (ADS)

Tonev, D.; Geleva, E.; Grigorov, T.; Goutev, N.; Protohristov, H.; Stoyanov, Ch; Bashev, V.; Tringovska, I.; Kostova, D.

2018-05-01

Nuclear and analytical methods can help to determine the year of production – vintage and the geographical provenance of high quality wines. A complex analytical investigation of Melnik fine wines from “Artarkata” vineyards, Vinogradi village near Melnik in Southwest Bulgaria using different methods and equipment were performed. Nuclear methods, based on measured gamma-ray activity of 137Cs and specific activity of 3H can be used to determine the year of wine production. The specific activity of 137Cs was measured in wines from different vintages using Low-Background High-Resolution Gamma-Spectrometry. Tritium measurements in wine samples were carried out by using a low level liquid scintillation counting in a Packard Tri-Carb 2770 TR/SL liquid scintillation analyzer. The identification of the origin of wines using their chemical fingerprints is of great interest for wine consumers and producers. Determination of 16 chemical elements in samples from soil, wine stems, wine leaves and fine wine from the type Shiroka Melnishka, which are grown in typical Melnik vineyard was made, using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES).

Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity

NASA Astrophysics Data System (ADS)

Zhai, Jiali; Scoble, Judith A.; Li, Nan; Lovrecz, George; Waddington, Lynne J.; Tran, Nhiem; Muir, Benjamin W.; Coia, Gregory; Kirby, Nigel; Drummond, Calum J.; Mulet, Xavier

2015-02-01

Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay. Electronic supplementary information (ESI) available: Fig. S1-S4. See DOI: 10.1039/c4nr05200e

Combination of lentivector immunization and low-dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity.

PubMed

Sierro, Sophie R; Donda, Alena; Perret, Rachel; Guillaume, Philippe; Yagita, Hideo; Levy, Frédéric; Romero, Pedro

2011-08-01

In the last two decades, anti-cancer vaccines have yielded disappointing clinical results despite the fact that high numbers of self/tumor-specific T cells can be elicited in immunized patients. Understanding the reasons behind this lack of efficacy is critical in order to design better treatment regimes. Recombinant lentivectors (rLVs) have been successfully used to induce antigen-specific T cells to foreign or mutated tumor antigens. Here, we show that rLV expressing a murine nonmutated self/tumor antigen efficiently primes large numbers of self/tumor-specific CD8(+) T cells. In spite of the large number of tumor-specific T cells, however, no anti-tumor activity could be measured in a therapeutic setting, in mice vaccinated with rLV. Accumulating evidence shows that, in the presence of malignancies, inhibition of T-cell activity may predominate overstimulation. Analysis of tumor-infiltrating lymphocytes revealed that specific anti-tumor CD8(+) T cells fail to produce cytokines and express high levels of inhibitory receptors such as programmed death (PD)-1. Association of active immunization with chemotherapy or antibodies that block inhibitory pathways often leads to better anti-tumor effects. We show here that combining rLV vaccination with either cyclophosphamide or PD-1 and PD-L1 blocking antibodies enhances rLV vaccination efficacy and improves anti-tumor immunity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

STATUS OF EPA/DOE MOU TECHNICAL WORKGROUP ACTIVITIES: HG WASTE TREATMENT

EPA Science Inventory

EPA's Land Disposal Restrictions program currently has technology-specific treatment standards for hazardous wastes containing greater than or equal to 260ppm total mercury (Hg) (i.e., high Hg subcategory wastes). The treatment standards specify RMERC for high Hg subcategory wast...

Effects of pore structure and electrolyte on the capacitive characteristics of steam- and KOH-activated carbons for supercapacitors

NASA Astrophysics Data System (ADS)

Wu, Feng-Chin; Tseng, Ru-Ling; Hu, Chi-Chang; Wang, Chen-Ching

Four kinds of activated carbons (denoted as ACs) with specific surface area of ca. 1050 m 2 g -1 were fabricated from fir wood and pistachio shell by means of steam activation or chemical activation with KOH. Pore structures of ACs were characterized by a t-plot method based on N 2 adsorption isotherms. The amount of mesopores within KOH-activated carbons ranged from 9.2 to 15.3% while 33.3-49.5% of mesopores were obtained for the steam-activated carbons. The pore structure, surface functional groups, and raw materials of ACs, as well as pH and the supporting electrolyte were also found to be significant factors determining the capacitive characteristics of ACs. The excellent capacitive characteristics in both acidic and neutral media and the weak dependence of the specific capacitance on the scan rate of cyclic voltammetry (CV) for the ACs derived from the pistachio shell with steam activation (denoted as P-H 2O-AC) revealed their promising potential in the application of supercapacitors. The ACs derived from fir wood with KOH activation (denoted as F-KOH-AC), on the other hand, showed the best capacitive performance in H 2SO 4 due to excellent reversibility and high specific capacitance (180 F g -1 measured at 10 mV s -1), which is obviously larger than 100 F g -1 (a typical value of activated carbons with specific surface areas equal to/above 1000 m 2 g -1).

Loss of Consciousness Is Associated with Stabilization of Cortical Activity

PubMed Central

Solovey, Guillermo; Alonso, Leandro M.; Yanagawa, Toru; Fujii, Naotaka; Magnasco, Marcelo O.; Cecchi, Guillermo A.

2015-01-01

What aspects of neuronal activity distinguish the conscious from the unconscious brain? This has been a subject of intense interest and debate since the early days of neurophysiology. However, as any practicing anesthesiologist can attest, it is currently not possible to reliably distinguish a conscious state from an unconscious one on the basis of brain activity. Here we approach this problem from the perspective of dynamical systems theory. We argue that the brain, as a dynamical system, is self-regulated at the boundary between stable and unstable regimes, allowing it in particular to maintain high susceptibility to stimuli. To test this hypothesis, we performed stability analysis of high-density electrocorticography recordings covering an entire cerebral hemisphere in monkeys during reversible loss of consciousness. We show that, during loss of consciousness, the number of eigenmodes at the edge of instability decreases smoothly, independently of the type of anesthetic and specific features of brain activity. The eigenmodes drift back toward the unstable line during recovery of consciousness. Furthermore, we show that stability is an emergent phenomenon dependent on the correlations among activity in different cortical regions rather than signals taken in isolation. These findings support the conclusion that dynamics at the edge of instability are essential for maintaining consciousness and provide a novel and principled measure that distinguishes between the conscious and the unconscious brain. SIGNIFICANCE STATEMENT What distinguishes brain activity during consciousness from that observed during unconsciousness? Answering this question has proven difficult because neither consciousness nor lack thereof have universal signatures in terms of most specific features of brain activity. For instance, different anesthetics induce different patterns of brain activity. We demonstrate that loss of consciousness is universally and reliably associated with stabilization of cortical dynamics regardless of the specific activity characteristics. To give an analogy, our analysis suggests that loss of consciousness is akin to depressing the damper pedal on the piano, which makes the sounds dissipate quicker regardless of the specific melody being played. This approach may prove useful in detecting consciousness on the basis of brain activity under anesthesia and other settings. PMID:26224868

Loss of Consciousness Is Associated with Stabilization of Cortical Activity.

PubMed

Solovey, Guillermo; Alonso, Leandro M; Yanagawa, Toru; Fujii, Naotaka; Magnasco, Marcelo O; Cecchi, Guillermo A; Proekt, Alex

2015-07-29

What aspects of neuronal activity distinguish the conscious from the unconscious brain? This has been a subject of intense interest and debate since the early days of neurophysiology. However, as any practicing anesthesiologist can attest, it is currently not possible to reliably distinguish a conscious state from an unconscious one on the basis of brain activity. Here we approach this problem from the perspective of dynamical systems theory. We argue that the brain, as a dynamical system, is self-regulated at the boundary between stable and unstable regimes, allowing it in particular to maintain high susceptibility to stimuli. To test this hypothesis, we performed stability analysis of high-density electrocorticography recordings covering an entire cerebral hemisphere in monkeys during reversible loss of consciousness. We show that, during loss of consciousness, the number of eigenmodes at the edge of instability decreases smoothly, independently of the type of anesthetic and specific features of brain activity. The eigenmodes drift back toward the unstable line during recovery of consciousness. Furthermore, we show that stability is an emergent phenomenon dependent on the correlations among activity in different cortical regions rather than signals taken in isolation. These findings support the conclusion that dynamics at the edge of instability are essential for maintaining consciousness and provide a novel and principled measure that distinguishes between the conscious and the unconscious brain. What distinguishes brain activity during consciousness from that observed during unconsciousness? Answering this question has proven difficult because neither consciousness nor lack thereof have universal signatures in terms of most specific features of brain activity. For instance, different anesthetics induce different patterns of brain activity. We demonstrate that loss of consciousness is universally and reliably associated with stabilization of cortical dynamics regardless of the specific activity characteristics. To give an analogy, our analysis suggests that loss of consciousness is akin to depressing the damper pedal on the piano, which makes the sounds dissipate quicker regardless of the specific melody being played. This approach may prove useful in detecting consciousness on the basis of brain activity under anesthesia and other settings. Copyright © 2015 the authors 0270-6474/15/3510866-12$15.00/0.

Task-specific Dystonias

PubMed Central

Torres-Russotto, Diego; Perlmutter, Joel S.

2009-01-01

Task-specific dystonias are primary focal dystonias characterized by excessive muscle contractions producing abnormal postures during selective motor activities that often involve highly skilled, repetitive movements. Historically these peculiar postures were considered psychogenic but have now been classified as forms of dystonia. Writer’s cramp is the most commonly identified task-specific dystonia and has features typical of this group of disorders. Symptoms may begin with lack of dexterity during performance of a specific motor task with increasingly abnormal posturing of the involved body part as motor activity continues. Initially, the dystonia may manifest only during the performance of the inciting task, but as the condition progresses it may also occur during other activities or even at rest. Neurological exam is usually unremarkable except for the dystonia-related abnormalities. Although the precise pathophysiology remains unclear, increasing evidence suggests reduced inhibition at different levels of the sensorimotor system. Symptomatic treatment options include oral medications, botulinum toxin injections, neurosurgical procedures, and adaptive strategies. Prognosis may vary depending upon body part involved and specific type of task affected. Further research may reveal new insights into the etiology, pathophysiology, natural history, and improved treatment of these conditions. PMID:18990127

Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators.

PubMed

Polstein, Lauren R; Perez-Pinera, Pablo; Kocak, D Dewran; Vockley, Christopher M; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A

2015-08-01

Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. © 2015 Polstein et al.; Published by Cold Spring Harbor Laboratory Press.

In-vitro engineering of novel bioactivity in the natural enzymes

NASA Astrophysics Data System (ADS)

Tiwari, Vishvanath

2016-10-01

Enzymes catalyze various biochemical functions with high efficiency and specificity. In-vitro design of the enzyme leads to novel bioactivity in this natural biomolecule that give answers of some vital questions like crucial residues in binding with substrate, molecular evolution, cofactor specificity etc. Enzyme engineering technology involves directed evolution, rational designing, semi-rational designing and structure-based designing using chemical modifications. Similarly, combined computational and in-vitro evolution approaches together help in artificial designing of novel bioactivity in the natural enzyme. DNA shuffling, error prone PCR and staggered extension process are used to artificially redesign active site of enzyme, which can alter its efficiency and specificity. Modifications of the enzyme can lead to the discovery of new path of molecular evolution, designing of efficient enzymes, locating active sites and crucial residues, shift in substrate and cofactor specificity. The methods and thermodynamics of in-vitro designing of the enzyme are also discussed. Similarly, engineered thermophilic and psychrophilic enzymes attain substrate specificity and activity of mesophilic enzymes that may also be beneficial for industry and therapeutics.

Validity of questions about activities of daily living to screen for dependency in older adults

PubMed Central

Rebouças, Monica; Coelho-Filho, João Macedo; Veras, Renato Peixoto; Lima-Costa, Maria Fernanda; Ramos, Luiz Roberto

2017-01-01

ABSTRACT OBJECTIVE To determine the criterion validity of the activities of daily living present in functionality questionnaires in older adults for population surveys and to identify which activities are valid to quantify the real daily need for help of this population. METHODS This is a population sample of older adults stratified by levels of functionality, according to self-perception of dependency in the activities of daily living. Self-perception was compared with the gold standard – direct observation of these activities in the household of older adults by a trained professional, blinded to the answers in the questionnaire. At the visit, it was decided if the older adult needed help to perform any of the activities of daily living for the research. The sensitivity of each activity of daily living was greater when the self-assessment that there was no need for help coincided with the assessment of the professional. Specificity indicates coincidence regarding the need for help in the activities of daily living – coefficients of sensitivity and specificity above 70% were considered as indicative of good validity. RESULTS Self-assessments showed better sensitivity than specificity – older adults and observers agreed more on daily independency than on dependency. All activities showed sensitivity above 70%. Some activities had low (go shopping: 55%) or very low specificity (brush the hair: 33%). The best specificities were to take a shower and dress up (95.8% for both), among the personal ones, and to use transportation and perform banking transactions (78% for both), among the instrumental ones. CONCLUSIONS Activities of daily living can be valid indicators of functional dependence. The best coefficients of validity were generally obtained for personal activities. Some activities with good sensitivities and specificities – walk 100 meters, take a shower, and lie down in and get out of the bed – can be used to classify older adults into low, average, and high need for help depending on the affected activities and, therefore, can help in the planning of health services aimed at them. PMID:28876414

Immobilization, Regiospecificity Characterization and Application of Aspergillus oryzae Lipase in the Enzymatic Synthesis of the Structured Lipid 1,3-Dioleoyl-2-Palmitoylglycerol.

PubMed

Cai, Haiying; Li, Yang; Zhao, Minjie; Fu, Guanwen; Lai, Jia; Feng, Fengqin

2015-01-01

The enzymatic synthesis of 1,3-dioleoyl-2-palmitoylglycerol (OPO), one of the main components of human milk fats, has been hindered by the relatively high cost of sn-1,3-specific lipases and the deficiency in biocatalyst stability. The sn-1,3-specific lipase from Aspergillus oryzae (AOL) is highly and efficiently immobilized with the polystyrene-based hydrophobic resin D3520, with a significant 49.54-fold increase in specific lipase activity compared with the AOL powder in catalyzing the synthesis of OPO through the acidolysis between palm stearin and oleic acid (OA). The optimal immobilization conditions were investigated, including time course, initial protein concentration and solution pH. The sn-1,3 specificity of lipases under different immobilization conditions was evaluated and identified as positively associated with the lipase activity, and the pH of the immobilization solution influenced the regiospecificity and synthetic activity of these lipases. Immobilized AOL D3520, as the biocatalyst, was used for the enzymatic synthesis of the structured lipid OPO through the acidolysis between palm stearin and OA. The following conditions were optimized for the synthesis of structured lipid OPO: 65 °C temperature; 1:8 substrate molar ratio between palm stearin and OA; 8% (w/w) enzyme load; 3.5% water content of the immobilized lipase; and 1 h reaction time. Under these conditions, highly efficient C52 production (45.65%) was achieved, with a tripalmitin content of 2.75% and a sn-2 palmitic acid (PA) proportion of 55.08% in the system.

Probing the Effector and Suppressive Functions of Human T Cell Subsets Using Antigen-Specific Engineered T Cell Receptors

PubMed Central

Imberg, Keren; Mercer, Frances; Zhong, Shi; Krogsgaard, Michelle; Unutmaz, Derya

2013-01-01

Activation of T cells through the engagement of the T cell receptors (TCRs) with specific peptide-MHC complexes on antigen presenting cells (APCs) is the major determinant for their proliferation, differentiation and display of effector functions. To assess the role of quantity and quality of peptide-MHC presentation in eliciting T cell activation and suppression functions, we genetically engineered human T cells with two TCRs that recognize HLA-A*0201-restricted peptides derived from either HIV or melanoma antigens. The engineered-TCRs are highly functional in both CD8+ and CD4+ T cells as assessed by the upregulation of activation markers, induction of cytokine secretion and cytotoxicity. We further demonstrated that engineered-TCRs can also be expressed on naïve human T cells, which are stimulated through APCs presenting specific peptides to induce T cell proliferation and acquire effector functions. Furthermore, regulatory T cells (Tregs) ectopically expressing the engineered-TCRs are activated in an antigen-specific fashion and suppress T cell proliferation. In this system, the inhibitory activity of peptide-stimulated Tregs require the presence of dendritic cells (DCs) in the culture, either as presenters or as bystander cells, pointing to a critical role for DCs in suppression by Tregs. In conclusion, the engineered-TCR system reported here advances our ability to understand the differentiation pathways of naïve T cells into antigen-specific effector cells and the role of antigen-specific signaling in Treg-mediated immune suppression. PMID:23437112

Structure-activity relationships of 4-hydroxyalkenals in the conjugation catalysed by mammalian glutathione transferases.

PubMed Central

Danielson, U H; Esterbauer, H; Mannervik, B

1987-01-01

The substrate specificities of 15 cytosolic glutathione transferases from rat, mouse and man have been explored by use of a homologous series of 4-hydroxyalkenals, extending from 4-hydroxypentenal to 4-hydroxypentadecenal. Rat glutathione transferase 8-8 is exceptionally active with the whole range of 4-hydroxyalkenals, from C5 to C15. Rat transferase 1-1, although more than 10-fold less efficient than transferase 8-8, is the second most active transferase with the longest chain length substrates. Other enzyme forms showing high activities with these substrates are rat transferase 4-4 and human transferase mu. The specificity constants, kcat./Km, for the various enzymes have been determined with the 4-hydroxyalkenals. From these constants the incremental Gibbs free energy of binding to the enzyme has been calculated for the homologous substrates. The enzymes responded differently to changes in the length of the hydrocarbon side chain and could be divided into three groups. All glutathione transferases displayed increased binding energy in response to increased hydrophobicity of the substrate. For some of the enzymes, steric limitations of the active site appear to counteract the increase in binding strength afforded by increased chain length of the substrate. Comparison of the activities with 4-hydroxyalkenals and other activated alkenes provides information about the active-site properties of certain glutathione transferases. The results show that the ensemble of glutathione transferases in a given species may serve an important physiological role in the conjugation of the whole range of 4-hydroxyalkenals. In view of its high catalytic efficiency with all the homologues, rat glutathione transferase 8-8 appears to have evolved specifically to serve in the detoxication of these reactive compounds of oxidative metabolism. PMID:3426557

Aminopyrazinamides: novel and specific GyrB inhibitors that kill replicating and nonreplicating Mycobacterium tuberculosis.

PubMed

Shirude, Pravin S; Madhavapeddi, Prashanti; Tucker, Julie A; Murugan, Kannan; Patil, Vikas; Basavarajappa, Halesha; Raichurkar, Anandkumar V; Humnabadkar, Vaishali; Hussein, Syeed; Sharma, Sreevalli; Ramya, V K; Narayan, Chandan B; Balganesh, Tanjore S; Sambandamurthy, Vasan K

2013-03-15

Aminopyrazinamides originated from a high throughput screen targeting the Mycobacterium smegmatis (Msm) GyrB ATPase. This series displays chemical tractability, robust structure-activity relationship, and potent antitubercular activity. The crystal structure of Msm GyrB in complex with one of the aminopyrazinamides revealed promising attributes of specificity against other broad spectrum pathogens and selectivity against eukaryotic kinases due to novel interactions at hydrophobic pocket, unlike other known GyrB inhibitors. The aminopyrazinamides display excellent mycobacterial kill under in vitro, intracellular, and hypoxic conditions.

High specific activity platinum-195m

DOEpatents

Mirzadeh, Saed; Du, Miting; Beets, Arnold L.; Knapp, Jr., Furn F.

2004-10-12

A new composition of matter includes .sup.195m Pt characterized by a specific activity of at least 30 mCi/mg Pt, generally made by method that includes the steps of: exposing .sup.193 Ir to a flux of neutrons sufficient to convert a portion of the .sup.193 Ir to .sup.195m Pt to form an irradiated material; dissolving the irradiated material to form an intermediate solution comprising Ir and Pt; and separating the Pt from the Ir by cation exchange chromatography to produce .sup.195m Pt.

Erythroid activator NF-E2, TAL1 and KLF1 play roles in forming the LCR HSs in the human adult β-globin locus.

PubMed

Kim, Yea Woon; Yun, Won Ju; Kim, AeRi

2016-06-01

The β-like globin genes are developmental stage specifically transcribed in erythroid cells. The transcription of the β-like globin genes requires erythroid specific activators such as GATA-1, NF-E2, TAL1 and KLF1. However, the roles of these activators have not fully elucidated in transcription of the human adult β-globin gene. Here we employed hybrid MEL cells (MEL/ch11) where a human chromosome containing the β-globin locus is present and the adult β-globin gene is highly transcribed by induction. The roles of erythroid specific activators were analyzed by inhibiting the expression of NF-E2, TAL1 or KLF1 in MEL/ch11 cells. The loss of each activator decreased the transcription of human β-globin gene, locus wide histone hyperacetylation and the binding of other erythroid specific activators including GATA-1, even though not affecting the expression of other activators. Notably, sensitivity to DNase I was reduced in the locus control region (LCR) hypersensitive sites (HSs) with the depletion of activators. These results indicate that NF-E2, TAL1 and KLF1, all activators play a primary role in HSs formation in the LCR. It might contribute to the transcription of human adult β-globin gene by allowing the access of activators and cofactors. The roles of activators in the adult β-globin locus appear to be different from the roles in the early fetal locus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

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

Morrison, W.J.

1988-01-01

The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF ormore » thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).« less

[Isolation and characterization of vaginal lactobacilli producing hydrogen peroxide].

PubMed

Pashaian, M M; Oganesian, G G

2011-01-01

Isolation and characteristics of vaginal lactobacilli that actively generate H2O2 and have high antagonistic activity. Staphylococcus aureus 8956, Escherichia coli 8852, Klebsiella pneumoniae 8795 and Candida albicans 5646 were used as target-strains. Skim milk and MRS medium were used for lactobacilli isolation and cultivation. Antagonism was studied in complete agar and Saburo medium. Merckoquant peroxide test (Merck) stripes were used for the determination of H2O2. Antibacterial activity was determined by diffusion into agar. Specific culture growth rate was determined by conventional method, acidification of the culture medium--by pH-meter. 12 strains were isolated from vaginal smears of healthy women. These strains have an ability to ferment milk among which a highly active H2O2 producer was isolated and attributed to Lactobacillus delbrueckii by the results of 16S rRNA and alpha-subunit RNA polymerase gene sequence analysis (16S rDNA and rpoA genes are registered in GenBank, numbers HQ379171 and HQ379180 respectively). L. delbrueckii MH-10 bacterial cells were characterized by specific growth speed 1.26 per hour, reaching a maximum titer of 2 x 10(9) PFU/ml with lowering medium pH to 4.0. Under aerated conditions H2O2 concentration reached 100 microg/ml or more. L. delbrueckii MH-10 has high antibacterial activity against S. aureus, E. coli, K. pneumoniae. L. delbrueckii MH-10 isolate is an active H2O2 producer, has high growth speed and broad antibacterial activity spectrum, is a perspective candidate for the development of probiotic preparation for the prophylaxis and therapy of vaginoses.

Alteration of high and low spin equilibrium by a single mutation of amino acid 209 in mouse cytochromes P450.

PubMed

Iwasaki, M; Juvonen, R; Lindberg, R; Negishi, M

1991-02-25

The identities of the amino acid at position 209 are most critical in determining specific coumarin 7- and steroid 15 alpha-hydroxylase activity in P450coh and P450(15)alpha, respectively. This system, therefore, provides us with an excellent model to study the structural basis for P450 specificity as a monooxygenase. We expressed in Saccharomyces cerevisiae a series of the mutated P450s in which residue 209 was substituted with the various amino acids and characterized the spectral property and hydroxylase activity of these mutated P450s. The positioning of a hydrophobic residue including Phe, Leu, and Val at position 209 resulted in shifting the P450 to the high-spin state, while a charged amino acid such as Lys or Asp produced the low-spin form. Moreover, a P450 with Asn or Gly in this position exhibited spectra indicating a mixture of the high- and low-spin forms. This spin alteration, depending upon the hydrophobicity and size of residue at position 209, indicates that this position is likely to reside close to the sixth axial ligand on the distal surface of the heme in these P450s. This proximity of residue 209 to the ligand may explain the critical role of this residue in determining the hydroxylase specificity and activity of these P450s.

Phagocytosis and Respiratory Burst Activity in Lumpsucker (Cyclopterus lumpus L.) Leucocytes Analysed by Flow Cytometry

PubMed Central

Haugland, Gyri T.; Jakobsen, Ragnhild Aakre; Vestvik, Nils; Ulven, Kristian; Stokka, Lene; Wergeland, Heidrun I.

2012-01-01

In the present study, we have isolated leucocytes from peripheral blood, head kidney and spleen from lumpsucker (Cyclopterus lumpus L.), and performed functional studies like phagocytosis and respiratory burst, as well as morphological and cytochemical analyses. Different leucocytes were identified, such as lymphocytes, monocytes/macrophages and polymorphonuclear cells with bean shaped or bilobed nuclei. In addition, cells with similar morphology as described for dendritic cells in trout were abundant among the isolated leucocytes. Flow cytometry was successfully used for measuring phagocytosis and respiratory burst activity. The phagocytic capacity and ability were very high, and cells with different morphology in all three leucocyte preparations phagocytised beads rapidly. Due to lack of available cell markers, the identity of the phagocytic cells could not be determined. The potent non-specific phagocytosis was in accordance with a high number of cells positive for myeloperoxidase, an enzyme involved in oxygen-dependent killing mechanism present in phagocytic cells. Further, high respiratory burst activity was present in the leucocytes samples, verifying a potent oxygen- dependent degradation. At present, the specific antibody immune response could not be measured, as immunoglobulin or B-cells have not yet been isolated. Therefore, analyses of the specific immune response in this fish species await further clarification. The present study presents the first analyses of lumpsucker immunity and also the first within the order Scopaeniformes. PMID:23112870

Topographical differences of frontal-midline theta activity reflect functional differences in cognitive control abilities.

PubMed

Eschmann, Kathrin C J; Bader, Regine; Mecklinger, Axel

2018-06-01

Electrophysiological oscillations are assumed to be the core mechanism for large-scale network communication. The specific role of frontal-midline theta oscillations as cognitive control mechanism is under debate. According to the dual mechanisms of control framework, cognitive control processes can be divided into proactive and reactive control. The present study aimed at investigating the role of frontal-midline theta activity by assessing oscillations in two tasks varying in the type of cognitive control needed. More specifically, a delayed match to sample (DMTS) task requiring proactive control and a color Stroop task recruiting reactive control processes were conducted within the same group of participants. Moreover, both tasks contained conditions with low and high need for cognitive control. As expected larger frontal-midline theta activity was found in conditions with high need for cognitive control. However, theta activity was focally activated at frontal sites in the DMTS task whereas it had a broader topographical distribution in the Stroop task, indicating that both proactive and reactive control are reflected in frontal-midline theta activity but reactive control is additionally characterized by a broader theta activation. These findings support the conclusion that frontal-midline theta acts functionally different depending on task requirements. Copyright © 2018 Elsevier Inc. All rights reserved.

Nano-aggregates: emerging delivery tools for tumor therapy.

PubMed

Sharma, Vinod Kumar; Jain, Ankit; Soni, Vandana

2013-01-01

A plethora of formulation techniques have been reported in the literature for site-specific targeting of water-soluble and -insoluble anticancer drugs. Along with other vesicular and particulate carrier systems, nano-aggregates have recently emerged as a novel supramolecular colloidal carrier with promise for using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates possess some inherent properties such as size in the nanometers, high loading efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug delivery via either a passive or active targeting mechanism. Nano-aggregates are formed from a polymer-drug conjugated amphiphilic block copolymer. They are suitable for encapsulation of poorly water-soluble drugs by covalent conjugation as well as physical encapsulation. Because of physical encapsulation, a maximum amount of drug can be loaded in nano-aggregates, which helps to achieve a sufficiently high drug concentration at the target site. Active transport can be achieved by conjugating a drug with vectors or ligands that bind specifically to receptors being overexpressed in the tumor cells. In this review, we explore synthesis and tumor targeting potential of nano-aggregates with active and passive mechanisms, and we discuss various characterization parameters, ex vivo studies, biodistribution studies, clinical trials, and patents.

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

PubMed

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

2011-01-01

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

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

PubMed

Rockah-Shmuel, Liat; Tawfik, Dan S

2012-12-01

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

Nitrogen-Doped Porous Carbons As Electrode Materials for High-Performance Supercapacitor and Dye-Sensitized Solar Cell.

PubMed

Wang, Lan; Gao, Zhiyong; Chang, Jiuli; Liu, Xiao; Wu, Dapeng; Xu, Fang; Guo, Yuming; Jiang, Kai

2015-09-16

Activated N-doped porous carbons (a-NCs) were synthesized by pyrolysis and alkali activation of graphene incorporated melamine formaldehyde resin (MF). The moderate N doping levels, mesopores rich porous texture, and incorporation of graphene enable the applications of a-NCs in surface and conductivity dependent electrode materials for supercapacitor and dye-sensitized solar cell (DSSC). Under optimal activation temperature of 700 °C, the afforded sample, labeled as a-NC700, possesses a specific surface area of 1302 m2 g(-1), a N fraction of 4.5%, and a modest graphitization. When used as a supercapacitor electrode, a-NC700 offers a high specific capacitance of 296 F g(-1) at a current density of 1 A g(-1), an acceptable rate capability, and a high cycling stability in 1 M H2SO4 electrolyte. As a result, a-NC700 supercapacitor delivers energy densities of 5.0-3.5 Wh kg(-1) under power densities of 83-1609 W kg(-1). Moreover, a-NC700 also demonstrates high electrocatalytic activity for I3- reduction. When employed as a counter electrode (CE) of DSSC, a power conversion efficiency (PCE) of 6.9% is achieved, which is comparable to that of the Pt CE based counterpart (7.1%). The excellent capacitive and photovoltaic performances highlight the potential of a-NCs in sustainable energy devices.

Neurotrophic factor - Characterization and partial purification

NASA Technical Reports Server (NTRS)

Popiela, H.; Ellis, S.

1981-01-01

Recent evidence suggests that neurotrophic activity is required for the normal proliferation and development of muscle cells. The present paper reports a study of the purification and characterization of a neurotrophic factor (NTF) from adult chicken ischiatic-peroneal nerves using two independent quantitative in vitro assay systems. The assays were performed by the measurement of the incorporation of tritiated thymidine or the sizes of single-cell clones by chick muscle cells grown in culture. The greatest amount of neutrotrophic activity is found to be extracted at a pH of 8; aqueous suspensions of the activity are stable to long-term storage at room temperature. The specific activity of the substance is doubled upon precipitation with ammonium sulfate or after gel filtration, and increase 4 to 5 fold after salt gradient elution from DEAE cellulose columns. The active fraction obtained after gel filtration and rechromatography on DEAE cellulose exhibits a 7 to 10-fold increase in specific activity. Electrophoresis of the most highly purified material yields a greatly concentrated band at around 80,000 daltons. Although NTF is purified almost 10-fold as indicated by the increase in specific activity, the maximum activity of the partially purified material is greatly reduced, possibly due to a requirement for a cofactor for the expression of maximum activity.

Metabolic syndrome and hypertension: regular exercise as part of lifestyle management.

PubMed

Lackland, Daniel T; Voeks, Jenifer H

2014-11-01

The incorporation of physical activity and exercise represents a clinically important aspect in the management of metabolic syndrome, hypertension, and diabetes. While the benefit of exercise and active lifestyles is well documented for prevention and risk reduction of cardiovascular and stroke outcomes, the detailed regiment and recommendations are less clear. The components of a prescribed physical activity include consideration of activity type, frequency of an activity, activity duration, and intensity of a specific physical movement. The exercise parameters prescribed as part of the management of metabolic syndrome, diabetes, and elevated blood pressure are most often proposed as separate documents while the general recommendations are similar. The evidence is strong such that physical activity and exercise recommendations in disease management guidelines are considered high quality. The general recommendations for both blood pressure and glycemic management include a regiment of physical activity with moderate- to high-intensity exercise of 30-min bouts on multiple days with a desired goal of a total of 150 min of exercise per week. While additional research is needed to identify the specific exercise/activity mode, frequencies for exercise training, intensity levels, and duration of exercise that achieve maximal blood pressure and glycemic lowering, this general recommendation showed a consistent and significant benefit in risk reduction. Similarly, the current available evidence also indicates that aerobic exercise, dynamic resistance exercise, and isometric exercises can lower blood pressure and improve glycemic control.

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

PubMed Central

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

2011-01-01

Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime period, general event, and event-specific). Sixteen young adults participated in a neuroimaging study in which they retrieved autobiographical memories associated with musical cues. These musical cues led to the retrieval of highly emotional memories that had low levels of prior retrieval. Retrieval of all autobiographical memory levels was associated with activity in regions in the autobiographical memory network, specifically the ventromedial prefrontal cortex, posterior cingulate, and right medial temporal lobe. Owing to the use of music, memories from varying levels of specificity were retrieved, allowing for comparison of event memory and abstract personal knowledge, as well as comparison of specific and general event memory. Dorsolateral and dorsomedial prefrontal regions were engaged during event retrieval relative to personal knowledge retrieval, and retrieval of specific event memories was associated with increased activity in the bilateral medial temporal lobe and dorsomedial prefrontal cortex relative to retrieval of general event memories. These results suggest that the initial search processes for memories of different specificity levels preferentially engage different components of the autobiographical memory network. The potential underlying causes of these neural differences are discussed. PMID:21600227

Vaccination Expands Antigen-Specific CD4+ Memory T Cells and Mobilizes Bystander Central Memory T Cells

PubMed Central

Li Causi, Eleonora; Parikh, Suraj C.; Chudley, Lindsey; Layfield, David M.; Ottensmeier, Christian H.; Stevenson, Freda K.; Di Genova, Gianfranco

2015-01-01

CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7RαLow and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7Rα and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines. PMID:26332995

[The high pressure life of piezophiles].

PubMed

Oger, Philippe; Cario, Anaïs

2014-01-01

The deep biosphere is composed of very different biotopes located in the depth of the oceans, the ocean crust or the lithosphere. Although very different, deep biosphere biotopes share one common feature, high hydrostatic pressure. The deep biosphere is colonized by specific organisms, called piezophiles, that are able to grow under high hydrostatic pressure. Bacterial piezophiles are mainly psychrophiles belonging to five genera of γ-proteobacteria, Photobacterium, Shewanella, Colwellia, Psychromonas and Moritella, while piezophilic Archaea are mostly (hyper)thermophiles from the Thermococcales. None of these genera are specific for the deep biosphere. High pressure deeply impacts the activity of cells and cellular components, and reduces the activity of numerous key processes, eventually leading to cell death of piezosensitive organisms. Biochemical and genomic studies yield a fragmented view on the adaptive mechanisms in piezophiles. It is yet unclear whether piezophilic adaptation requires the modification of a few genes, or metabolic pathways, or a more profound reorganization of the genome, the fine tuning of gene expression to compensate the pressure-induced loss of activity of the proteins most affected by high pressure, or a stress-like physiological cell response. In contrast to what has been seen for thermophily or halophily, the adaptation to high pressure is diffuse in the genome and may concern only a small fraction of the genes. © Société de Biologie, 2014.

Combining High-Speed Cameras and Stop-Motion Animation Software to Support Students' Modeling of Human Body Movement

ERIC Educational Resources Information Center

Lee, Victor R.

2015-01-01

Biomechanics, and specifically the biomechanics associated with human movement, is a potentially rich backdrop against which educators can design innovative science teaching and learning activities. Moreover, the use of technologies associated with biomechanics research, such as high-speed cameras that can produce high-quality slow-motion video,…

Social Class and the STEM Career Pipeline an Ethnographic Investigation of Opportunity Structures in a High-Poverty versus Affluent High School

ERIC Educational Resources Information Center

Nikischer, Andrea B.

2013-01-01

This research investigates science, technology, engineering and mathematics (STEM) high school opportunity structures, including student experiences with math and science course sequences and progress, college guidance and counseling, and STEM extracurricular activities (Weis and Eisenhart, 2009), specifically related to STEM fields and career and…

Physical activity barriers and motivators among high-risk employees.

PubMed

Paguntalan, John C; Gregoski, Mathew

2016-11-22

Worksite wellness programs offer an ideal setting to target high-risk sedentary workers to improve health status. Lack of physical activity is associated with increased risk for coronary heart disease and mortality. Despite the risks, the number of sedentary workers is increasing. This study examined the perceived barriers and motivators for physical activity among employees at high-risk for coronary heart disease. A purposive sample of 24 high-risk workers participating in a wellness program in rural South Carolina were enrolled in the study. Qualitative data was obtained through semi-structured face-to-face interviews. Grounded theory was used to analyze qualitative data, and identify overarching themes. Physical limitations due to pain and weakness, lack of motivation, and lack of time emerged as the main barriers to physical activity. Family relationships were reported as the strongest motivator along with social support and potential health benefits. Findings highlight the unique experience of high-risk workers with physical activity. The findingsunderscore the need to design and implement effective interventions specifically designed to meet the needs of high-risk employees.

The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.

PubMed

Zhang, Y; LeRoy, G; Seelig, H P; Lane, W S; Reinberg, D

1998-10-16

Histone acetylation and deacetylation were found to be catalyzed by structurally distinct, multisubunit complexes that mediate, respectively, activation and repression of transcription. ATP-dependent nucleosome remodeling, mediated by different multisubunit complexes, was thought to be involved only in transcription activation. Here we report the isolation of a protein complex that contains both histone deacetylation and ATP-dependent nucleosome remodeling activities. The complex contains the histone deacetylases HDAC1/2, histone-binding proteins, the dermatomyositis-specific autoantigen Mi2beta, a polypeptide related to the metastasis-associated protein 1, and a novel polypeptide of 32 kDa. Patients with dermatomyositis have a high rate of malignancy. The finding that Mi2beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis.

Comparison of content in phenolic compounds, polyphenol oxidase, and peroxidase in grains of fifty sorghum varieties from burkina faso.

PubMed

Dicko, Mamoudou H; Hilhorst, Riet; Gruppen, Harry; Traore, Alfred S; Laane, Colja; van Berkel, Willem J H; Voragen, Alphons G J

2002-06-19

Analysis of fifty sorghum [Sorghum bicolor (L.) Moench] varieties used in Burkina Faso showed that they have different contents of phenolic compounds, peroxidase (POX), and polyphenol oxidase (PPO). Most of the varieties (82%) had a tannin content less than 0.25% (w/w). POX specific activity was higher than the monophenolase and o-diphenolase specific activities of PPO. For POX, there was a diversity of isoforms among varieties. No clear correlation could be made between the quantitative composition of the grain in phenolics, PPO, and POX, and resistance of plant to pathogens. In general, varieties good for a thick porridge preparation ("tô") had low phenolic compounds content and a medium POX activity. From the red varieties, those used for local beer ("dolo") had a high content in phenolic compounds and PPO, and a low POX activity. The variety considered good for couscous had a low POX content. The characteristics might be useful as selection markers for breeding for specific applications.

Does the Sound of a Barking Dog Activate its Corresponding Visual Form? An fMRI Investigation of Modality-Specific Semantic Access

PubMed Central

Reilly, Jamie; Garcia, Amanda; Binney, Richard J.

2016-01-01

Much remains to be learned about the neural architecture underlying word meaning. Fully distributed models of semantic memory predict that the sound of a barking dog will conjointly engage a network of distributed sensorimotor spokes. An alternative framework holds that modality-specific features additionally converge within transmodal hubs. Participants underwent functional MRI while covertly naming familiar objects versus newly learned novel objects from only one of their constituent semantic features (visual form, characteristic sound, or point-light motion representation). Relative to the novel object baseline, familiar concepts elicited greater activation within association regions specific to that presentation modality. Furthermore, visual form elicited activation within high-level auditory association cortex. Conversely, environmental sounds elicited activation in regions proximal to visual association cortex. Both conditions commonly engaged a putative hub region within lateral anterior temporal cortex. These results support hybrid semantic models in which local hubs and distributed spokes are dually engaged in service of semantic memory. PMID:27289210

Radioactivity in trinitite six decades later.

PubMed

Parekh, Pravin P; Semkow, Thomas M; Torres, Miguel A; Haines, Douglas K; Cooper, Joseph M; Rosenberg, Peter M; Kitto, Michael E

2006-01-01

The first nuclear explosion test, named the Trinity test, was conducted on July 16, 1945 near Alamogordo, New Mexico. In the tremendous heat of the explosion, the radioactive debris fused with the local soil into a glassy material named Trinitite. Selected Trinitite samples from ground zero (GZ) of the test site were investigated in detail for radioactivity. The techniques used included alpha spectrometry, high-efficiency gamma-ray spectrometry, and low-background beta counting, following the radiochemistry for selected radionuclides. Specific activities were determined for fission products (90Sr, 137Cs), activation products (60Co, 133Ba, 152Eu, 154Eu, 238Pu, 241Pu), and the remnants of the nuclear fuel (239Pu, 240Pu). Additionally, specific activities of three natural radionuclides (40K, 232Th, 238U) and their progeny were measured. The determined specific activities of radionuclides and their relationships are interpreted in the context of the fission process, chemical behavior of the elements, as well as the nuclear explosion phenomenology.

An Isozyme-specific Redox Switch in Human Brain Glycogen Phosphorylase Modulates Its Allosteric Activation by AMP.

PubMed

Mathieu, Cécile; Duval, Romain; Cocaign, Angélique; Petit, Emile; Bui, Linh-Chi; Haddad, Iman; Vinh, Joelle; Etchebest, Catherine; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-11-11

Brain glycogen and its metabolism are increasingly recognized as major players in brain functions. Moreover, alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. In the brain, both muscle and brain glycogen phosphorylase isozymes regulate glycogen mobilization. However, given their distinct regulatory features, these two isozymes could confer distinct metabolic functions of glycogen in brain. Interestingly, recent proteomics studies have identified isozyme-specific reactive cysteine residues in brain glycogen phosphorylase (bGP). In this study, we show that the activity of human bGP is redox-regulated through the formation of a disulfide bond involving a highly reactive cysteine unique to the bGP isozyme. We found that this disulfide bond acts as a redox switch that precludes the allosteric activation of the enzyme by AMP without affecting its activation by phosphorylation. This unique regulatory feature of bGP sheds new light on the isoform-specific regulation of glycogen phosphorylase and glycogen metabolism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Domain Specific vs Domain General: Implications for Dynamic Assessment

ERIC Educational Resources Information Center

Kaniel, Shlomo

2010-01-01

The article responds to the need for evidence-based dynamic assessment. The article is divided into two sections: In Part 1 we examine the scientific answer to the question of how far human mental activities and capabilities are domain general (DG) / domain specific (DS). A highly complex answer emerges from the literature review of domains such…

Humic acids-based hierarchical porous carbons as high-rate performance electrodes for symmetric supercapacitors.

PubMed

Qiao, Zhi-jun; Chen, Ming-ming; Wang, Cheng-yang; Yuan, Yun-cai

2014-07-01

Two kinds of hierarchical porous carbons (HPCs) with specific surface areas of 2000 m(2)g(-1) were synthesized using leonardite humic acids (LHA) or biotechnology humic acids (BHA) precursors via a KOH activation process. Humic acids have a high content of oxygen-containing groups which enabled them to dissolve in aqueous KOH and facilitated the homogeneous KOH activation. The LHA-based HPC is made up of abundant micro-, meso-, and macropores and in 6M KOH it has a specific capacitance of 178 F g(-1) at 100 Ag(-1) and its capacitance retention on going from 0.05 to 100 A g(-1) is 64%. In contrast, the BHA-based HPC exhibits a lower capacitance retention of 54% and a specific capacitance of 157 F g(-1) at 100 A g(-1) which is due to the excessive micropores in the BHA-HPC. Moreover, LHA-HPC is produced in a higher yield than BHA-HPC (51 vs. 17 wt%). Copyright © 2014 Elsevier Ltd. All rights reserved.

Construction of high-energy-density supercapacitors from pine-cone-derived high-surface-area carbons.

PubMed

Karthikeyan, Kaliyappan; Amaresh, Samuthirapandiyan; Lee, Sol Nip; Sun, Xueliang; Aravindan, Vanchiappan; Lee, Young-Gi; Lee, Yun Sung

2014-05-01

Very high surface area activated carbons (AC) are synthesized from pine cone petals by a chemical activation process and subsequently evaluated as an electrode material for supercapacitor applications in a nonaqueous medium. The maximum specific surface area of ∼3950 m(2)  g(-1) is noted for the material treated with a 1:5 ratio of KOH to pine cone petals (PCC5), which is much higher than that reported for carbonaceous materials derived from various other biomass precursors. A symmetric supercapacitor is fabricated with PCC5 electrodes, and the results showed enhanced supercapacitive behavior with the highest energy density of ∼61 Wh kg(-1). Furthermore, outstanding cycling ability is evidenced for such a configuration, and ∼90 % of the initial specific capacitance after 20,000 cycles under harsh conditions was observed. This result revealed that the pine-cone-derived high-surface-area AC can be used effectively as a promising electrode material to construct high-energy-density supercapacitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly efficient and autocatalytic H2₂ dissociation for CO₂ reduction into formic acid with zinc.

PubMed

Jin, Fangming; Zeng, Xu; Liu, Jianke; Jin, Yujia; Wang, Lunying; Zhong, Heng; Yao, Guodong; Huo, Zhibao

2014-03-28

Artificial photosynthesis, specifically H2O dissociation for CO2 reduction with solar energy, is regarded as one of the most promising methods for sustainable energy and utilisation of environmental resources. However, a highly efficient conversion still remains extremely challenging. The hydrogenation of CO2 is regarded as the most commercially feasible method, but this method requires either exotic catalysts or high-purity hydrogen and hydrogen storage, which are regarded as an energy-intensive process. Here we report a highly efficient method of H2O dissociation for reducing CO2 into chemicals with Zn powder that produces formic acid with a high yield of approximately 80%, and this reaction is revealed for the first time as an autocatalytic process in which an active intermediate, ZnH(-) complex, serves as the active hydrogen. The proposed process can assist in developing a new concept for improving artificial photosynthetic efficiency by coupling geochemistry, specifically the metal-based reduction of H2O and CO2, with solar-driven thermochemistry for reducing metal oxide into metal.

Highly efficient and autocatalytic H2O dissociation for CO2 reduction into formic acid with zinc

PubMed Central

Jin, Fangming; Zeng, Xu; Liu, Jianke; Jin, Yujia; Wang, Lunying; Zhong, Heng; Yao, Guodong; Huo, Zhibao

2014-01-01

Artificial photosynthesis, specifically H2O dissociation for CO2 reduction with solar energy, is regarded as one of the most promising methods for sustainable energy and utilisation of environmental resources. However, a highly efficient conversion still remains extremely challenging. The hydrogenation of CO2 is regarded as the most commercially feasible method, but this method requires either exotic catalysts or high-purity hydrogen and hydrogen storage, which are regarded as an energy-intensive process. Here we report a highly efficient method of H2O dissociation for reducing CO2 into chemicals with Zn powder that produces formic acid with a high yield of approximately 80%, and this reaction is revealed for the first time as an autocatalytic process in which an active intermediate, ZnH− complex, serves as the active hydrogen. The proposed process can assist in developing a new concept for improving artificial photosynthetic efficiency by coupling geochemistry, specifically the metal-based reduction of H2O and CO2, with solar-driven thermochemistry for reducing metal oxide into metal. PMID:24675820

Immunobiology of HPV and HPV vaccines.

PubMed

Stanley, Margaret

2008-05-01

Genital human papillomavirus (HPV) infection with both low- and high-risk types is common, but most infections resolve as a result of a cell-mediated immune response. Failure to induce an effective immune response is related to inefficient activation of innate immunity and ineffective priming of the adaptive immune response; this defective immune response facilitates viral persistence, a key feature of high-risk HPV infection. This milieu becomes operationally HPV antigen tolerant, and the host's defenses become irrevocably compromised. HPV antigen-specific effector cells are poorly recruited to the infected focus and their activity is downregulated; neoplastic HPV containing cervical keratinocytes expressing high levels of E6 and E7 oncoproteins are not killed in this immunosuppressive, tolerant milieu, and progression to high-grade disease and cancer can result. Highly efficacious prophylactic HPV L1 virus-like particle (VLP) vaccines circumvent viral epithelial evasion strategies since they are delivered by intramuscular injection. The stromal dendritic cells of the muscle that encounter the highly immunogenic repeat structure of the VLP then migrate with their cargo to the lymph node, initiating an immune cascade that results in a robust T-cell dependent B-cell response, which generates high levels of L1-specific serum neutralizing antibodies and immune memory.

A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

PubMed

Alten, Leonie; Schuster-Gossler, Karin; Eichenlaub, Michael P; Wittbrodt, Beate; Wittbrodt, Joachim; Gossler, Achim

2012-01-01

The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs) whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC) expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE) upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

Control of Promatrilysin (MMP7) Activation and Substrate-specific Activity by Sulfated Glycosaminoglycans*

PubMed Central

Ra, Hyun-Jeong; Harju-Baker, Susanna; Zhang, Fuming; Linhardt, Robert J.; Wilson, Carole L.; Parks, William C.

2009-01-01

Matrix metalloproteinases are maintained in an inactive state by a bond between the thiol of a conserved cysteine in the prodomain and a zinc atom in the catalytic domain. Once this bond is disrupted, MMPs become active proteinases and can act on a variety of extracellular protein substrates. In vivo, matrilysin (MMP7) activates pro-α-defensins (procryptdins), but in vitro, processing of these peptides is slow, with about 50% conversion in 8–12 h. Similarly, autolytic activation of promatrilysin in vitro can take up to 12–24 h for 50% conversion. These inefficient reactions suggest that natural cofactors enhance the activation and activity of matrilysin. We determined that highly sulfated glycosaminoglycans (GAG), such as heparin, chondroitin-4,6-sulfate (CS-E), and dermatan sulfate, markedly enhanced (>50-fold) the intermolecular autolytic activation of promatrilysin and the activity of fully active matrilysin to cleave specific physiologic substrates. In contrast, heparan sulfate and less sulfated forms of chondroitin sulfate did not augment matrilysin activation or activity. Chondroitin-2,6-sulfate (CS-D) also did not enhance matrilysin activity, suggesting that the presentation of sulfates is more important than the overall degree of sulfation. Surface plasmon resonance demonstrated that promatrilysin bound heparin (KD, 400 nm) and CS-E (KD, 630 nm). Active matrilysin bound heparin (KD, 150 nm) but less so to CS-E (KD, 60 μm). Neither form bound heparan sulfate. These observations demonstrate that sulfated GAGs regulate matrilysin activation and its activity against specific substrates. PMID:19654318

The murine SP-C promoter directs type II cell-specific expression in transgenic mice.

PubMed

Glasser, Stephan W; Eszterhas, Susan K; Detmer, Emily A; Maxfield, Melissa D; Korfhagen, Thomas R

2005-04-01

Genomic DNA from the mouse pulmonary surfactant protein C (SP-C) gene was analyzed in transgenic mice to identify DNA essential for alveolar type II cell-specific expression. SP-C promoter constructs extending either 13 or 4.8 kb upstream of the transcription start site directed lung-specific expression of the bacterial chloramphenicol acetyl transferase (CAT) reporter gene. In situ hybridization analysis demonstrated alveolar cell-specific expression in the lungs of adult transgenic mice, and the pattern of 4.8 SP-C-CAT expression during development paralleled that of the endogenous SP-C gene. With the use of deletion constructs, lung-specific, low-level CAT activity was detected in tissue assays of SP-C-CAT transgenic mice retaining 318 bp of the promoter. In transient and stable cell transfection experiments, the 4.8-kb SP-C promoter was 90-fold more active as a stably integrated gene. These findings indicate that 1) the 4.8-kb SP-C promoter is sufficient to direct cell-specific and developmental expression, 2) an enhancer essential for lung-specific expression maps to the proximal 318-bp promoter, and 3) the activity of the 4.8-kb SP-C promoter construct is highly dependent on its chromatin environment.

Production of phytotoxic cationic α-helical antimicrobial peptides in plant cells using inducible promoters.

PubMed

Company, Nuri; Nadal, Anna; Ruiz, Cristina; Pla, Maria

2014-01-01

Synthetic linear antimicrobial peptides with cationic α-helical structures, such as BP100, have potent and specific activities against economically important plant pathogenic bacteria. They are also recognized as valuable therapeutics and preservatives. However, highly active BP100 derivatives are often phytotoxic when expressed at high levels as recombinant peptides in plants. Here we demonstrate that production of recombinant phytotoxic peptides in transgenic plants is possible by strictly limiting transgene expression to certain tissues and conditions, and specifically that minimization of this expression during transformation and regeneration of transgenic plants is essential to obtain viable plant biofactories. On the basis of whole-genome transcriptomic data available online, we identified the Os.hsp82 promoter that fulfilled this requirement and was highly induced in response to heat shock. Using this strategy, we generated transgenic rice lines producing moderate yields of severely phytotoxic BP100 derivatives on exposure to high temperature. In addition, a threshold for gene expression in selected tissues and stages was experimentally established, below which the corresponding promoters should be suitable for driving the expression of recombinant phytotoxic proteins in genetically modified plants. In view of the growing transcriptomics data available, this approach is of interest to assist promoter selection for specific purposes.

NiCoO2 flowers grown on the aligned-flakes coated Ni foam for application in hybrid energy storage

NASA Astrophysics Data System (ADS)

Xu, Xiaoyang; Zhao, Huilin; Zhou, JingKuo; Xue, Ruinan; Gao, Jianping

2016-10-01

Many NiCoO2 flowers with an average diameter of about 4 μm were grown on the NiCoO2 flakes coated Ni foam (denoted as NiCoO2/Ni foam) through a simple hydrothermal method and confirmed by scanning and transmission electron microscopies, X-ray diffraction and X-ray photoelectron spectrum measurements. The NiCoO2/Ni foam with high specific area and porosity was directly used as the working electrode without any binders. The measured specific capacitance of NiCoO2 grown on Ni foam is 756 F/g at 0.75 A/g using a three-electrode setup in 1 M KOH. Considering the high capacity of NiCoO2 and the good stability of rGO, the NiCoO2/Ni foam//rGO hybrid supercapacitor combining NiCoO2/Ni foam and rGO shows very good properties, such as high specific capacitance (82 F/g at 2 A/g based on the total mass of active materials), high energy density (25.7 Wh/kg at 1500 W/kg based on the total mass of active materials), good stability (about 90% capacitance retention after 2000-cycle at 100 mV/s), and low charge ion transfer resistance.

Production of Phytotoxic Cationic α-Helical Antimicrobial Peptides in Plant Cells Using Inducible Promoters

PubMed Central

Company, Nuri; Nadal, Anna; Ruiz, Cristina; Pla, Maria

2014-01-01

Synthetic linear antimicrobial peptides with cationic α-helical structures, such as BP100, have potent and specific activities against economically important plant pathogenic bacteria. They are also recognized as valuable therapeutics and preservatives. However, highly active BP100 derivatives are often phytotoxic when expressed at high levels as recombinant peptides in plants. Here we demonstrate that production of recombinant phytotoxic peptides in transgenic plants is possible by strictly limiting transgene expression to certain tissues and conditions, and specifically that minimization of this expression during transformation and regeneration of transgenic plants is essential to obtain viable plant biofactories. On the basis of whole-genome transcriptomic data available online, we identified the Os.hsp82 promoter that fulfilled this requirement and was highly induced in response to heat shock. Using this strategy, we generated transgenic rice lines producing moderate yields of severely phytotoxic BP100 derivatives on exposure to high temperature. In addition, a threshold for gene expression in selected tissues and stages was experimentally established, below which the corresponding promoters should be suitable for driving the expression of recombinant phytotoxic proteins in genetically modified plants. In view of the growing transcriptomics data available, this approach is of interest to assist promoter selection for specific purposes. PMID:25387106

EEG alpha synchronization is related to top-down processing in convergent and divergent thinking

PubMed Central

Benedek, Mathias; Bergner, Sabine; Könen, Tanja; Fink, Andreas; Neubauer, Aljoscha C.

2011-01-01

Synchronization of EEG alpha activity has been referred to as being indicative of cortical idling, but according to more recent evidence it has also been associated with active internal processing and creative thinking. The main objective of this study was to investigate to what extent EEG alpha synchronization is related to internal processing demands and to specific cognitive process involved in creative thinking. To this end, EEG was measured during a convergent and a divergent thinking task (i.e., creativity-related task) which once were processed involving low and once involving high internal processing demands. High internal processing demands were established by masking the stimulus (after encoding) and thus preventing further bottom-up processing. Frontal alpha synchronization was observed during convergent and divergent thinking only under exclusive top-down control (high internal processing demands), but not when bottom-up processing was allowed (low internal processing demands). We conclude that frontal alpha synchronization is related to top-down control rather than to specific creativity-related cognitive processes. Frontal alpha synchronization, which has been observed in a variety of different creativity tasks, thus may not reflect a brain state that is specific for creative cognition but can probably be attributed to high internal processing demands which are typically involved in creative thinking. PMID:21925520

Clear microstructure-performance relationships in Mn-containing perovskite and hexaaluminate compounds prepared by activated reactive synthesis.

PubMed

Laassiri, Said; Bion, Nicolas; Duprez, Daniel; Royer, Sébastien; Alamdari, Houshang

2014-03-07

Microstructural properties of mixed oxides play essential roles in their oxygen mobility and consequently in their catalytic performances. Two families of mixed oxides (perovskite and hexaaluminate) with different microstructural features, such as crystal size and specific surface area, were prepared using the activated reactive synthesis (ARS) method. It was shown that ARS is a flexible route to synthesize both mixed oxides with nano-scale crystal size and high specific surface area. Redox properties and oxygen mobility were found to be strongly affected by the material microstructure. Catalytic activities of hexaaluminate and perovskite materials for methane oxidation were discussed in the light of structural, redox and oxygen mobility properties.

mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency.

PubMed

Saada, Ann; Shaag, Avraham; Elpeleg, Orly

2003-05-01

Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to elucidate the mechanism of tissue specificity in the disease we have investigated the expression of the mitochondrial deoxynucleotide carrier, the mtDNA content and the activity of TK2 in mitochondria of various tissues. Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency.

Matrix metalloproteinase-9 (MMP-9) as an activator of nanosystems for targeted drug delivery in pancreatic cancer.

PubMed

Grünwald, Barbara; Vandooren, Jennifer; Locatelli, Erica; Fiten, Pierre; Opdenakker, Ghislain; Proost, Paul; Krüger, Achim; Lellouche, Jean Paul; Israel, Liron Limor; Shenkman, Louis; Comes Franchini, Mauro

2016-10-10

Specific cancer cell targeting is a pre-requisite for efficient drug delivery as well as for high-resolution imaging and still represents a major technical challenge. Tumor-associated enzyme-assisted targeting is a new concept that takes advantage of the presence of a specific activity in the tumor entity. MMP-9 is a protease found to be upregulated in virtually all malignant tumors. Consequently, we hypothesized that its presence can provide a de-shielding activity for targeted delivery of drugs by nanoparticles (NPs) in pancreatic cancer. Here, we describe synthesis and characterization of an optimized MMP-9-cleavable linker mediating specific removal of a PEG shield from a PLGA-b-PEG-based polymeric nanocarrier (Magh@PNPs-PEG-RegaCP-PEG) leading to specific uptake of the smaller PNPs with their cargo into cells. The specific MMP-9-cleavable linker was designed based on the degradation efficiency of peptides derived from the collagen type II sequence. MMP-9-dependent uptake of the Magh@PNPs-PEG-RegaCP-PEG was demonstrated in pancreatic cancer cells in vitro. Accumulation of the Magh@PNPs-PEG-RegaCP-PEG in pancreatic tissues in the clinically relevant KPC mouse model of pancreatic cancer, as a proof-of-concept, was tumor-specific and MMP-9-dependent, indicating that MMP-9 has a strong potential as a specific mediator of PNP de-shielding for tumor-specific uptake. Pre-treatment of mice with Magh@PNPs-PEG-RegaCP-PEG led to reduction of liver metastasis and drastically decreased average colony size. In conclusion, the increased tumor-specific presence and activity of MMP-9 can be exploited to deliver an MMP-9-activatable NP to pancreatic tumors specifically, effectively, and safely. Copyright © 2016 Elsevier B.V. All rights reserved.

Extensive peptide and natural protein substrate screens reveal that mouse caspase-11 has much narrower substrate specificity than caspase-1.

PubMed

Ramirez, Monica L Gonzalez; Poreba, Marcin; Snipas, Scott J; Groborz, Katarzyna; Drag, Marcin; Salvesen, Guy S

2018-05-04

Inflammatory cell death, or pyroptosis, is triggered by pathogenic infections or events. It is executed by caspase-1 (in the canonical pyroptosis pathway) or caspase-11 (noncanonical pathway), each via production of a cell-lytic domain from the pyroptosis effector protein gasdermin D through specific and limited proteolysis. Pyroptosis is accompanied by the release of inflammatory mediators, including the proteolytically processed forms of interleukin-1β (IL-1β) and IL-18. Given the similar inflammatory outcomes of the canonical and noncanonical pyroptosis pathways, we hypothesized that caspase-1 and -11 should have very similar activities and substrate specificities. To test this hypothesis, we purified recombinant murine caspases and analyzed their primary specificities by massive hybrid combinatorial substrate library (HyCoSuL) screens. We correlated the substrate preferences of each caspase with their activities on the recombinant natural substrates IL-1β, IL-18, and gasdermin D. Although we identified highly selective and robust peptidyl substrates for caspase-1, we were unable to do so for caspase-11, because caspase-1 cleaved even the best caspase-11 substrates equally well. Caspase-1 rapidly processed pro-IL-1β and -18, but caspase-11 processed these two pro-ILs extremely poorly. However, both caspase-1 and -11 efficiently produced the cell-lytic domain from the gasdermin D precursor. We hypothesize that caspase-11 may have evolved a specific exosite to selectively engage pyroptosis without directly activating pro-IL-1β or -18. In summary, comparing the activities of caspase-1 and -11 in HyCoSuL screens and with three endogenous protein substrates, we conclude that caspase-11 has highly restricted substrate specificity, preferring gasdermin D over all other substrates examined. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation

PubMed Central

Simion, Viorel; Constantinescu, Cristina Ana; Stan, Daniela; Deleanu, Mariana; Tucureanu, Monica Madalina; Butoi, Elena; Manduteanu, Ileana; Simionescu, Maya

2016-01-01

Inflammation is a common process associated with numerous vascular pathologies. We hypothesized that targeting the inflamed endothelium by coupling a peptide with high affinity for P-selectin to the surface of dexamethasone-loaded lipid nanoemulsions will highly increase their specific binding to activated endothelial cells (EC) and reduce the cell activation. We developed and characterized dexamethasone-loaded lipid nanoemulsions directed towards P-selectin (PLN-Dex) and monitored their anti-inflammatory effects in vitro using cultured EC (EA.hy926 cells) and in vivo using a mouse model of acute inflammation [lipopolysaccharides (LPS) intravenously administered in C57BL/6 mice]. We found that PLN-Dex bound specifically to the surface of activated EC are efficiently internalized by EC and reduced the expression of proinflammatory genes, thus preventing the monocyte adhesion and transmigration to/through activated EC. Given intravenously in mice with acute inflammation, PLN-Dex accumulated at a significant high level in the lungs (compared to nontargeted nanoemulsions) and significantly reduced mRNA expression level of key proinflammatory cytokines such as IL-1β, IL-6, and MCP-1. In conclusion, the newly developed nanoformulation, PLN-Dex, is functional in vitro and in vivo, reducing selectively the endothelium activation and the consequent monocyte infiltration and diminishing significantly the lungs' inflammation, in a mouse model of acute inflammation. PMID:27703301

Inhibition of Cell Wall-Associated Enzymes in Vitro and in Vivo with Sugar Analogs

PubMed Central

Nagahashi, Gerald; Tu, Shu-I; Fleet, George; Namgoong, Sun K.

1990-01-01

Sugar analogs were used to study the inhibition of cell wall-associated glycosidases in vitro and in vivo. For in vitro characterization, cell walls were highly purified from corn (Zea mays L.) root cortical cells and methods were developed to assay enzyme activity in situ. Inhibitor dependence curves, mode of inhibition, and specificity were determined for three sugar analogs. At low concentrations of castanospermine (CAS), 2-acetamido-1,5-imino-1,2,5-trideoxy-d-glucitol, and swainsonine, these inhibitors showed competitive inhibition kinetics with β-glucosidase, β-GIcNAcase, and α-mannosidase, respectively. Swainsonine specifically inhibited α-mannosidase activity, and 2-acetamido-1,5-imino-1,2,5-trideoxy-d-glucitol specifically inhibited β-N-acetyl-hexosamindase activity. However, CAS inhibited a broad spectrum of cell wall-associated enzymes. When the sugar analogs were applied to 2 day old corn seedlings, only CAS caused considerable changes in root growth and development. To ensure that the concentration of inhibitors used in vitro also inhibited enzyme activity in vivo, an in vivo method for measuring cell wall-associated activity was devised. PMID:16667291

90Sr in teeth of cattle abandoned in evacuation zone: Record of pollution from the Fukushima-Daiichi Nuclear Power Plant accident

NASA Astrophysics Data System (ADS)

Koarai, Kazuma; Kino, Yasushi; Takahashi, Atsushi; Suzuki, Toshihiko; Shimizu, Yoshinaka; Chiba, Mirei; Osaka, Ken; Sasaki, Keiichi; Fukuda, Tomokazu; Isogai, Emiko; Yamashiro, Hideaki; Oka, Toshitaka; Sekine, Tsutomu; Fukumoto, Manabu; Shinoda, Hisashi

2016-04-01

Here we determined the 90Sr concentrations in the teeth of cattle abandoned in the evacuation area of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident. 90Sr activity concentrations in the teeth varied from 6-831 mBq (g Ca)-1 and exhibited a positive relationship with the degree of radioactive contamination that the cattle experienced. Even within an individual animal, the specific activity of 90Sr (Bq (g Sr)-1) varied depending on the development stage of the teeth during the FNPP accident: teeth that were early in development exhibited high 90Sr specific activities, while teeth that were late in development exhibited low specific activities. These findings demonstrate that 90Sr is incorporated into the teeth during tooth development; thus, tooth 90Sr activity concentrations reflect environmental 90Sr levels during tooth formation. Assessment of 90Sr in teeth could provide useful information about internal exposure to 90Sr radiation and allow for the measurement of time-course changes in the degree of environmental 90Sr pollution.

An efficient ribitol-specific dehydrogenase from Enterobacter aerogenes.

PubMed

Singh, Ranjitha; Singh, Raushan; Kim, In-Won; Sigdel, Sujan; Kalia, Vipin C; Kang, Yun Chan; Lee, Jung-Kul

2015-05-01

An NAD(+)-dependent ribitol dehydrogenase from Enterobacter aerogenes KCTC 2190 (EaRDH) was cloned and successfully expressed in Escherichia coli. The complete 729-bp gene was amplified, cloned, expressed, and subsequently purified in an active soluble form using nickel affinity chromatography. The enzyme had an optimal pH and temperature of 11.0 and 45°C, respectively. Among various polyols, EaRDH exhibited activity only toward ribitol, with Km, Vmax, and kcat/Km values of 10.3mM, 185Umg(-1), and 30.9s(-1)mM(-1), respectively. The enzyme showed strong preference for NAD(+) and displayed no detectable activity with NADP(+). Homology modeling and sequence analysis of EaRDH, along with its biochemical properties, confirmed that EaRDH belongs to the family of NAD(+)-dependent ribitol dehydrogenases, a member of short-chain dehydrogenase/reductase (SCOR) family. EaRDH showed the highest activity and unique substrate specificity among all known RDHs. Homology modeling and docking analysis shed light on the molecular basis of its unusually high activity and substrate specificity. Copyright © 2015 Elsevier Inc. All rights reserved.

(90)Sr in teeth of cattle abandoned in evacuation zone: Record of pollution from the Fukushima-Daiichi Nuclear Power Plant accident.

PubMed

Koarai, Kazuma; Kino, Yasushi; Takahashi, Atsushi; Suzuki, Toshihiko; Shimizu, Yoshinaka; Chiba, Mirei; Osaka, Ken; Sasaki, Keiichi; Fukuda, Tomokazu; Isogai, Emiko; Yamashiro, Hideaki; Oka, Toshitaka; Sekine, Tsutomu; Fukumoto, Manabu; Shinoda, Hisashi

2016-04-05

Here we determined the (90)Sr concentrations in the teeth of cattle abandoned in the evacuation area of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident. (90)Sr activity concentrations in the teeth varied from 6-831 mBq (g Ca)(-1) and exhibited a positive relationship with the degree of radioactive contamination that the cattle experienced. Even within an individual animal, the specific activity of (90)Sr (Bq (g Sr)(-1)) varied depending on the development stage of the teeth during the FNPP accident: teeth that were early in development exhibited high (90)Sr specific activities, while teeth that were late in development exhibited low specific activities. These findings demonstrate that (90)Sr is incorporated into the teeth during tooth development; thus, tooth (90)Sr activity concentrations reflect environmental (90)Sr levels during tooth formation. Assessment of (90)Sr in teeth could provide useful information about internal exposure to (90)Sr radiation and allow for the measurement of time-course changes in the degree of environmental (90)Sr pollution.

90Sr in teeth of cattle abandoned in evacuation zone: Record of pollution from the Fukushima-Daiichi Nuclear Power Plant accident

PubMed Central

Koarai, Kazuma; Kino, Yasushi; Takahashi, Atsushi; Suzuki, Toshihiko; Shimizu, Yoshinaka; Chiba, Mirei; Osaka, Ken; Sasaki, Keiichi; Fukuda, Tomokazu; Isogai, Emiko; Yamashiro, Hideaki; Oka, Toshitaka; Sekine, Tsutomu; Fukumoto, Manabu; Shinoda, Hisashi

2016-01-01

Here we determined the 90Sr concentrations in the teeth of cattle abandoned in the evacuation area of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident. 90Sr activity concentrations in the teeth varied from 6–831 mBq (g Ca)−1 and exhibited a positive relationship with the degree of radioactive contamination that the cattle experienced. Even within an individual animal, the specific activity of 90Sr (Bq (g Sr)−1) varied depending on the development stage of the teeth during the FNPP accident: teeth that were early in development exhibited high 90Sr specific activities, while teeth that were late in development exhibited low specific activities. These findings demonstrate that 90Sr is incorporated into the teeth during tooth development; thus, tooth 90Sr activity concentrations reflect environmental 90Sr levels during tooth formation. Assessment of 90Sr in teeth could provide useful information about internal exposure to 90Sr radiation and allow for the measurement of time-course changes in the degree of environmental 90Sr pollution. PMID:27045764

[Substrate specificities of bile salt hydrolase 1 and its mutants from Lactobacillus salivarius].

PubMed

Bi, Jie; Fang, Fang; Qiu, Yuying; Yang, Qingli; Chen, Jian

2014-03-01

In order to analyze the correlation between critical residues in the catalytic centre of BSH and the enzyme substrate specificity, seven mutants of Lactobacillus salivarius bile salt hydrolase (BSH1) were constructed by using the Escherichia coli pET-20b(+) gene expression system, rational design and site-directed mutagenesis. These BSH1 mutants exhibited different hydrolytic activities against various conjugated bile salts through substrate specificities comparison. Among the residues being tested, Cys2 and Thr264 were deduced as key sites for BSH1 to catalyze taurocholic acid and glycocholic acid, respectively. Moreover, Cys2 and Thr264 were important for keeping the catalytic activity of BSH1. The high conservative Cys2 was not the only active site, other mutant amino acid sites were possibly involved in substrate binding. These mutant residues might influence the space and shape of the substrate-binding pockets or the channel size for substrate passing through and entering active site of BSH1, thus, the hydrolytic activity of BSH1 was changed to different conjugated bile salt.

Imaging and targeted therapy of pancreatic ductal adenocarcinoma using the theranostic sodium iodide symporter (NIS) gene

PubMed Central

Trajkovic-Arsic, Marija; Klutz, Kathrin; Braren, Rickmer; Schwaiger, Markus; Nelson, Peter J.; Ogris, Manfred; Wagner, Ernst; Siveke, Jens T.; Spitzweg, Christine

2017-01-01

The theranostic sodium iodide symporter (NIS) gene allows detailed molecular imaging of transgene expression and application of therapeutic radionuclides. As a crucial step towards clinical application, we investigated tumor specificity and transfection efficiency of epidermal growth factor receptor (EGFR)-targeted polyplexes as systemic NIS gene delivery vehicles in an advanced genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) that closely reflects human disease. PDAC was induced in mice by pancreas-specific activation of constitutively active KrasG12D and deletion of Trp53. We used tumor-targeted polyplexes (LPEI-PEG-GE11/NIS) based on linear polyethylenimine, shielded by polyethylene glycol and coupled with the EGFR-specific peptide ligand GE11, to target a NIS-expressing plasmid to high EGFR-expressing PDAC. In vitro iodide uptake studies in cell explants from murine EGFR-positive and EGFR-ablated PDAC lesions demonstrated high transfection efficiency and EGFR-specificity of LPEI-PEG-GE11/NIS. In vivo 123I gamma camera imaging and three-dimensional high-resolution 124I PET showed significant tumor-specific accumulation of radioiodide after systemic LPEI-PEG-GE11/NIS injection. Administration of 131I in LPEI-PEG-GE11/NIS-treated mice resulted in significantly reduced tumor growth compared to controls as determined by magnetic resonance imaging, though survival was not significantly prolonged. This study opens the exciting prospect of NIS-mediated radionuclide imaging and therapy of PDAC after systemic non-viral NIS gene delivery. PMID:28380420

Developing a User Oriented Design Methodology for Learning Activities Using Boundary Objects

ERIC Educational Resources Information Center

Fragou, ?lga; Kameas, Achilles

2013-01-01

International Standards in High and Open and Distance Education are used for developing Open Educational Resources (OERs). Current issues in e-learning community are the specification of learning chunks and the definition of describing designs for different units of learning (activities, units, courses) in a generic though expandable format.…

Promoting Readiness to Practice: Which Learning Activities Promote Competence and Professional Identity for Student Social Workers during Practice Learning?

ERIC Educational Resources Information Center

Roulston, Audrey; Cleak, Helen; Vreugdenhil, Anthea

2018-01-01

Practice learning is integral to the curriculum for qualifying social work students. Accreditation standards require regular student supervision and exposure to specific learning activities. Most agencies offer high-quality placements, but organizational cutbacks may affect supervision and restrict the development of competence and professional…

Probing High School Physics Students' Views and Concerns about Learning Activities

ERIC Educational Resources Information Center

Langley, Dorothy; Eylon, Bat-Sheva

2006-01-01

The current study is framed within an ongoing effort of probing students' attitudes and expectations about knowing and learning physics, which has driven several investigations during the past decade. The questionnaire we developed focuses on physics students' views regarding a variety of specific learning activities, which are presented by title…

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

ERIC Educational Resources Information Center

Levy, Corey

2010-01-01

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

Participation in Sports-Related Extracurricular Activities: A Strategy That Enhances School Engagement

ERIC Educational Resources Information Center

St-Amand, Jerome; Girard, Stéphanie; Hiroux, Marie-Hélène; Smith, Jonathan

2017-01-01

This article outlines a strategy that we, as high school teachers, used in the academic year 2012-2013 to improve a student's school engagement. Extracurricular activities such as sports have proven useful (among other strategies) to counter school disengagement, specifically in enhancing positive social relations among the teachers and students…

The Instrument for the Observation of Teaching Activities (IOTA) and Alternative Approaches to Remediation of Teacher Weaknesses.

ERIC Educational Resources Information Center

Richardson, Donald C.; Hatley, Richard V.

1980-01-01

Comparing the effectiveness of different strategies for remediating teacher weaknesses, as measured by the Instrument for Observation of Teaching Activities (IOTA), 99 elementary and junior high school teachers were observed. The study revealed that combining IOTA feedback with structured inservice workshops focusing on narrow specific weaknesses…

Relations among water levels, specific conductance, and depths of bedrock fractures in four road-salt-contaminated wells in Maine, 2007–9

USGS Publications Warehouse

Schalk, Charles W.; Stasulis, Nicholas W.

2012-01-01

Data on groundwater-level, specific conductance (a surrogate for chloride), and temperature were collected continuously from 2007 through 2009 at four bedrock wells known to be affected by road salts in an effort to determine the effects of road salting and fractures in bedrock that intersect the well at a depth below the casing on the presence of chloride in groundwater. Dissolved-oxygen data collected periodically also were used to make inferences about the interaction of fractures and groundwater flow. Borehole geophysical tools were used to determine the depths of fractures in each well that were actively contributing flow to the well, under both static and pumped conditions; sample- and measurement-depths were selected to correspond to the depths of these active fractures. Samples of water from the wells, collected at depths corresponding to active bedrock fractures, were analyzed for chloride concentration and specific conductance; from these analyses, a linear relation between chloride concentration and specific conductance was established, and continuous and periodic measurements of specific conductance were assumed to represent chloride concentration of the well water at the depth of measurement. To varying degrees, specific conductance increased in at least two of the wells during winter and spring thaws; the shallowest well, which also was closest to the road receiving salt treatment during the winter, exhibited the largest changes in specific conductance during thaws. Recharge events during summer months, long after application of road salt had ceased for the year, also produced increases in specific conductance in some of the wells, indicating that chloride which had accumulated or sequestered in the overburden was transported to the wells throughout the year. Geophysical data and periodic profiles of water quality along the length of each well’s borehole indicated that the greatest changes in water quality were associated with active fractures; in one case, high concentration of dissolved oxygen at the bottom of the well indicated the presence of a highly transmissive fracture that was in good connection with a surficial feature (stream or atmosphere). Data indicated that fractures have a substantial influence on the transport of chlorides to the subsurface; that elevated specific conductance occurred throughout the year, not just when road salts were applied; and that chloride contamination, as indicated by elevated specific conductance, may persist for years.

Origin and Function of Circulating Plasmablasts during Acute Viral Infections.

PubMed

Fink, Katja

2012-01-01

Activated B cells proliferate and differentiate into antibody-producing cells, long-lived plasma cells, and memory B cells after immunization or infection. Repeated encounter of the same antigen triggers the rapid re-activation of pre-existing specific memory B cells, which then potentially enter new germinal center reactions and differentiate into short-lived plasmablasts or remain in the system as memory B cells. Short-lived class-switched IgG and IgA plasmablasts appear in the circulation transiently and the frequency of these cells can be remarkably high. The specificities and affinities of single plasmablasts in humans have been reported for several viral infections, so far most extensively for influenza and HIV. In general, the immunoglobulin variable regions of plasmablasts are highly mutated and diverse, suggesting that plasmablasts are derived from memory B cells, yet it is unclear which memory B cell subsets are activated and whether activated memory B cells adapt or mature before differentiation. This review summarizes what is known about the phenotype and the origin of human plasmablasts in the context of viral infections and whether these cells can be predictors of long-lived immunity.

Enzyme-Mediated Individual Nanoparticle Release Assay

PubMed Central

Glass, James R.; Dickerson, Janet C.; Schultz, David A.

2007-01-01

Numerous methods have been developed to measure the presence of macromolecular species in a sample, however methods that detect functional activity, or modulators of that activity are more limited. To address this limitation, an approach was developed that utilizes the optical detection of nanoparticles as a measure of enzyme activity. Nanoparticles are increasingly being used as biological labels in static binding assays; here we describe their use in a release assay format where the enzyme-mediated liberation of individual nanoparticles from a surface is measured. A double stranded fragment of DNA is used as the initial tether to bind the nanoparticles to a solid surface. The nanoparticle spatial distribution and number are determined using dark-field optical microscopy and digital image capture. Site specific cleavage of the DNA tether results in nanoparticle release. The methodology and validation of this approach for measuring enzyme-mediated, individual DNA cleavage events, rapidly, with high specificity, and in real-time is described. This approach was used to detect and discriminate between non-methylated and methylated DNA, and demonstrates a novel platform for high-throughput screening of modulators of enzyme activity. PMID:16620746

Actinobacteria possessing antimicrobial and antioxidant activities isolated from the pollen of scots pine (Pinus sylvestris) grown on the Baikal shore.

PubMed

Axenov-Gribanov, Denis V; Voytsekhovskaya, Irina V; Rebets, Yuriy V; Tokovenko, Bogdan T; Penzina, Tatyana A; Gornostay, Tatyana G; Adelshin, Renat V; Protasov, Eugenii S; Luzhetskyy, Andriy N; Timofeyev, Maxim A

2016-10-01

Isolated ecosystems existing under specific environmental conditions have been shown to be promising sources of new strains of actinobacteria. The taiga forest of Baikal Siberia has not been well studied, and its actinobacterial population remains uncharacterized. The proximity between the huge water mass of Lake Baikal and high mountain ranges influences the structure and diversity of the plant world in Siberia. Here, we report the isolation of eighteen actinobacterial strains from male cones of Scots pine trees (Pinus sylvestris) growing on the shore of the ancient Lake Baikal in Siberia. In addition to more common representative strains of Streptomyces, several species belonging to the genera Rhodococcus, Amycolatopsis, and Micromonospora were isolated. All isolated strains exhibited antibacterial and antifungal activities. We identified several strains that inhibited the growth of the pathogen Candida albicans but did not hinder the growth of Saccharomyces cerevisiae. Several isolates were active against Gram-positive and Gram-negative bacteria. The high proportion of biologically active strains producing antibacterial and specific antifungal compounds may reflect their role in protecting pollen against phytopathogens.

Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism

PubMed Central

Dahms, Sven O.; Arciniega, Marcelino; Steinmetzer, Torsten; Huber, Robert; Than, Manuel E.

2016-01-01

Proprotein convertases (PCs) are highly specific proteases required for the proteolytic modification of many secreted proteins. An unbalanced activity of these enzymes is connected to pathologies like cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Novel protein crystallographic structures of the prototypical PC family member furin in different functional states were determined to 1.8–2.0 Å. These, together with biochemical data and modeling by molecular dynamics calculations, suggest essential elements underlying its unusually high substrate specificity. Furin shows a complex activation mechanism and exists in at least four defined states: (i) the “off state,” incompatible with substrate binding as seen in the unliganded enzyme; (ii) the active “on state” seen in inhibitor-bound furin; and the respective (iii) calcium-free and (iv) calcium-bound forms. The transition from the off to the on state is triggered by ligand binding at subsites S1 to S4 and appears to underlie the preferential recognition of the four-residue sequence motif of furin. The molecular dynamics simulations of the four structural states reflect the experimental observations in general and provide approximations of the respective stabilities. Ligation by calcium at the PC-specific binding site II influences the active-site geometry and determines the rotamer state of the oxyanion hole-forming Asn295, and thus adds a second level of the activity modulation of furin. The described crystal forms and the observations of different defined functional states may foster the development of new tools and strategies for pharmacological intervention targeting furin. PMID:27647913

Improving practice with integration of patient directed activity during inpatient rehabilitation.

PubMed

Trammell, Molly; Kapoor, Priyanka; Swank, Chad; Driver, Simon

2017-01-01

Early initiation of rehabilitation following stroke promotes better long-term outcomes than delayed onset, emphasizing the importance of inpatient therapy. However, literature indicates that following stroke individuals in inpatient rehabilitation spend the majority of their day in their bedroom and inactive. Consequently, since amount of functional activity is posited to relate to outcomes, the current rehabilitation model needs to be challenged with innovative solutions to maximize recovery. In an attempt to promote greater activity and higher doses of therapy during inpatient rehabilitation, we implemented the "Patient Directed Activity Program" to facilitate specific movement and improve outcomes for patients post stroke. Our interdisciplinary activity program was conceptualized on a theoretical model for stroke recovery and principles of experience-dependent neural plasticity. The "Patient Directed Activity Program" includes distinct activity stations designed to increase repetition, stimulation, attention, and activity of the affected upper extremities, lower extremities, and trunk. Each task-specific activity was easily graded to achieve moderate- to high-intensity. The activity program prescribed individuals up to three additional 30-minute bouts of activities daily that were to be completed independently, and in addition to standard of care. Clinical application: After implementing this program in our facility for one year as a quality improvement project, the intervention has been delivered as an Institutional Review Board approved randomized controlled trial (Clinical Trial #NCT02446197). Challenges with people and facilities have been overcome, resulting in a feasible program that can be delivered in an inpatient setting. High satisfaction has been reported by patients and clinicians.

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

PubMed

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

2016-07-01

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

Standardized methods for the production of high specific-activity zirconium-89

PubMed Central

Holland, Jason P.; Sheh, Yiauchung; Lewis, Jason S.

2009-01-01

Zirconium-89 is an attractive metallo-radionuclide for use in immunoPET due to the favorable decay characteristics. Standardized methods for the routine production and isolation of high purity and high specific-activity 89Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52 ± 0.11 mCi/μA·h at a proton beam energy of 15 MeV and current of 15 μA using a solid, commercially available 89Y-foil target (0.1 mm, 100% natural abundance). 89Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [89Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of 89Zr was found to be in the range 5.28 – 13.43 mCi/μg (470 – 1195 Ci/mmol) of zirconium. New methods for the facile production of [89Zr]Zr-chloride are reported. Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) gave 100% radiochemical yields in <15 min. at room temperature and in vitro stability measurements confirmed that [89Zr]Zr-DFO is stable with respect to ligand dissociation in human serum for >7 days. Small-animal PET imaging studies have demonstrated that free 89Zr(IV) ions administered as [89Zr]Zr-chloride accumulate in the liver whilst [89Zr]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immunoPET imaging of 89Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of 89Zr in both basic science and clinical investigations. PMID:19720285

Production of no-carrier-added 64Cu from zinc metal irradiated under boron shielding.

PubMed

Zinn, K R; Chaudhuri, T R; Cheng, T P; Morris, J S; Meyer, W A

1994-02-01

Positron emission tomography offers advantages for radioimmunodiagnosis of cancer but requires radionuclides of appropriate half-life that have high specific activity and high radio-purity. This work was designed to develop a viable method to produce and purify 64Cu, which has high specific activity, for positron emission tomography. 64Cu was produced at the University of Missouri Research Reactor by the nuclear reaction, 64Zn(n,p)64Cu. Highly pure zinc metal (99.9999%) was irradiated in a specially designed boron nitrite lined container, which minimized thermal neutron reactions during irradiation. A new two-step procedure was developed to chemically separate the no-carrier-added 64Cu from the zinc metal target. 64Cu recovery for 24 runs averaged 0.393 (+/- 0.007) mCi per milligram of zinc irradiated. The boron-lined irradiation container reduced unwanted zinc radionuclides 14.3-fold. Zinc radionuclides and non-radioactive zinc were separated successfully from the 64Cu. The new separation technique was fast (2 hours total time) and highly efficient for removing the zinc. The zinc separation factor for this technique averaged 8.5 x 10(-8), indicating less than 0.0000085% of the zinc remained after separation. Thus far, the highest 64Cu specific activity at end of irradiation was 683 Ci/mg Cu, with an average of 512 Ci/mg Cu for the last six analyzed runs. The boron-lined irradiation container has sufficient capacity for 75-fold larger-sized zinc targets (up to 45 g). The new separation technique was excellent for separating 64Cu, which appears to be a radionuclide with great potential for positron emission tomography.

Biasing the brain's attentional set: I. cue driven deployments of intersensory selective attention.

PubMed

Foxe, John J; Simpson, Gregory V; Ahlfors, Seppo P; Saron, Clifford D

2005-10-01

Brain activity associated with directing attention to one of two possible sensory modalities was examined using high-density mapping of human event-related potentials. The deployment of selective attention was based on visually presented symbolic cue-words instructing subjects on a trial-by-trial basis, which sensory modality to attend. We measured the spatio-temporal pattern of activation in the approximately 1 second period between the cue-instruction and a subsequent compound auditory-visual imperative stimulus. This allowed us to assess the flow of processing across brain regions involved in deploying and sustaining inter-sensory selective attention, prior to the actual selective processing of the compound audio-visual target stimulus. Activity over frontal and parietal areas showed sensory specific increases in activation during the early part of the anticipatory period (~230 ms), probably representing the activation of fronto-parietal attentional deployment systems for top-down control of attention. In the later period preceding the arrival of the "to-be-attended" stimulus, sustained differential activity was seen over fronto-central regions and parieto-occipital regions, suggesting the maintenance of sensory-specific biased attentional states that would allow for subsequent selective processing. Although there was clear sensory biasing in this late sustained period, it was also clear that both sensory systems were being prepared during the cue-target period. These late sensory-specific biasing effects were also accompanied by sustained activations over frontal cortices that also showed both common and sensory specific activation patterns, suggesting that maintenance of the biased state includes top-down inputs from generators in frontal cortices, some of which are sensory-specific regions. These data support extensive interactions between sensory, parietal and frontal regions during processing of cue information, deployment of attention, and maintenance of the focus of attention in anticipation of impending attentionally relevant input.

Characterization and use of a rabbit-anti-mouse VPAC1 antibody by flow cytometry

PubMed Central

Hermann, Rebecca J.; Van der Steen, Travis; Vomhof-DeKrey, Emilie E.; Benton, Keith D.; Failing, Jarrett J.; Haring, Jodie S.; Dorsam, Glenn P.

2011-01-01

Vasoactive intestinal peptide receptor – 1 signaling in lymphocytes has been shown to regulate chemotaxis, proliferation, apoptosis and differentiation. During T cell activation, VPAC1 mRNA is downregulated, but the effect on its protein levels is less clear. A small number of studies have reported measurement of human VPAC1 by flow cytometry, but murine VPAC1 reagents are unavailable. Therefore, we set out to generate a reliable and highly specific α-mouse VPAC1 polyclonal antibody for use with flow cytometry. After successfully generating a rabbit α-VPAC1 polyclonal antibody (α-mVPAC1 pAb), we characterized its cross-reactivity and showed that it does not recognize other family receptors (mouse VPAC2 and PAC1, human VPAC1, VPAC2 and PAC1) by flow cytometry. Partial purification of the rabbit α-VPAC1 sera increased the specific-activity of the α-mVPAC1 pAb by 20-fold, and immunofluorescence microscopy (IF) confirmed a plasma membrane subcellular localization for mouse VPAC1 protein. To test the usefulness of this specific α-mVPAC1 pAb, we showed that primary, resting mouse T cells express detectable levels of VPAC1 protein, with little detectable signal from activated T cells, or CD19 B cells. These data support our previously published data showing a downregulation of VPAC1 mRNA during T cell activation. Collectively, we have established a well-characterized, and highly species specific α-mVPAC1 pAb for VPAC1 surface measurement by IF and flow cytometry. PMID:22079255

Evaluation of a high-resolution patient-specific model of the electrically stimulated cochlea

NASA Astrophysics Data System (ADS)

Cakir, Ahmet; Dwyer, Robert T.; Noble, Jack H.

2017-03-01

Cochlear implants (CIs) are considered standard treatment for patients who experience sensorineural hearing loss. Although these devices have been remarkably successful at restoring hearing, it is rare to achieve natural fidelity, and many patients experience poor outcomes. Our group has developed the first image-guided CI programming (IGCIP) technique where the positions of the electrodes are found in CT images and used to estimate neural activation patterns, which is unique information that audiologists can use to define patient-specific processor settings. In our current system, neural activation is estimated using only the distance from each electrode to the neural activation sites. This approach might be less accurate than using a high-resolution electro-anatomical model (EAM) of the electrically stimulated cochlea to perform physics-based estimation of neural activation. In this work, we propose a patientcustomized EAM approach where the EAM is spatially and electrically adapted to a patient-specific configuration. Spatial adaptation is done through non-rigid registration of the model with the patient CT image. Electrical adaptation is done by adjusting tissue resistivity parameters so that the intra-cochlear voltage distributions predicted by the model best match those directly measured for the patient via their implant. We demonstrated our approach for N=7 patients. We found that our approach results in mean percent differences between direct and simulated measurements of voltage distributions of 11%. In addition, visual comparison shows the simulated and measured voltage distributions are qualitatively in good agreement. This represents a crucial step toward developing and validating the first in vivo patient-specific cochlea EAMs.

Simple, high-yield purification of xanthine oxidase from bovine milk.

PubMed

Ozer, N; Müftüoglu, M; Ataman, D; Ercan, A; Ogüs, I H

1999-05-13

Xanthine oxidase, a commercially important enzyme with a wide area of application, was extracted from fresh milk, without added preservatives, using toluene and heat. The short purification procedure, with high yield, consisted of extraction, ammonium sulfate fractionation, and DEAE-Sepharose (fast flow) column chromatography. Xanthine oxidase was eluted as a single activity peak from the column using a buffer gradient. The purification fold, specific activity and yield for the purified xanthine oxidase were 328, 10.161 U/mg and 69%, respectively. The enzyme was concentrated by ultrafiltration, although 31% of the activity was lost during concentration, no change in specific activity was observed. Activity and protein gave coincident staining bands on native polyacrylamide gels. The intensity and the number of bands were dependent on the oxidative state(s) of the enzyme; reduction by 2-mercaptoethanol decreased the intensity of the slow-moving bands and increased the intensity of the fastest-moving band. Following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), two major bands (molecular masses of 152 and 131 kDa) were observed, accounting for > or = 95% of xanthine oxidase. Native- and SDS-PAGE showed that the purified xanthine oxidase becomes a heterodimer due to endogenous proteases.

Dynamic Precursors of Flares in Active Region NOAA 10486

NASA Astrophysics Data System (ADS)

Korsós, M. B.; Gyenge, N.; Baranyi, T.; Ludmány, A.

2015-03-01

Four different methods are applied here to study the precursors of flare activity in the Active Region NOAA 10486. Two approaches track the temporal behaviour of suitably chosen features (one, the weighted hori- zontal gradient W G M , is the generalized form of the horizontal gradient of the magnetic field, G M ; the other is the sum of the horizontal gradient of the magnetic field, G S , for all sunspot pairs). W G M is a photospheric indicator, that is a proxy measure of magnetic non-potentiality of a specific area of the active region, i.e., it captures the temporal variation of the weighted horizontal gradient of magnetic flux summed up for the region where opposite magnetic polarities are highly mixed. The third one, referred to as the separateness parameter, S l- f , considers the overall morphology. Further, G S and S l- f are photospheric, newly defined quick-look indicators of the polarity mix of the entire active region. The fourth method is tracking the temporal variation of small X-ray flares, their times of succession and their energies observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager instrument. All approaches yield specific pre-cursory signatures for the imminence of flares.

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

PubMed Central

Scherer, Luciene Cardoso; Sperhacke, Rosa Dea; Jarczewski, Carla; Cafrune, Patrícia I; Minghelli, Simone; Ribeiro, Marta Osório; Mello, Fernanda CQ; Ruffino-Netto, Antonio; Rossetti, Maria LR; Kritski, Afrânio L

2007-01-01

Background Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of Mycobacterium tuberculosis (MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection. Methods To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB. Results In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%–78%) and specificity of 83% (CI 95%: 75%–89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%–84%) and specificity of 86% (CI 95%:78%–92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively. Conclusion PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital. PMID:18096069

Teacher and student perspectives on motivation within the high school science classroom

NASA Astrophysics Data System (ADS)

Pickens, Melanie Turnure

The purpose of this study was to investigate teacher and student perspectives on the motivation of high school science students and to explore specific motivational strategies used by teachers as they attempt to enhance student motivation. Four science teachers took part in an initial audio-taped interview, classroom observations with debriefing conversations, and a final audio-taped interview to discuss findings and allow member checking for data triangulation and interpretation. Participating teachers also took part in a final focus group interview. Student participants from each teacher's class were given a Likert style anonymous survey on their views about motivation and learning, motivation in science class, and specific motivational strategies that emerged in their current science class. This study focused on effective teaching strategies for motivation commonly used by the four teachers and on specific teaching strategies used by two of these four teachers in different tracks of science classes. The intent was to determine not only what strategies worked well for all types of science classes, but also what specific motivational approaches were being used in high and low tracked science classes and the similarities and differences between them. This approach provided insight into the differences in motivating tracked students, with the hope that other educators in specific tracks might use such pedagogies to improve motivation in their own science classrooms. Results from this study showed that science teachers effectively motivate their students in the following ways: Questioning students to engage them in the lesson, exhibiting enthusiasm in lesson presentations, promoting a non-threatening environment, incorporating hands-on activities to help learn the lesson concepts, using a variety of activities, believing that students can achieve, and building caring relationships in the classroom. Specific to the higher tracked classroom, effective motivational strategies included: Use of teacher enthusiasm, promoting a non-threatening class atmosphere, and connecting the adolescent world to science. In the lower tracked classroom, specific effective strategies were: Encouraging student-student dialogue, making lessons relevant using practical applications, building student self-confidence, and using hands-on inquiry activities. Teachers who incorporate such strategies into their classrooms regardless of the track will likely increase motivation and also enhance learning for all students.

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.

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

PubMed

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

2015-01-30

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

Protective antigens from El Tor vibrios

PubMed Central

Watanabe, Yoshikazu; Verwey, W. F.

1965-01-01

A biochemically and immunologically homogeneous antigenic fraction having the properties of a lipopolysaccharide has been isolated from the culture supernatant of an El Tor vibrio (Ogawa subtype). This antigen was very specifically protective for mice challenged with Ogawa strains of either El Tor vibrios or Vibrio cholerae. Rabbit antisera prepared against the antigen were passively protective for mice and highly vibriocidal but had little agglutinating activity. However, the antigen was able specifically to absorb agglutinins, as well as mouse-protective and vibriocidal antibody from serum prepared against whole bacterial cells. The specific protective activity of this lipopolysaccharide was much greater than that of vaccines made from whole bacterial cells, and its toxicity in animals was about equivalent to that of whole cells. The relationship of activity to toxicity therefore represented an improvement over the vaccines that were studied. ImagesFIG. 1FIG. 3FIG. 4FIG. 5 PMID:5294306

Drug conjugated nanoparticles activated by cancer cell specific mRNA.

PubMed

Gossai, Nathan P; Naumann, Jordan A; Li, Nan-Sheng; Zamora, Edward A; Gordon, David J; Piccirilli, Joseph A; Gordon, Peter M

2016-06-21

We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated.

The high surface energy of NiO {110} facets incorporated into TiO2 hollow microspheres by etching Ti plate for enhanced photocatalytic and photoelectrochemical activity

NASA Astrophysics Data System (ADS)

Li, Jian; Cui, Hongzhi; Song, Xiaojie; Wei, Na; Tian, Jian

2017-02-01

We present a rational design for the controllable synthesis of NiO/TiO2 hollow microspheres (NTHMs) with Ti plate via a one-pot template-free synthesis strategy. Specifically, to enhance the formation of hollow microspheres, part of the titanium source is provided by the Ti plate. The hollow spherical NiO/TiO2 particles possess unique microstructural characteristics, namely, a higher specific surface area (∼65.82 m2 g-1), a larger mesoporous structure (∼7.79 nm), and hierarchical nanoarchitectures connected with mesopores within the shell (monodispersed size of ∼1 μm and shell thickness of ∼80 nm). In addition, as a cocatalyst for improved catalytic activity, the incorporated NiO nanoparticles with exposed high surface energy {110} facets displayed an outstanding performance. It has been proven that this facile nanostructure possesses remarkably high photoelectrochemical and photocatalytic activities. The main mechanism for enhancement of photocatalytic activity is attributed to the construction of p-n junctions with an inner electric field between TiO2 and NiO, which can dramatically enhance the separation efficiency of the photogenerated electron-hole pairs. This strategy could be applied to fabricate mixed metal oxide hollow microspheres toward the photoelectrochemical catalysis.

CD8+ T Cell-Mediated Immunity during Trypanosoma cruzi Infection: A Path for Vaccine Development?

PubMed Central

dos Santos Virgilio, Fernando; Pontes, Camila; Dominguez, Mariana Ribeiro; Ersching, Jonatan; Rodrigues, Mauricio Martins; Vasconcelos, José Ronnie

2014-01-01

MHC-restricted CD8+ T cells are important during infection with the intracellular protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Experimental studies performed in the past 25 years have elucidated a number of features related to the immune response mediated by these T cells, which are important for establishing the parasite/host equilibrium leading to chronic infection. CD8+ T cells are specific for highly immunodominant antigens expressed by members of the trans-sialidase family. After infection, their activation is delayed, and the cells display a high proliferative activity associated with high apoptotic rates. Although they participate in parasite control and elimination, they are unable to clear the infection due to their low fitness, allowing the parasite to establish the chronic phase when these cells then play an active role in the induction of heart immunopathology. Vaccination with a number of subunit recombinant vaccines aimed at eliciting specific CD8+ T cells can reverse this path, thereby generating a productive immune response that will lead to the control of infection, reduction of symptoms, and reduction of disease transmission. Due to these attributes, activation of CD8+ T lymphocytes may constitute a path for the development of a veterinarian or human vaccine. PMID:25104879

Natural radioactive contaminants in solder

NASA Astrophysics Data System (ADS)

Bunzl, K.; Kracke, W.

1985-07-01

Comparatively high surface count rates for alpha- and beta-radiation were observed for several solders. They were identified as 210Pb and 210Po. The corresponding specific activities in solder were determined.

Business Studies 9. Junior High School. Teacher Resource Manual.

ERIC Educational Resources Information Center

Alberta Dept. of Education, Edmonton. Curriculum Branch.

This manual provides learning strategies and activities, evaluation instruments, and learning resources for use by junior high school business education teachers. It is correlated with the Alberta business education curriculum. The manual begins with an overview of the course rationale and philosophy and general and specific learner expectations.…

Mtb-specific CD27low CD4 T cells as markers of lung tissue destruction during pulmonary tuberculosis in humans.

PubMed

Nikitina, Irina Yu; Kondratuk, Natalya A; Kosmiadi, George A; Amansahedov, Rasul B; Vasilyeva, Irina A; Ganusov, Vitaly V; Lyadova, Irina V

2012-01-01

Effector CD4 T cells represent a key component of the host's anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection. The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27(low) cells within a population of Mtb- specific CD4 T lymphocytes ("CD27(low)IFN-γ(+)" cells). The percentages of CD27(low)IFN-γ+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27(low)IFN-γ(+) cells were uniformly high in the lungs (>76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27(low)IFN-γ(+) cells in blood was lung destruction (r = 0.65, p = 2.7 × 10(-7)). A cutoff of 47% of CD27(low)IFN-γ(+) cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27(low)IFN-γ(+)cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01). Highly differentiated CD27(low) Mtb-specific (CD27(low)IFN-γ(+)) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27(low)IFN-γ(+) cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell differentiation during TB; evaluation of CD27(low)IFN-γ(+) cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy.

High porous bio-nanocarbons prepared by carbonization and NaOH activation of polysaccharides for electrode material of EDLC

NASA Astrophysics Data System (ADS)

Takeuchi, Kenji; Fujishige, Masatsugu; Ishida, Nobuaki; Kunieda, Yoshihiro; Kato, Yosuke; Tanaka, Yusuke; Ochi, Toshiyuki; Shirotori, Hisashi; Uzuhashi, Yuji; Ito, Suguru; Oshida, Kyo-ichi; Endo, Morinobu

2018-07-01

Carbonization and post-activation of polysaccharides (utilized as food residue) created new bio-nanocarbons for the electrode of electric double layer capacitors (EDLC). Large specific capacitance (46.1 F/g, 26.4 F/cm3) and high rate performance was confirmed under optimized conditions of carbonization temperature (600 °C) and supplied amount of sodium hydroxide in NaOH-activation process (250 wt %). The capacitance and rate performance were larger than the reported values, 42.9 F/g, 19.7 F/cm3 of currently used activated carbon MSP-20. The feature that NaOH is usable as the activation agent, instead of KOH, is advantageous for reducing the cost of EDLC.

Capacity of novelty-induced locomotor activity and the hole-board test to predict sensitivity to the conditioned rewarding effects of cocaine.

PubMed

Arenas, M Carmen; Daza-Losada, Manuel; Vidal-Infer, Antonio; Aguilar, Maria A; Miñarro, José; Rodríguez-Arias, Marta

2014-06-22

Novelty-seeking in rodents, defined as enhanced specific exploration of novel situations, is considered to predict the response of animals to drugs of abuse and, thus, allow "drug-vulnerable" individuals to be identified. The main objective of this study was to assess the predictive ability of two well-known paradigms of the novelty-seeking trait - novelty-induced locomotor activity (which distinguishes High- and Low-Responder mice, depending on their motor activity) and the hole-board test (which determines High- and Low-Novelty Seeker mice depending on the number of head dips they perform) - to identify subjects that would subsequently be more sensitive to the conditioned rewarding effects of cocaine in a population of young adult (PND 56) and adolescent (PND 35) OF1 mice of both sexes. Conditioned place preference (CPP), a useful tool for evaluating the sensitivity of individuals to the incentive properties of addictive drugs, was induced with a sub-threshold dose of cocaine (1 mg/kg, i.p.). Our results showed that novelty-induced motor activity had a greater predictive capacity to identify "vulnerable-drug" individuals among young-adult mice (PND 56), while the hole-board test was more effective in adolescents (PND 35). High-NR young-adults, which presented higher motor activity in the first ten minutes of the test (novelty-reactivity), were 3.9 times more likely to develop cocaine-induced CPP than Low-NR young-adults. When total activity (1h) was evaluated (novelty-habituation), only High-R (novelty-non-habituating) young-adult male and Low-R (novelty-habituating) female mice produced a high conditioning score. However, only High-Novelty Seeker male and female adolescents and Low-Novelty Seeker female young-adult animals (according to the hole-board test), acquired cocaine-induced CPP. These findings should contribute to the development of screening methods for identifying at-risk human drug users and prevention strategies for those with specific vulnerabilities. Copyright © 2014 Elsevier Inc. All rights reserved.

High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities

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

Sadler, Natalie C.; Webb-Robertson, Bobbie-Jo M.; Clauss, Therese R.

Cytochrome P450 monooxygenases (P450) are key to the metabolism of myriad endogenous chemicals and xenobiotics, including the majority of therapeutic drugs. Dysregulated P450 activities can lead to altered drug metabolism and toxicity, oxidative stress, and inflammation; all physiological states frequently charged as the impetus for various chronic pathologies. We characterized the impact of common xenobiotic exposures, specifically high-fat diet and active or passive cigarette smoke, on the functional capacity of hepatic and pulmonary P450s. We employed an activity-based protein profiling approach to characterize the identity and activity level of measured individual P450 isoforms. Our results confirm expectations of significant alterationsmore » in pulmonary P450s due to cigarette smoke, but now reveal the repressive impact of high-fat diet-induced obesity on many hepatic P450s activities, and the dynamic alterations due to concomitant diet and smoke exposures on liver and lung P450 activities impacting drug metabolism and pathways of inflammation.« less

Acid phosphatase activity in liver macrophage aggregates as a marker for pollution-induced immunomodulation of the non-specific immune response in fish

NASA Astrophysics Data System (ADS)

Broeg, Katja

2003-10-01

The activity of acid phosphatase in liver macrophage aggregates (MA-AP) of different fish species was used as a marker for a pollution-induced modulation of the digestive capacity of phagocytes, since functions of the non-specific immune response play a central role in the maintenance of animals' health. Based upon the investigation of more than 900 individual flounders (Platichthys flesus) and mullets (Liza aurata), natural variations, gender-specific differences and pollution-induced alterations in AP activity are demonstrated in this study. MA-AP activity was dependent on temperature and season but, nevertheless, distinctions between differently polluted areas were visible in all sampling campaigns with lowest MA-AP activity in fish from the polluted areas of the German Bight and the Israeli coast of the Mediterranean Sea. For organochlorine contaminants, as well as for mercury and copper, a significant correlation could be observed between residue concentrations in fish tissues and MA-AP activity. In all cases, except mercury which showed a positive correlation, AP activity was suppressed in animals with a high contaminant burden. MA-AP activity turned out to give reliable and consistent results for a quantification of immunomodulation in both fish species.

Mechanisms of specificity in neuronal activity-regulated gene transcription

PubMed Central

Lyons, Michelle R.; West, Anne E.

2011-01-01

The brain is a highly adaptable organ that is capable of converting sensory information into changes in neuronal function. This plasticity allows behavior to be accommodated to the environment, providing an important evolutionary advantage. Neurons convert environmental stimuli into long-lasting changes in their physiology in part through the synaptic activity-regulated transcription of new gene products. Since the neurotransmitter-dependent regulation of Fos transcription was first discovered nearly 25 years ago, a wealth of studies have enriched our understanding of the molecular pathways that mediate activity-regulated changes in gene transcription. These findings show that a broad range of signaling pathways and transcriptional regulators can be engaged by neuronal activity to sculpt complex programs of stimulus-regulated gene transcription. However, the shear scope of the transcriptional pathways engaged by neuronal activity raises the question of how specificity in the nature of the transcriptional response is achieved in order to encode physiologically relevant responses to divergent stimuli. Here we summarize the general paradigms by which neuronal activity regulates transcription while focusing on the molecular mechanisms that confer differential stimulus-, cell-type-, and developmental-specificity upon activity-regulated programs of neuronal gene transcription. In addition, we preview some of the new technologies that will advance our future understanding of the mechanisms and consequences of activity-regulated gene transcription in the brain. PMID:21620929

The use of dendrograms to describe the electrical activity of motoneurons underlying behaviors in leeches

PubMed Central

Juárez-Hernández, León J.; Bisson, Giacomo; Torre, Vincent

2013-01-01

The present manuscript aims at identifying patterns of electrical activity recorded from neurons of the leech nervous system, characterizing specific behaviors. When leeches are at rest, the electrical activity of neurons and motoneurons is poorly correlated. When leeches move their head and/or tail, in contrast, action potential (AP) firing becomes highly correlated. When the head or tail suckers detach, specific patterns of electrical activity are detected. During elongation and contraction the electrical activity of motoneurons in the Medial Anterior and Dorsal Posterior nerves increase, respectively, and several motoneurons are activated both during elongation and contraction. During crawling, swimming, and pseudo-swimming patterns of electrical activity are better described by the dendrograms of cross-correlations of motoneurons pairs. Dendrograms obtained from different animals exhibiting the same behavior are similar and by averaging these dendrograms we obtained a template underlying a given behavior. By using this template, the corresponding behavior is reliably identified from the recorded electrical activity. The analysis of dendrograms during different leech behavior reveals the fine orchestration of motoneurons firing specific to each stereotyped behavior. Therefore, dendrograms capture the subtle changes in the correlation pattern of neuronal networks when they become involved in different tasks or functions. PMID:24098274

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

PubMed Central

Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

2008-01-01

Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients. PMID:18647321

Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN.

PubMed

Iatropoulos, Paraskevas; Daina, Erica; Curreri, Manuela; Piras, Rossella; Valoti, Elisabetta; Mele, Caterina; Bresin, Elena; Gamba, Sara; Alberti, Marta; Breno, Matteo; Perna, Annalisa; Bettoni, Serena; Sabadini, Ettore; Murer, Luisa; Vivarelli, Marina; Noris, Marina; Remuzzi, Giuseppe

2018-01-01

Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment. Copyright © 2018 by the American Society of Nephrology.

Activation of MSRV-Type Endogenous Retroviruses during Infectious Mononucleosis and Epstein-Barr Virus Latency: The Missing Link with Multiple Sclerosis?

PubMed Central

Mameli, Giuseppe; Madeddu, Giordano; Mei, Alessandra; Uleri, Elena; Poddighe, Luciana; Delogu, Lucia G.; Maida, Ivana; Babudieri, Sergio; Serra, Caterina; Manetti, Roberto; Mura, Maria S.; Dolei, Antonina

2013-01-01

The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention. PMID:24236019

Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the missing link with multiple sclerosis?

PubMed

Mameli, Giuseppe; Madeddu, Giordano; Mei, Alessandra; Uleri, Elena; Poddighe, Luciana; Delogu, Lucia G; Maida, Ivana; Babudieri, Sergio; Serra, Caterina; Manetti, Roberto; Mura, Maria S; Dolei, Antonina

2013-01-01

The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention.

Preparation of porous carbon spheres from 2-keto-l-gulonic acid mother liquor by oxidation and activation for electric double-layer capacitor application.

PubMed

Hao, Zhi-Qiang; Cao, Jing-Pei; Zhao, Xiao-Yan; Wu, Yan; Zhu, Jun-Sheng; Dang, Ya-Li; Zhuang, Qi-Qi; Wei, Xian-Yong

2018-03-01

A novel strategy is proposed for the increase of specific surface area (SSA) of porous carbon sphere (PCS) by oxidation and activation. 2-keto-l-gulonic acid mother liquor (GAML) as a high-pollution waste has a relatively high value of reutilization. For its high value-added utilization, GAML is used as the precursor for preparation of PCS as carbon-based electrode materials for electric double-layer capacitor. PCS is prepared by hydrothermal carbonization, carbonization and KOH activation, and Fe(NO 3 ) 3 9H 2 O is used as an oxidizing agent during carbonization. The as-prepared PCS has excellent porosity and high SSA of 2478 m 2  g -1 . Meanwhile, the pore structure of PCS can be controlled by the adjustment of carbonization parameters (carbonization temperature and the loading of Fe(NO 3 ) 3 9H 2 O). Besides, the SSA and specific capacitance of PCS can be increased remarkably when Fe(NO 3 ) 3 9H 2 O is added in carbonization. The specific capacitance of PCS can reach 303.7 F g -1 at 40 mA g -1 . PCSs as electrode material have superior electrochemical stability. After 8000 cycles, the capacitance retention is 98.3% at 2 A g -1 . The electric double-layer capacitance of PCS is improved when CS is carbonized with Fe(NO 3 ) 3 9H 2 O, and the economic and environmental benefits are achieved by the effective recycle of GAML. Copyright © 2017 Elsevier Inc. All rights reserved.

Technological properties of indigenous wine yeast strains isolated from wine production regions of Turkey.

PubMed

Bağder Elmacı, Simel; Özçelik, Filiz; Tokatlı, Mehmet; Çakır, İbrahim

2014-05-01

The purpose of this study was to evaluate the important technological and fermentative properties of wine yeast strains previously isolated from different wine producing regions of Turkey. The determination of the following important properties was made: growth at high temperatures; fermentative capability in the presence of high sugar concentration; fermentation rate; hydrogen sulfide production; killer activity; resistance to high ethanol and sulfur dioxide; foam production; and enzymatic profiles. Ten local wine yeast strains belonging to Saccharomyces, and one commercial active dry yeast as a reference strain were evaluated. Fermentation characteristics were evaluated in terms of kinetic parameters, including ethanol yield (YP/S), biomass yield (YX/S), theoretical ethanol yield (%), specific ethanol production rate (qp; g/gh), specific glucose uptake rate (qs; g/gh), and the substrate conversion (%). All tested strains were able to grow at 37 °C and to start fermentation at 30° Brix, and were resistant to high concentrations of sulfur dioxide. 60 % of the strains were weak H2S producers, while the others produced high levels. Foam production was high, and no strains had killer activity. Six of the tested strains had the ability to grow and ferment at concentrations of 14 % ethanol. Except for one strain, all fermented most of the media sugars at a high rate, producing 11.0-12.4 % (v/v) ethanol. Although all but one strain had suitable characteristics for wine production, they possessed poor activities of glycosidase, esterase and proteinase enzymes of oenological interest. Nine of the ten local yeast strains were selected for their good oenological properties and their suitability as a wine starter culture.

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity.

PubMed

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma.

Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

PubMed Central

Xu, Peng; Andreasen, Peter A.; Huang, Mingdong

2017-01-01

This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively. The following affinity maturations significantly enhanced the potencies of the two peptides, 10-fold and >250-fold for upain-1 and mupain-1, respectively. The most potent muPA inhibitor has a potency (Ki = 2 nM) and specificity comparable to mono-clonal antibodies. Furthermore, we also found an unusual feature of mupain-1 that its inhibitory potency can be enhanced by increasing the flexibility, which challenges the traditional viewpoint that higher rigidity leading to higher affinity. Moreover, by changing a few key residues, we converted mupain-1 from a uPA inhibitor to inhibitors of other serine proteases, including plasma kallikrein (PK) and coagulation factor XIa (fXIa). PK and fXIa inhibitors showed Ki values in the low nanomolar range and high specificity. Our studies demonstrate the versatility of small cyclic peptides to engineer inhibitory potency against serine proteases and to provide a new strategy for generating peptide inhibitors of serine proteases. PMID:29104489

Comparative Normal/Failing Rat Myocardium Cell Membrane Chromatographic Analysis System for Screening Specific Components That Counteract Doxorubicin-Induced Heart Failure from Acontium carmichaeli

PubMed Central

2015-01-01

Cell membrane chromatography (CMC) derived from pathological tissues is ideal for screening specific components acting on specific diseases from complex medicines owing to the maximum simulation of in vivo drug-receptor interactions. However, there are no pathological tissue-derived CMC models that have ever been developed, as well as no visualized affinity comparison of potential active components between normal and pathological CMC columns. In this study, a novel comparative normal/failing rat myocardium CMC analysis system based on online column selection and comprehensive two-dimensional (2D) chromatography/monolithic column/time-of-flight mass spectrometry was developed for parallel comparison of the chromatographic behaviors on both normal and pathological CMC columns, as well as rapid screening of the specific therapeutic agents that counteract doxorubicin (DOX)-induced heart failure from Acontium carmichaeli (Fuzi). In total, 16 potential active alkaloid components with similar structures in Fuzi were retained on both normal and failing myocardium CMC models. Most of them had obvious decreases of affinities on failing myocardium CMC compared with normal CMC model except for four components, talatizamine (TALA), 14-acetyl-TALA, hetisine, and 14-benzoylneoline. One compound TALA with the highest affinity was isolated for further in vitro pharmacodynamic validation and target identification to validate the screen results. Voltage-dependent K+ channel was confirmed as a binding target of TALA and 14-acetyl-TALA with high affinities. The online high throughput comparative CMC analysis method is suitable for screening specific active components from herbal medicines by increasing the specificity of screened results and can also be applied to other biological chromatography models. PMID:24731167

A rapid screening method to detect specific inhibitors of pyruvate orthophosphate dikinase as leads for C4 plant-selective herbicides.

PubMed

Doyle, Jason R; Burnell, James N; Haines, Dianne S; Llewellyn, Lyndon E; Motti, Cherie A; Tapiolas, Dianne M

2005-02-01

Plants using the C(4) photosynthetic pathway are highly represented among the world's worst weeds, with only 4 C(4) species being agriculturally productive (maize, sorghum, millet, and sugar cane). With the C(4) acid cycle operating as a biochemical appendage of C(3) photosynthesis, the additional enzymes involved in C(4) photosynthesis represent an attractive target for the development of weed-specific herbicides. The rate-limiting enzyme of this metabolic pathway is pyruvate orthophosphate dikinase (PPDK). PPDK, coupled with phosphoenolpyruvate carboxylase and nicotinamide adenine dinucleotide-malate dehydrogenase, was used to develop a microplate-based assay to detect inhibitors of enzymes of the C(4) acid cycle. The resulting assay had a Z' factor of 0.61, making it a high-quality assay able to reliably identify active test samples. Organic extracts of 6679 marine macroscopic organisms were tested within the assay, and 343 were identified that inhibited the 3 enzyme-coupled reaction. A high confirmation rate was achieved, with 95% of these hit extracts proving active again upon retesting. Sequential addition of phosphoenolpyruvate and oxaloacetate to the assay facilitated identification of 83 extracts that specifically inhibited PPDK.

Synthesis of a highly efficient 3D graphene-CNT-MnO2-PANI nanocomposite as a binder free electrode material for supercapacitors.

PubMed

Asif, Muhammad; Tan, Yi; Pan, Lujun; Rashad, Muhammad; Li, Jiayan; Fu, Xin; Cui, Ruixue

2016-09-29

Graphene based nanocomposites have been investigated intensively, as electrode materials for energy storage applications. In the current work, a graphene-CNT-MnO 2 -PANI (GCM@PANI) nanocomposite has been synthesized on 3D graphene grown on nickel foam, as a highly efficient binder free electrode material for supercapacitors. Interestingly, the specific capacitance of the synthesized electrode increases up to the first 1500 charge-discharge cycles, and is thus referred to as an electrode activation process. The activated GCM@PANI nanocomposite electrode exhibits an extraordinary galvanostatic specific capacitance of 3037 F g -1 at a current density of 8 A g -1 . The synthesized nanocomposite exhibits an excellent cyclic stability with a capacitance retention of 83% over 12 000 charge-discharge cycles, and a high rate capability by retaining a specific capacitance of 84.6% at a current density of 20 A g -1 . The structural and electrochemical analysis of the synthesized nanocomposite suggests that the astonishing electrochemical performance might be attributed to the growth of a novel PANI nanoparticle layer and the synergistic effect of CNT/MnO 2 nanostructures.

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2018-01-01

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

The neural correlates of dreaming.

PubMed

Siclari, Francesca; Baird, Benjamin; Perogamvros, Lampros; Bernardi, Giulio; LaRocque, Joshua J; Riedner, Brady; Boly, Melanie; Postle, Bradley R; Tononi, Giulio

2017-06-01

Consciousness never fades during waking. However, when awakened from sleep, we sometimes recall dreams and sometimes recall no experiences. Traditionally, dreaming has been identified with rapid eye-movement (REM) sleep, characterized by wake-like, globally 'activated', high-frequency electroencephalographic activity. However, dreaming also occurs in non-REM (NREM) sleep, characterized by prominent low-frequency activity. This challenges our understanding of the neural correlates of conscious experiences in sleep. Using high-density electroencephalography, we contrasted the presence and absence of dreaming in NREM and REM sleep. In both NREM and REM sleep, reports of dream experience were associated with local decreases in low-frequency activity in posterior cortical regions. High-frequency activity in these regions correlated with specific dream contents. Monitoring this posterior 'hot zone' in real time predicted whether an individual reported dreaming or the absence of dream experiences during NREM sleep, suggesting that it may constitute a core correlate of conscious experiences in sleep.

Post-growth process for flexible CdS/CdTe thin film solar cells with high specific power.

PubMed

Cho, Eunwoo; Kang, Yoonmook; Kim, Donghwan; Kim, Jihyun

2016-05-16

We demonstrated a flexible CdS/CdTe thin film solar cell with high specific power of approximately 254 W/kg. A flexible and ultra-light weight CdS/CdTe cell treated with pre-NP etch process exhibited high conversion efficiency of 13.56% in superstrate configuration. Morphological, structural and optical changes of CdS/CdTe thin films were characterized when pre-NP etch step was incorporated to the conventional post-deposition process. Improvement of photovoltaic parameters can be attributed to the removal of the oxide and the formation of Te-rich layer, which benefit the activation process. Pre-NP etched cell maintained their flexibility and performance under the repeated tensile strain of 0.13%. Our method can pave a way for manufacturing flexible CdS/CdTe thin film solar cells with high specific power for mobile and aerospace applications.

Generation of TALE-Based Designer Epigenome Modifiers.

PubMed

Nitsch, Sandra; Mussolino, Claudio

2018-01-01

Manipulation of gene expression can be facilitated by editing the genome or the epigenome. Precise genome editing is traditionally achieved by using designer nucleases which are generally exploited to eliminate a specific gene product. Upon the introduction of a site-specific DNA double-strand break (DSB) by the nuclease, endogenous DSB repair mechanisms are in turn harnessed to induce DNA sequence changes that can result in target gene inactivation. Minimal off-target effects can be obtained by endowing designer nucleases with the highly specific DNA-binding domain (DBD) derived from transcription activator-like effectors (TALEs). In contrast, epigenome editing allows gene expression control without inducing changes in the DNA sequence by specifically altering epigenetic marks, as histone tails modifications or DNA methylation patterns within promoter or enhancer regions. Importantly, this approach allows both up- and downregulation of the target gene expression, and the effect is generally reversible. TALE-based designer epigenome modifiers combine the high specificity of TALE-derived DBDs with the power of epigenetic modifier domains to induce fast and long-lasting changes in the epigenetic landscape of a target gene and control its expression. Here we provide a detailed description for the generation of TALE-based designer epigenome modifiers and of a suitable reporter cell line to easily monitor their activity.

Silicon oxide based high capacity anode materials for lithium ion batteries

DOEpatents

Deng, Haixia; Han, Yongbong; Masarapu, Charan; Anguchamy, Yogesh Kumar; Lopez, Herman A.; Kumar, Sujeet

2017-03-21

Silicon oxide based materials, including composites with various electrical conductive compositions, are formulated into desirable anodes. The anodes can be effectively combined into lithium ion batteries with high capacity cathode materials. In some formulations, supplemental lithium can be used to stabilize cycling as well as to reduce effects of first cycle irreversible capacity loss. Batteries are described with surprisingly good cycling properties with good specific capacities with respect to both cathode active weights and anode active weights.