[Automatic social behavior: how does activation of the concepts of egoism and altruism influence helping behavior?].

PubMed

Walther, E; Müller, D; Schott, O

2001-01-01

An experimental study investigated the influence of priming on helping behavior. A scrambled sentence test was used to prime groups with the concepts of altruism or egoism. In a third group a neutral concept was activated. The results indicated that there is no difference in helping behavior between the altruism and the neutral group. However, in the egoism priming condition participants showed higher latencies and helped less often than participants in both other conditions.

Subjective craving and event-related brain response to olfactory and visual chocolate cues in binge-eating and healthy individuals.

PubMed

Wolz, I; Sauvaget, A; Granero, R; Mestre-Bach, G; Baño, M; Martín-Romera, V; Veciana de Las Heras, M; Jiménez-Murcia, S; Jansen, A; Roefs, A; Fernández-Aranda, F

2017-02-03

High-sugar/high-fat foods are related to binge-eating behaviour and especially people with low inhibitory control may encounter elevated difficulties to resist their intake. Incentive sensitization to food-related cues might lead to increased motivated attention towards these stimuli and to cue-induced craving. To investigate the combined influence of olfactory and visual stimuli on craving, inhibitory control and motivated attention, 20 healthy controls and 19 individuals with binge-eating viewed chocolate and neutral pictures, primed by chocolate or neutral odours. Subjective craving and electroencephalogram activity were recorded during the task. N2 and Late Positive Potential (LPP) amplitudes were analysed. Patients reported higher craving than controls. Subjective craving, N2 and LPP amplitudes were higher for chocolate versus neutral pictures. Patients showed a higher relative increase in N2 amplitudes to chocolate versus neutral pictures than controls. Chocolate images induced significant increases in craving, motivated attention and measures of cognitive control. Chocolate odour might potentiate the craving response to visual stimuli, especially in patients with binge-eating.

Subjective craving and event-related brain response to olfactory and visual chocolate cues in binge-eating and healthy individuals

PubMed Central

Wolz, I.; Sauvaget, A.; Granero, R.; Mestre-Bach, G.; Baño, M.; Martín-Romera, V.; Veciana de las Heras, M.; Jiménez-Murcia, S.; Jansen, A.; Roefs, A.; Fernández-Aranda, F.

2017-01-01

High-sugar/high-fat foods are related to binge-eating behaviour and especially people with low inhibitory control may encounter elevated difficulties to resist their intake. Incentive sensitization to food-related cues might lead to increased motivated attention towards these stimuli and to cue-induced craving. To investigate the combined influence of olfactory and visual stimuli on craving, inhibitory control and motivated attention, 20 healthy controls and 19 individuals with binge-eating viewed chocolate and neutral pictures, primed by chocolate or neutral odours. Subjective craving and electroencephalogram activity were recorded during the task. N2 and Late Positive Potential (LPP) amplitudes were analysed. Patients reported higher craving than controls. Subjective craving, N2 and LPP amplitudes were higher for chocolate versus neutral pictures. Patients showed a higher relative increase in N2 amplitudes to chocolate versus neutral pictures than controls. Chocolate images induced significant increases in craving, motivated attention and measures of cognitive control. Chocolate odour might potentiate the craving response to visual stimuli, especially in patients with binge-eating. PMID:28155875

Non-neutralized Electric Currents in Solar Active Regions and Flare Productivity

NASA Astrophysics Data System (ADS)

Kontogiannis, Ioannis; Georgoulis, Manolis K.; Park, Sung-Hong; Guerra, Jordan A.

2017-11-01

We explore the association of non-neutralized currents with solar flare occurrence in a sizable sample of observations, aiming to show the potential of such currents in solar flare prediction. We used the high-quality vector magnetograms that are regularly produced by the Helioseismic Magnetic Imager, and more specifically, the Space weather HMI Active Region Patches (SHARP). Through a newly established method that incorporates detailed error analysis, we calculated the non-neutralized currents contained in active regions (AR). Two predictors were produced, namely the total and the maximum unsigned non-neutralized current. Both were tested in AR time-series and a representative sample of point-in-time observations during the interval 2012 - 2016. The average values of non-neutralized currents in flaring active regions are higher by more than an order of magnitude than in non-flaring regions and correlate very well with the corresponding flare index. The temporal evolution of these parameters appears to be connected to physical processes, such as flux emergence and/or magnetic polarity inversion line formation, that are associated with increased solar flare activity. Using Bayesian inference of flaring probabilities, we show that the total unsigned non-neutralized current significantly outperforms the total unsigned magnetic flux and other well-established current-related predictors. It therefore shows good prospects for inclusion in an operational flare-forecasting service. We plan to use the new predictor in the framework of the FLARECAST project along with other highly performing predictors.

[Virus strain specific serum neutralizing antibodies in children and adolescents immunized with a Russian mumps vaccine].

PubMed

Otrashevskaia, E V; Krasil'nikov, I V; Ignat'ev, G M

2010-01-01

Postvaccination immunity was studied in the children and teenagers without a history of clinical mumps infection, who had been immunized with the Leningrad-3 mumps vaccine. The level of specific lgG in ELISA and that and spectrum of their neutralizing activity against a vaccine strain and three heterologous mumps virus (MV) strains (genotypes A, C, and H) were measured. The investigation included 151 sera from the vaccinees aged 3 to 17 years, possessing the detectable specific IgG titers in ELISA and the detectable neutralizing titers against the vaccine strain. 97.4% of the vaccinees had neutralizing activity against 1-3 heterologous MV strains. A preponderance of neutralizing titers against heterologous MV strains by 1-log2 in some sera (6.5-32.5 depending on age) was most likely to suggest that the vaccinees' had been in contact with these virus strains in the past. In our investigation, a combination of positive IgG titers and neutralizing titers against the vaccine strain 2-log2 or higher provided the protection of the vaccinated children and teenagers against the symptomatic infection. There was a pronounced buster effect of the second immunization and a drop in the neutralizing activity of the sera from the vaccinated children and adolescents over time after the first and second immunization.

Observations of Thermospheric Horizontal Winds at Watson Lake, Yukon Territory (lambda=65 Deg N)

NASA Technical Reports Server (NTRS)

Niciejewski, R. J.; Killeen, T. L.; Solomon, Stanley C.

1996-01-01

Fabry-Perot interferometer observations of the thermospheric O I (6300 A) emission have been conducted from an airglow observatory at a dark field site in the southeastern Yukon Territory, Canada, for the period November 1991 to April 1993. The experiment operated in unattended, remote fashion, has resulted in a substantial data set from which mean neutral winds have been determined. Dependent upon geomagnetic activity, the nocturnal location of the site is either equatorward of the auroral oval or within oval boundaries. The data set is rich enough to permit hourly binning of neutral winds based upon the K(sub p) geomagnetic disturbance index as well as the season. For cases of low geomagnetic activity the averaged vector horizontal neutral wind exhibits the characteristics of a midlatitude site displaying antisunward pressure-gradient-driven winds. As the geomagnetic activity rises in the late afternoon and evening winds slowly rotate sunward in an anticlockwise direction, initially remaining near 100 m/s in speed but eventually increasing to 300 m/s for K(sub p) greater than 5. For the higher levels of activity the observed neutral wind flow pattern resembles a higher-latitude polar cap pattern characterized by ion drag forcing of thermospheric neutral gases. In addition, rotational Coriolis forcing on the dusk side enhances the ion drag forcing, resulting in dusk winds which trace out the clockwise dusk cell plasma flow. On the dawn side the neutral winds also rotate in an anticlockwise direction as the strength of geomagnetic disturbances increase. Since the site is located at a transition latitude between the midlatitude and the polar cap the data set provides a sensitive test for general circulation models which attempt to parameterize the contribution of magnetospheric processes. A comparison with the Vector Spherical Harmonic (VSH) model indicates several regions of poor correspondence for December solstice conditions but reasonable agreement for the vernal equinox.

Differential profiles and inhibitory effect on rotavirus vaccines of nonantibody components in breast milk from mothers in developing and developed countries.

PubMed

Moon, Sung-Sil; Tate, Jacqueline E; Ray, Pratima; Dennehy, Penelope H; Archary, Derseree; Coutsoudis, Anna; Bland, Ruth; Newell, Marie-Louise; Glass, Roger I; Parashar, Umesh; Jiang, Baoming

2013-08-01

Live oral rotavirus vaccines have been less immunogenic and efficacious for children of developing countries than for those in middle income and industrialized countries, and the basis for these differences is not fully understood. Recently, we demonstrated that breastmilk from mothers in India had significantly higher IgA and neutralizing activity against rotavirus that could reduce the effective titer of rotavirus vaccines reaching the gut when compared with that from mothers in the United States. We extended our study to understand the specific contribution of those nonantibody components in breastmilk to the neutralizing activity against rotavirus vaccine we observed. Breastmilk samples were collected from mothers of breast-feeding infants aged between 4 and 29 weeks (ie, vaccine eligible age) in India (N = 40), South Africa (N = 50) and the United States (N = 51). We examined breastmilk for lactoferrin, lactadherin, rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains (Rotarix, RotaTeq G1 and 116E) using enzyme immunoassays, a plaque reduction assay or a microneutralization assay. We observed higher levels of lactoferrin, lactadherin, IgA and neutralizing activity in breastmilk specimens from Indian and South African women than those from American women. We demonstrated positive associations between levels of lactoferrin or IgA and neutralizing activity in Indian and South African specimens, but not in American specimens. We demonstrated that the inhibitory effect of lactoferrin was dose- or species-dependent, as evidenced by greater reduction in titer of Rotarix and 116E by human lactoferrin. Lactadherin also exhibited inhibitory activity to rotavirus vaccines but appeared to be less effective. The lower immunogenicity and efficacy of rotavirus vaccines in developing countries could be explained, in part, by synergistic inhibitory effect of high levels of antibody and nonantibody components in breastmilk consumed by infants at the time of immunization. Therefore, there is a need for alternative rotavirus vaccine strategies in breast-feeding populations.

Optical mapping of prefrontal brain connectivity and activation during emotion anticipation.

PubMed

Wang, Meng-Yun; Lu, Feng-Mei; Hu, Zhishan; Zhang, Juan; Yuan, Zhen

2018-09-17

Accumulated neuroimaging evidence shows that the dorsal lateral prefrontal cortex (dlPFC) is activated during emotion anticipation. The aim of this work is to examine the brain connectivity and activation differences in dlPFC between the positive, neutral and negative emotion anticipation by using functional near-infrared spectroscopy (fNIRS). The hemodynamic responses were first assessed for all subjects during the performance of various emotion anticipation tasks. And then small-world analysis was performed, in which the small-world network indicators including the clustering coefficient, average path length, average node degree, and measure of small-world index were calculated for the functional brain networks associated with the positive, neutral and negative emotion anticipation, respectively. We discovered that compared to negative and neutral emotion anticipation, the positive one exhibited enhanced brain activation in the left dlPFC. Although the functional brain networks for the three emotion anticipation cases manifested the small-world properties regarding the clustering coefficient, average path length, average node degree, and measure of small-world index, the positive one showed significantly higher clustering coefficient and shorter average path length than those from the neutral and negative cases. Consequently, the small-world network indicators and brain activation in dlPPC were able to distinguish well between the positive, neutral and negative emotion anticipation. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of emotional processing on working memory in schizophrenia.

PubMed

Becerril, Karla; Barch, Deanna

2011-09-01

Research on emotional processing in schizophrenia suggests relatively intact subjective responses to affective stimuli "in the moment." However, neuroimaging evidence suggests diminished activation in brain regions associated with emotional processing in schizophrenia. We asked whether given a more vulnerable cognitive system in schizophrenia, individuals with this disorder would show increased or decreased modulation of working memory (WM) as a function of the emotional content of stimuli compared with healthy control subjects. In addition, we examined whether higher anhedonia levels were associated with a diminished impact of emotion on behavioral and brain activation responses. In the present study, 38 individuals with schizophrenia and 32 healthy individuals completed blocks of a 2-back WM task in a functional magnetic resonance imaging scanning session. Blocks contained faces displaying either only neutral stimuli or neutral and emotional stimuli (happy or fearful faces), randomly intermixed and occurring both as targets and non-targets. Both groups showed higher accuracy but slower reaction time for negative compared to neutral stimuli. Individuals with schizophrenia showed intact amygdala activity in response to emotionally evocative stimuli, but demonstrated altered dorsolateral prefrontal cortex (DLPFC) and hippocampal activity while performing an emotionally loaded WM-task. Higher levels of social anhedonia were associated with diminished amygdala responses to emotional stimuli and increased DLPFC activity in individuals with schizophrenia. Emotional arousal may challenge dorsal-frontal control systems, which may have both beneficial and detrimental influences. Our findings suggest that disturbances in emotional processing in schizophrenia relate to alterations in emotion-cognition interactions rather than to the perception and subjective experience of emotion per se.

Some articulatory details of emotional speech

NASA Astrophysics Data System (ADS)

Lee, Sungbok; Yildirim, Serdar; Bulut, Murtaza; Kazemzadeh, Abe; Narayanan, Shrikanth

2005-09-01

Differences in speech articulation among four emotion types, neutral, anger, sadness, and happiness are investigated by analyzing tongue tip, jaw, and lip movement data collected from one male and one female speaker of American English. The data were collected using an electromagnetic articulography (EMA) system while subjects produce simulated emotional speech. Pitch, root-mean-square (rms) energy and the first three formants were estimated for vowel segments. For both speakers, angry speech exhibited the largest rms energy and largest articulatory activity in terms of displacement range and movement speed. Happy speech is characterized by largest pitch variability. It has higher rms energy than neutral speech but articulatory activity is rather comparable to, or less than, neutral speech. That is, happy speech is more prominent in voicing activity than in articulation. Sad speech exhibits longest sentence duration and lower rms energy. However, its articulatory activity is no less than neutral speech. Interestingly, for the male speaker, articulation for vowels in sad speech is consistently more peripheral (i.e., more forwarded displacements) when compared to other emotions. However, this does not hold for female subject. These and other results will be discussed in detail with associated acoustics and perceived emotional qualities. [Work supported by NIH.

Smaller external notebook mice have different effects on posture and muscle activity.

PubMed

Oude Hengel, Karen M; Houwink, Annemieke; Odell, Dan; van Dieën, Jaap H; Dennerlein, Jack T

2008-07-01

Extensive computer mouse use is an identified risk factor for computer work-related musculoskeletal disorders; however, notebook computer mouse designs of varying sizes have not been formally evaluated but may affect biomechanical risk factors. Thirty adults performed a set of mouse tasks with five notebook mice, ranging in length from 75 to 105 mm and in width from 35 to 65 mm, and a reference desktop mouse. An electro-magnetic motion analysis system measured index finger (metacarpophalangeal joint), wrist and forearm postures, and surface electromyography measured muscle activity of three extensor muscles in the forearm and the first dorsal interosseus. The smallest notebook mice were found to promote less neutral postures (up to 3.2 degrees higher metacarpophalangeal joint adduction; 6.5 degrees higher metacarpophalangeal joint flexion, 2.3 degrees higher wrist extension) and higher muscle activity (up to 4.1% of maximum voluntary contraction higher wrist extensor muscle activity). Participants with smaller hands had overall more non-neutral postures than participants with larger hands (up to 5.6 degrees higher wrist extension and 5.9 degrees higher pronation); while participants with larger hands were more influenced by the smallest notebook mice (up to 3.6 degrees higher wrist extension and 5.5% of maximum voluntary contraction higher wrist extensor values). Self-reported ratings showed that while participants preferred smaller mice for portability; larger mice scored higher on comfort and usability. The smallest notebook mice increased the intensity of biomechanical exposures. Longer term mouse use could enhance these differences, having a potential impact on the prevention of work-related musculoskeletal disorders.

HIV-Neutralizing Activity of Cationic Polypeptides in Cervicovaginal Secretions of Women in HIV-Serodiscordant Relationships

PubMed Central

Levinson, Pauline; Choi, Robert Y.; Cole, Amy L.; Hirbod, Taha; Rhedin, Samuel; Payne, Barbara; Guthrie, Brandon L.; Bosire, Rose; Cole, Alexander M.; Farquhar, Carey; Broliden, Kristina

2012-01-01

Background HIV exposed seronegative (HESN) women represent the population most in need of a prophylactic antiviral strategy. Mucosal cationic polypeptides can potentially be regulated for this purpose and we here aimed to determine their endogenous expression and HIV neutralizing activity in genital secretions of women at risk of HIV infection. Methodology/Principal Findings Cervicovaginal secretions (CVS) of Kenyan women in HIV-serodiscordant relationships (HESN, n = 164; HIV seropositive, n = 60) and low-risk controls (n = 72) were assessed for the cationic polypeptides HNP1–3, LL-37 and SLPI by ELISA and for HIV neutralizing activity by a PBMC-based assay using an HIV primary isolate. Median levels of HNP1–3 and LL-37 in CVS were similar across study groups. Neither HSV-2 serostatus, nor presence of bacterial vaginosis, correlated with levels of HNP1–3 or LL-37 in the HESN women. However, an association with their partner's viral load was observed. High viral load (>10,000 HIV RNA copies/ml plasma) correlated with higher levels of HNP1–3 and LL-37 (p = 0.04 and 0.03, respectively). SLPI was most abundant in the low-risk group and did not correlate with male partner's viral load in the HESN women. HIV neutralizing activity was found in CVS of all study groups. In experimental studies, selective depletion of cationic polypeptides from CVS rendered the remaining CVS fraction non-neutralizing, whereas the cationic polypeptide fraction retained the activity. Furthermore, recombinant HNP1–3 and LL-37 could induce neutralizing activity when added to CVS lacking intrinsic activity. Conclusions/Significance These findings show that CVS from HESN, low-risk, and HIV seropositive women contain HIV neutralizing activity. Although several innate immune proteins, including HNP1–3 and LL-37, contribute to this activity these molecules can also have inflammatory properties. This balance is influenced by hormonal and environmental factors and in the present HIV serodiscordant couple cohort study we show that a partner's viral load is associated with levels of such molecules. PMID:22389677

Human neutral brush border endopeptidase EC 3.4.24.11 in urine, its isolation, characterisation and activity in renal diseases.

PubMed

Vlaskou, D; Hofmann, W; Guder, W G; Siskos, P A; Dionyssiou-Asteriou, A

2000-07-01

Human neutral brush border endopeptidase (NEP) was purified from the urine of patients suffering from acute toxic tubulointerstitial nephropathy. An enzyme preparation with specific activity of 102 Ug(-1) protein was obtained. The urinary activities of neutral endopeptidase and alanine aminopeptidase were measured in patients with renal disease and in 30 control patients, resulting in a reference range from 0.1 to 0.7 Ug(-1) creatinine and 1.4-14.1 Ug(-1) creatinine, respectively. Urine enzyme activities were highest in patients with acute tubulotoxic renal diseases. Neutral endopeptidase and alanine aminopeptidase activities were found to be 6.5- and 10-fold higher than the upper value of the reference range, respectively. Smaller increases in the rate of excretion of these enzymes (2.5- and 3.5-fold), respectively, were observed in patients suffering from acute tubular insufficiency and even lower increases, 2- and 1.5-fold, respectively, were observed in patients with chronic renal diseases. In diabetics and kidney transplant patients the enzyme excretion rates were within the reference range. Assay of both transmembrane metalloproteinases in urine may prove valuable in serving as markers for renal toxicity. Together with beta-NAG these enzymes could be employed as differentiation markers between acute and chronic tubular insufficiency.

Development of a new polyspecific antivenom for snakebite envenoming in Sri Lanka: Analysis of its preclinical efficacy as compared to a currently available antivenom.

PubMed

Villalta, Mauren; Sánchez, Andrés; Herrera, María; Vargas, Mariángela; Segura, Álvaro; Cerdas, Maykel; Estrada, Ricardo; Gawarammana, Indika; Keyler, Dan E; McWhorter, Kimberly; Malleappah, Roy; Alape-Girón, Alberto; León, Guillermo; Gutiérrez, José María

2016-11-01

A new whole IgG, freeze-dried, polyspecific antivenom was prepared from the plasma of horses immunized with the venoms of the snakes Daboia russelii, Echis carinatus, Hypnale hypnale, and Naja naja from Sri Lanka. The preclinical neutralizing ability of this antivenom against several toxic and enzymatic activities of these four venoms was analyzed, and compared with that of a batch of VINS antivenom (India) being currently used in Sri Lanka. The activities tested were: lethality, hemorrhagic, in vitro coagulant, proteinase and phospholipase A 2 . Both antivenoms neutralized, to a different extent, these activities of the venom of D. russelii, E. carinatus, and N. naja. In general, the polyspecific Sri Lankan antivenom was more effective than the Indian antivenom in the neutralization of the venoms of D. russelii and E. carinatus, whereas the Indian antivenom showed a higher efficacy against the venom of N. naja. Regarding H. hypnale, the new Sri Lankan antivenom was effective in the neutralization of all activities tested, whereas the Indian antivenom neutralized lethality but not hemorrhagic, coagulant, proteinase and PLA 2 activities, in agreement with the fact that this venom is not included in the immunization mixture for this antivenom. Results suggest that the new polyspecific Sri Lankan antivenom has a satisfactory preclinical neutralizing profile and compares favorably with the Indian antivenom. This is ready to be tested in a clinical trial to evaluate its efficacy and safety in human victims of snakebite envenomings by D. russelii, E. carinatus and H. hypnale in Sri Lanka. Copyright © 2016 Elsevier Ltd. All rights reserved.

Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41

PubMed Central

Seaman, Mike S.; Lutje Hulsik, David; Hinz, Andreas; Vanzetta, Fabrizia; Agatic, Gloria; Silacci, Chiara; Mainetti, Lara; Scarlatti, Gabriella; Sallusto, Federica; Weiss, Robin; Lanzavecchia, Antonio; Weissenhorn, Winfried

2010-01-01

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool. PMID:21124990

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

PubMed

Sabin, Charles; Corti, Davide; Buzon, Victor; Seaman, Mike S; Lutje Hulsik, David; Hinz, Andreas; Vanzetta, Fabrizia; Agatic, Gloria; Silacci, Chiara; Mainetti, Lara; Scarlatti, Gabriella; Sallusto, Federica; Weiss, Robin; Lanzavecchia, Antonio; Weissenhorn, Winfried

2010-11-18

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

Does excessive play of violent first-person-shooter-video-games dampen brain activity in response to emotional stimuli?

PubMed

Montag, Christian; Weber, Bernd; Trautner, Peter; Newport, Beate; Markett, Sebastian; Walter, Nora T; Felten, Andrea; Reuter, Martin

2012-01-01

The present case-control study investigated the processing of emotional pictures in excessive first-person-shooter-video-players and control persons. All participants of the fMRI experiment were confronted with pictures from four categories including pleasant, unpleasant, neutral content and pictures from the first-person-shooter-video-game 'Counterstrike'. Compared to controls, gamers showed a significantly lower activation of the left lateral medial frontal lobe while processing negative emotions. Another interesting finding of the study represents the higher activation of frontal and temporal brain areas in gamers when processing screen-shots from the first-person-shooter-video-game 'Counterstrike'. Higher brain activity in the lateral prefrontal cortex could represent a protection mechanism against experiencing negative emotions by down-regulating limbic brain activity. Due to a frequent confrontation with violent scenes, the first-person-shooter-video-gamers might have habituated to the effects of unpleasant stimuli resulting in lower brain activation. Individual differences in brain activations of the contrast Counterstrike>neutral pictures potentially resemble the activation of action-scripts related to the video-game. Copyright © 2011 Elsevier B.V. All rights reserved.

[Soil hydrolase characteristics in late soil-thawing period in subalpine/alpine forests of west Sichuan].

PubMed

Tan, Bo; Wu, Fu-Zhong; Yang, Wan-Qin; Yu, Sheng; Yang, Yu-Lian; Wang, Ao

2011-05-01

Late soil-thawing period is a critical stage connecting winter and growth season. The significant temperature fluctuation at this stage might have strong effects on soil ecological processes. In order to understand the soil biochemical processes at this stage in the subalpine/alpine forests of west Sichuan, soil samples were collected from the representative forests including primary fir forest, fir and birch mixed forest, and secondary fir forest in March 5-April 25, 2009, with the activities of soil invertase, urease, and phosphatase (neutral, acid and alkaline phosphatases) measured. In soil frozen period, the activities of the three enzymes in test forests still kept relatively higher. With the increase of soil temperature, the activities of hydrolases at the early stage of soil-thawing decreased rapidly after a sharp increase, except for neutral phosphatease. Thereafter, there was an increase in the activities of urease and phosphatase. Relative to soil mineral layer, soil organic layer had higher hydrolase activity in late soil-thawing period, and showed more obvious responses to the variation of soil temperature.

Inhibitory effect of breast milk on infectivity of live oral rotavirus vaccines.

PubMed

Moon, Sung-Sil; Wang, Yuhuan; Shane, Andi L; Nguyen, Trang; Ray, Pratima; Dennehy, Penelope; Baek, Luck Ju; Parashar, Umesh; Glass, Roger I; Jiang, Baoming

2010-10-01

Live oral rotavirus vaccines have been less immunogenic and efficacious among children in poor developing countries compared with middle income and industrialized countries for reasons that are not yet completely understood. We assessed whether the neutralizing activity of breast milk could lower the titer of vaccine virus and explain this difference in vitro. Breast milk samples were collected from mothers who were breast-feeding infants 4 to 29 weeks of age (ie, vaccine eligible age) in India (N = 40), Vietnam (N = 77), South Korea (N = 34), and the United States (N = 51). We examined breast milk for rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains-RV1, RV5 G1, and 116E using enzyme immunoassays. The inhibitory effect of breast milk on RV1 was further examined by a plaque reduction assay. Breast milk from Indian women had the highest IgA and neutralizing titers against all 3 vaccine strains, while lower but comparable median IgA and neutralizing titers were detected in breast milk from Korean and Vietnamese women, and the lowest titers were seen in American women. Neutralizing activity was greatest against the 2 vaccine strains of human origin, RV1 and 116E. This neutralizing activity in one half of the breast milk specimens from Indian women could reduce the effective titer of RV1 by ∼2 logs, of 116E by 1.5 logs, and RV5 G1 strain by ∼1 log more than that of breast milk from American women. The lower immunogenicity and efficacy of rotavirus vaccines in poor developing countries could be explained, in part, by higher titers of IgA and neutralizing activity in breast milk consumed by their infants at the time of immunization that could effectively reduce the potency of the vaccine. Strategies to overcome this negative effect, such as delaying breast-feeding at the time of immunization, should be evaluated.

Changes in the biological activity of heavy metal- and oil-polluted soils in urban recreation territories

NASA Astrophysics Data System (ADS)

Trifonova, T. A.; Zabelina, O. N.

2017-04-01

Urban recreation areas of different sizes were investigated in the city of Vladimir. The degree of their contamination with heavy metals and oil products was revealed. The content of heavy metals exceeded their maximum permissible concentrations by more than 2.5 times. The total content of heavy metals decreased in the sequence: Zn > Pb > Co > Mn > Cr > Ni. The mass fraction of oil products in the studied soils varied within the range of 0.016-0.28 mg/g. The reaction of soils in public gardens and a boulevard was neutral or close to neutral; in some soil samples, it was weakly alkaline. The top layer of all the soils significantly differed from the lower one by the higher alkalinity promoting the deposition of heavy metals there. As the content of Ni, Co, and Mn increased and exceeded the background concentrations, but did not reach the three-fold value of the maximum permissible concentrations, the activity of catalase was intensified. The stimulating effect of nickel on the catalase activity was mostly pronounced at the neutral soil reaction. The urease activity increased when heavy metals and oil products were present together in the concentrations above the background ones, but not higher than the three-fold maximal permissible concentrations for heavy metals and 0.3 mg/g for the content of oil products. The nitrifying activity was inhibited by oil hydrocarbons that were recorded in the soils in different amounts.

pH and Organic Carbon Dose Rates Control Microbially Driven Bioremediation Efficacy in Alkaline Bauxite Residue.

PubMed

Santini, Talitha C; Malcolm, Laura I; Tyson, Gene W; Warren, Lesley A

2016-10-18

Bioremediation of alkaline tailings, based on fermentative microbial metabolisms, is a novel strategy for achieving rapid pH neutralization and thus improving environmental outcomes associated with mining and refining activities. Laboratory-scale bioreactors containing bauxite residue (an alkaline, saline tailings material generated as a byproduct of alumina refining), to which a diverse microbial inoculum was added, were used in this study to identify key factors (pH, salinity, organic carbon supply) controlling the rates and extent of microbially driven pH neutralization (bioremediation) in alkaline tailings. Initial tailings pH and organic carbon dose rates both significantly affected bioremediation extent and efficiency with lower minimum pHs and higher extents of pH neutralization occurring under low initial pH or high organic carbon conditions. Rates of pH neutralization (up to 0.13 mM H + produced per day with pH decreasing from 9.5 to ≤6.5 in three days) were significantly higher in low initial pH treatments. Representatives of the Bacillaceae and Enterobacteriaceae, which contain many known facultative anaerobes and fermenters, were identified as key contributors to 2,3-butanediol and/or mixed acid fermentation as the major mechanism(s) of pH neutralization. Initial pH and salinity significantly influenced microbial community successional trajectories, and microbial community structure was significantly related to markers of fermentation activity. This study provides the first experimental demonstration of bioremediation in bauxite residue, identifying pH and organic carbon dose rates as key controls on bioremediation efficacy, and will enable future development of bioreactor technologies at full field scale.

Automated image-based assay for evaluation of HIV neutralization and cell-to-cell fusion inhibition.

PubMed

Sheik-Khalil, Enas; Bray, Mark-Anthony; Özkaya Şahin, Gülsen; Scarlatti, Gabriella; Jansson, Marianne; Carpenter, Anne E; Fenyö, Eva Maria

2014-08-30

Standardized techniques to detect HIV-neutralizing antibody responses are of great importance in the search for an HIV vaccine. Here, we present a high-throughput, high-content automated plaque reduction (APR) assay based on automated microscopy and image analysis that allows evaluation of neutralization and inhibition of cell-cell fusion within the same assay. Neutralization of virus particles is measured as a reduction in the number of fluorescent plaques, and inhibition of cell-cell fusion as a reduction in plaque area. We found neutralization strength to be a significant factor in the ability of virus to form syncytia. Further, we introduce the inhibitory concentration of plaque area reduction (ICpar) as an additional measure of antiviral activity, i.e. fusion inhibition. We present an automated image based high-throughput, high-content HIV plaque reduction assay. This allows, for the first time, simultaneous evaluation of neutralization and inhibition of cell-cell fusion within the same assay, by quantifying the reduction in number of plaques and mean plaque area, respectively. Inhibition of cell-to-cell fusion requires higher quantities of inhibitory reagent than inhibition of virus neutralization.

Endotoxin Neutralization as a Biomonitor for Inflammatory Bowel Disease

PubMed Central

Champion, Keith; Chiu, Laura; Ferbas, John; Pepe, Michael

2013-01-01

Gram-negative bacterial endotoxin is a potent immunostimulant implicated in the development and/or progression of a variety of diseases. The mammalian immune system has both innate and adaptive immune responses to neutralize endotoxin. In this study, a system was developed to monitor bacterial exposure by measuring the extent and nature of endotoxin neutralization in plasma. In control patients, females had higher levels of endotoxin neutralization than males, mirroring clinical outcomes from bacterial infection and sepsis. In addition to the total amount of neutralization, we used inactivation techniques to elucidate the nature of this activity and develop a system to compare early and late immune responses. Using this method to monitor patients with inflammatory bowel disease, we found a more robust total response that relies more on long-term, adaptive components of the immune system and less on early, innate components. Our results indicate that endotoxin neutralization is a valuable method to discern inflammatory bowel disease patients from a control population. Additionally, the nature of neutralization may be valuable in monitoring disease severity and/or the role of medication. PMID:23826338

Recombinant TNF-binding protein from variola virus as a novel potential TNF antagonist.

PubMed

Gileva, I P; Nepomnyashchikh, T S; Ryazankin, I A; Shchelkunov, S N

2009-12-01

Gel-filtration chromatographic separation of the lysate of Sf21 insect cells infected with recombinant baculovirus BVi67 containing the gene for TNF-binding protein (CrmB) of variola virus (VARV) revealed that hTNF-cytotoxicity neutralization activity is associated with a fraction corresponding mainly to high molecular weight proteins (above 500 kDa) and less with fractions corresponding to proteins of 270 or 90 kDa. The recombinant VARV-CrmB protein has been purified by affinity chromatography. Difference in the experimentally determined and estimated (according to amino acid composition) VARV-CrmB molecular weight is due to glycosylation of the recombinant protein expressed in the insect cells. VARV-CrmB neutralizes in vitro the cytotoxic effect of hTNF and hLTalpha, and its TNF-neutralizing activity is two to three orders of magnitude higher compared to the analogous effects of type I and II soluble TNF receptors, comparable with the activity of mAb MAK195, and somewhat lower than the effect of the commercial drug Remicade.

Nickel-based electrodeposits as potential cathode catalysts for hydrogen production by microbial electrolysis

NASA Astrophysics Data System (ADS)

Mitov, M.; Chorbadzhiyska, E.; Nalbandian, L.; Hubenova, Y.

2017-07-01

The development of cost-effective cathodes, operating at neutral pH and ambient temperatures, is a crucial challenge for the practical application of microbial electrolysis cell (MEC) technology. In this study, NiW and NiMo co-deposits produced by electroplating on Ni-foam are explored as cathodes in MEC. The fabricated electrodes exhibit higher corrosion stability and enhanced electrocatalytic activity towards hydrogen evolution reaction in neutral electrolyte compared to the bare Ni-foam. NiW/Ni-foam electrodes possess six times higher intrinsic catalytic activity, estimated from data obtained by linear voltammetry and chronoamperometry. The newly developed electrodes are applied as cathodes in single-chamber membrane-free MEC reactors, inoculated with wastewater and activated sludge from a municipal wastewater treatment plant. Cathodic hydrogen recovery of 79% and 89% by using NiW and NiMo cathodes, respectively, is achieved at applied voltage of 0.6 V. The obtained results reveal potential for practical application of used catalysts in MEC.

How should I decide? The neural correlates of everyday moral reasoning.

PubMed

Sommer, Monika; Rothmayr, Christoph; Döhnel, Katrin; Meinhardt, Jörg; Schwerdtner, Johannes; Sodian, Beate; Hajak, Göran

2010-06-01

The present fMRI study is the first that investigates everyday moral conflict situations in which a moral standard clashes with a personal desire. In such situations people have to decide between a morally guided and a hedonistic behaviour. Twelve healthy subjects were presented with verbal stories describing conflicts with either moral or neutral content. The moral stories described conflicts requiring a decision between a personal desire and a conflicting moral standard, whereas the neutral conflicts required a decision between two conflicting personal desires. When compared to neutral conflicts, moral conflicts elicited higher activity in a wide spread neural network including the medial frontal cortex, the temporal cortex and the temporo-parietal junction and the posterior cingulate cortex. Further analyses of the moral conflicts revealed that hedonistic decisions in contrast to morally guided decisions were associated with significantly higher rankings of uncertainty and unpleasant emotions and induced significant more activation in the amygdala/parahippocampal region. The present results generalise findings on the neuroscience of moral understanding by extending it to everyday moral decisions. Furthermore, the results show that the amydala region plays a central role in the processing of negative emotional consequences associated with immoral decisions. Copyright 2010 Elsevier Ltd. All rights reserved.

Induction of human immunodeficiency virus neutralizing antibodies using fusion complexes.

PubMed

Zipeto, Donato; Matucci, Andrea; Ripamonti, Chiara; Scarlatti, Gabriella; Rossolillo, Paola; Turci, Marco; Sartoris, Silvia; Tridente, Giuseppe; Bertazzoni, Umberto

2006-05-01

Human immunodeficiency virus-1 (HIV-1) infects cells by membrane fusion that is mediated by the envelope proteins gp120/gp41 and the cellular receptors CD4 and CCR5. During this process, some conserved viral epitopes are temporarily exposed and may induce a neutralizing antibody response when fixed in the fusogenic conformation. These transient structures are conserved and may be effective antigens for use in an anti-HIV-1 vaccine. In this study we tested different conditions of preparation of fusion complexes inducing neutralizing antibodies against both R5 and X4 tropic HIV-1 strains. Cell lines expressing HIV-1 gp120/gp41 and CD4-CCR5 were prepared and conditions for producing fusion complexes were tested. Complexes produced at different temperature and fixative combinations were used to immunize mice. Results indicated that (a) fusion complexes prepared at either 21 degrees C, 30 degrees C or 37 degrees C were immunogenic and induced neutralizing antibodies against both R5 and X4 HIV-1 heterologous isolates; (b) after extensive purification of antibodies there was no cytotoxic effect; (c) complexes prepared at 37 degrees C were more immunogenic and induced higher titers of neutralizing antibodies than complexes prepared at either 21 degrees C or 30 degrees C; (d) the fixative used did not affect the titer of neutralizing antibodies except for glutaraldehyde which was ineffective; (e) the neutralizing activity was retained after CD4-CCR5 antibody removal. The production of higher titers of neutralizing antibody with fusion complexes prepared at 37 degrees C, as compared to lower temperatures, may be related to the induction of antibodies against many different conformation intermediates that subsequently act synergistically at different steps in the fusion process.

Growth-suppressing and algicidal properties of an extract from Arundo donax, an invasive riparian plant, against Prymnesium parvum, an invasive harmful alga.

PubMed

Patiño, Reynaldo; Rashel, Rakib H; Rubio, Amede; Longing, Scott

2018-01-01

This study examined the ability of acidic and neutral/alkaline fractions of a methanolic extract from giant reed (Arundo donax) and of two of its constituents, gramine and skatole, to inhibit growth of the ichthyotoxic golden alga (Prymnesium parvum) in batch culture. For this study, growth suppression was defined as inhibition of maximum cell density, algicidal activity as early occurrence of negative growth, and algistatic activity as lack of net growth. The acidic fraction did not affect algal growth. The neutral/alkaline fraction showed growth-suppressing and algicidal activities but no signs of algistatic activity - namely, cells in cultures surviving a partial-algicidal exposure concentration (causing transient negative growth) were later able to initiate positive growth but at higher concentrations, algicidal activity was full and irreversible. Gramine suppressed growth more effectively than skatole and at the highest concentration tested, gramine also showed partial-algicidal and algistatic activity. While the partial-algicidal activities of the neutral/alkaline fraction and of gramine were short-lived (≤6days) and thus may share similar mechanisms, algistatic activity was unique to gramine and persisted for >3 weeks. Given gramine's reported concentration in the neutral/alkaline fraction, its corresponding level of algicidal activity is much lower than the fraction's suggesting the latter contains additional potent algicides. Inhibition of maximum cell density by all test compounds was associated with reductions in exponential growth rate, and in the case of the neutral/alkaline fraction and gramine also reductions in early (pre-exponential) growth. These results indicate that giant reed is a potential source of natural products to control golden alga blooms. Giant reed is an invasive species in North America, thus also providing incentive for research into strategies to couple management efforts for both species. Published by Elsevier B.V.

Growth-suppressing and algicidal properties of an extract from Arundo donax, an invasive riparian plant, against Prymnesium parvum, an invasive harmful alga

USGS Publications Warehouse

Patino, Reynaldo; Rashel, Rakib H.; Rubio, Amede; Longing, Scott

2018-01-01

This study examined the ability of acidic and neutral/alkaline fractions of a methanolic extract from giant reed (Arundo donax) and of two of its constituents, gramine and skatole, to inhibit growth of the ichthyotoxic golden alga (Prymnesium parvum) in batch culture. For this study, growth suppression was defined as inhibition of maximum cell density, algicidal activity as early occurrence of negative growth, and algistatic activity as lack of net growth. The acidic fraction did not affect algal growth. The neutral/alkaline fraction showed growth-suppressing and algicidal activities but no signs of algistatic activity – namely, cells in cultures surviving a partial-algicidal exposure concentration (causing transient negative growth) were later able to initiate positive growth but at higher concentrations, algicidal activity was full and irreversible. Gramine suppressed growth more effectively than skatole and at the highest concentration tested, gramine also showed partial-algicidal and algistatic activity. While the partial-algicidal activities of the neutral/alkaline fraction and of gramine were short-lived (≤6 days) and thus may share similar mechanisms, algistatic activity was unique to gramine and persisted for >3 weeks. Given gramine’s reported concentration in the neutral/alkaline fraction, its corresponding level of algicidal activity is much lower than the fraction’s suggesting the latter contains additional potent algicides. Inhibition of maximum cell density by all test compounds was associated with reductions in exponential growth rate, and in the case of the neutral/alkaline fraction and gramine also reductions in early (pre-exponential) growth. These results indicate that giant reed is a potential source of natural products to control golden alga blooms. Giant reed is an invasive species in North America, thus also providing incentive for research into strategies to couple management efforts for both species.

Studies on ocular and parenteral application potentials of azithromycin- loaded anionic, cationic and neutral-charged emulsions.

PubMed

Tamilvanan, Shunmugaperumal; Khanum, Ramona; Senthilkumar, Sudalimuthu Ramachandran; Muthuraman, Marimuthu; Rajasekharan, Thenrajan

2013-10-01

Ocular and parenteral application potentials of azithromycin-containing, non-phospholipid-based cationic nanosized emulsion in comparison to the phospholipid-based anionic and neutral-charged nanosized emulsions were investigated. Various physical, chemical, nonclinical toxicity and antimicrobial activity studies (mean droplet diameter, surface charge, creaming index, entrapment efficiency, accelerated, long-term and freeze-thaw cycling stabilities, TLC study, modified hen's egg chorioallantoic membrane (HET-CAM) test, in vitro hemolysis test, in vitro and in vivo myotoxicity, and in vitro antimicrobial activity) were conducted for assessing the potentials of these three types of emulsions. Following autoclave sterilization, all of these emulsions exhibited a nanometer range mean particle diameter (200 ± 29 to 434 ± 13 nm). While the anionic and cationic emulsions did show high negative (-34.2 ± 1.23 mV) and positive zeta potential (42.6 ± 1.45 mV) values, the neutral-charged emulsion did not. Even with 5 freeze-thaw cycles, the cationic emulsion remained stable whereas other two emulsions underwent phase-separation. The hen's egg chorioallantoic membrane test revealed an irritation score value that was higher for the anionic emulsion than for cationic or neutral-charged emulsion. A significantly higher % hemolysis value was also noticed for the anionic emulsion when compared to the % hemolysis value of cationic emulsion (ANOVA, P ‹ 0.05). However, all of the emulsions showed a lesser intracellular creatine kinase (CK) release/plasma CK level in comparison to the positive control (phenytoin) indicating their lesser myotoxicity at the injection site . When compared to anionic and neutral-charged emulsions, the possible controlled drug release from cationic emulsion delayed the in vitro antimicrobial action against H.influenzae and S.pneumoniae.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder.

PubMed

Hassel, Stefanie; Almeida, Jorge R; Frank, Ellen; Versace, Amelia; Nau, Sharon A; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2009-11-01

The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Small sample size of predominantly medicated BD individuals. This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

A case study of the thermospheric neutral wind response to geomagnetic storm

NASA Astrophysics Data System (ADS)

Jiang, Guoying; Zhang, Shunrong; Wang, Wenbin; Yuan, Wei; Wu, Qian; Xu, Jiyao

A minor geomagnetic storm (Kp=5) occurred on March 27-28, 2012. The response of the thermospheric neutral wind at ~ 250 km to this storm was investigated by the 630.0 nm nightglow measurements of Fabry-Perot interferometers (FPIs) over Xinglong (geographic location: 40.2N, 117.4E; geomagnetic location: 29.8N, 193.2E) and Millstone Hill (geographic location: 42.6N, 71.5W; geomagnetic location: 53.1N, 65.1W). Our results show that the minor storm on March 27-28, 2012 obviously effected on the thermospheric neutral winds over Xinglong and Millstone Hill, especially Millstone Hill had larger response because of its higher geomagnetic latitude. Another interesting result is that a small variation in geomagnetic activity (Kp=2.7) could enough introduce a clear disturbance in the nighttime thermospheric neutral wind over Millstone hill. NCAR-TIME-GCM (National Center for Atmospheric Research-Thermosphere Ionosphere Mesosphere Electrodynamics-General Circulation Model) was employed to study the evolution and mechanism of the thermospheric neutral wind response.

A comparative study of the antacid effect of raw spinach juice and spinach extract in an artificial stomach model.

PubMed

Panda, Vandana Sanjeev; Shinde, Priyanka Mangesh

2016-12-01

BackgroundSpinacia oleracea known as spinach is a green-leafy vegetable consumed by people across the globe. It is reported to possess potent medicinal properties by virtue of its numerous antioxidant phytoconstituents, together termed as the natural antioxidant mixture (NAO). The present study compares the antacid effect of raw spinach juice with an antioxidant-rich methanolic extract of spinach (NAOE) in an artificial stomach model. MethodsThe pH of NAOE at various concentrations (50, 100 and 200 mg/mL) and its neutralizing effect on artificial gastric acid was determined and compared with that of raw spinach juice, water, the active control sodium bicarbonate (SB) and a marketed antacid preparation ENO. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization of artificial gastric acid for the test compounds. The neutralizing capacity of test compounds was determined in vitro using the classical titration method of Fordtran. Results NAOE (50, 100 and 200 mg/mL), spinach juice, SB and ENO showed significantly better acid-neutralizing effect, consistent duration of neutralization and higher antacid capacity when compared with water. Highest antacid activity was demonstrated by ENO and SB followed by spinach juice and NAOE200. Spinach juice exhibited an effect comparable to NAOE (200 mg/mL). ConclusionsThus, it may be concluded that spinach displays significant antacid activity be it in the raw juice form or as an extract in methanol.

Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children.

PubMed Central

Broliden, K; Sievers, E; Tovo, P A; Moschese, V; Scarlatti, G; Broliden, P A; Fundaro, C; Rossi, P

1993-01-01

The prognostic and protective role of antibodies mediating cellular cytotoxicity (ADCC) and neutralization was evaluated in sera of HIV-1-infected mothers and their consecutively followed children. The presence and titres of ADCC mediating and/or neutralizing antibodies in maternal sera did not predict HIV-1 infection in their respective children. No significant difference in the sera from the children was seen when comparing the presence of neutralizing antibodies between the uninfected and infected children. Stratification of the infected group according to clinical status revealed differences. Only one of 24 AIDS patients had a high neutralizing titre against IIIB. Four patients had a very low titre and the remaining had no detectable neutralizing antibodies at all. In contrast, 10/17 infected non-AIDS children had neutralizing antibodies. Similarly, no significant difference was seen when comparing the presence of ADCC-mediating antibodies between the uninfected and the infected group of children. However, a significantly higher frequency of ADCC was seen in the seropositive non-AIDS children compared with the AIDS children. This study clearly shows that the presence of antibodies mediating ADCC and neutralization in infected children, 0-2 years old, is associated with a better clinical status and delayed disease progression. PMID:8324904

Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes.

PubMed

Vaidya, Sunil R; Dvivedi, Garima M; Jadhav, Santoshkumar M

2016-01-01

The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.

Crystal engineering of a zwitterionic drug to neutral cocrystals: a general solution for floxacins.

PubMed

Gunnam, Anilkumar; Suresh, Kuthuru; Ganduri, Ramesh; Nangia, Ashwini

2016-10-18

The transformation of zwitterionic Sparfloxacin (SPX) to the neutral form is achieved by cocrystallization. Neutral forms of drugs are important for higher membrane permeability, while zwitterions are more soluble in water. The twin advantages of higher solubility/dissolution rate and good stability of neutral SPX are achieved in a molecular cocrystal compared to its zwitterionic SPX hydrate. The amine-phenol supramolecular synthon drives cocrystal formation, with the paraben ester acting as a "proton migrator" for the ionic to neutral transformation.

Significant advantages of sulfur-doped graphene in neutral media as electrocatalyst for oxygen reduction comparing with Pt/C

NASA Astrophysics Data System (ADS)

Shi, Xinxin; Zhang, Jiaona; Huang, Tinglin

2018-02-01

Sulfur-doped graphene (SDG) has been found to be an efficient electrocatalyst for oxygen reduction reaction. However, previous studies on the catalytic activity of SDG have been mainly confined to O2-saturated alkaline media which is a typical alkaline fuel cell environment. Air-cathode microbial fuel cells (ACMFCs), as a novel energy conversion and wastewater treatment technology, use the oxygen from air as cathodic reactant in neutral media with low concentration of O2. Thus, it is meaningful to explore the catalytic performance of SDG in such ACMFC environment. The result showed that in ACMFC environment, the peak current density of SDG in CV test was surprisingly 4.5 times higher than that of Pt/C, indicating a much stronger catalytic activity of SDG. Moreover, SDG exhibited a stronger tolerance against the crossover of glucose (a typical anodic fuel in ACMFC) and better stability than Pt/C in neutral media.

Work postures and neck-shoulder pain among orchestra musicians.

PubMed

Nyman, Teresia; Wiktorin, Christina; Mulder, Marie; Johansson, Yvonne Liljeholm

2007-05-01

The purpose of the present study was to identify associations between a work posture with elevated arm position, duration of active playing time, and neck-shoulder pain among orchestra musicians. In this study, with a cross-sectional study design, a total of 235 subjects from 12 Swedish orchestras were categorized into four exposure groups according to arm position and duration of active playing time. Logistic regression analysis was used to calculate odds ratios (OR) for neck-shoulder pain in the four exposure groups. A higher prevalence of neck-shoulder pain were found in the groups "elevated arm position, <2 hr per workday" [OR 4.15 (1.30-13.22)], and "elevated arm position, >3 hr per workday" [OR 5.35 (1.96-14.62)] compared to the group "neutral arm position, <2 hr per workday". Musicians working in an elevated arm position (e.g., violinists, violists, flutists, and trumpet players) had a higher prevalence of neck-shoulder pain than those working in a more neutral position.

Impact of emotional salience on episodic memory in attention-deficit/hyperactivity disorder: a functional magnetic resonance imaging study.

PubMed

Krauel, Kerstin; Duzel, Emrah; Hinrichs, Hermann; Santel, Stephanie; Rellum, Thomas; Baving, Lioba

2007-06-15

Patients with attention-deficit/hyperactivity disorder (ADHD) show episodic memory deficits especially in complex memory tasks. We investigated the neural correlates of memory formation in ADHD and their modulation by stimulus salience. We recorded event-related functional magnetic resonance imaging during an episodic memory paradigm with neutral and emotional pictures in 12 male ADHD subjects and 12 healthy adolescents. Emotional salience did significantly augment memory performance in ADHD patients. Successful encoding of neutral pictures was associated with activation of the anterior cingulate cortex (ACC) in healthy adolescents but with activation of the superior parietal lobe (SPL) and precuneus in ADHD patients. Successful encoding of emotional pictures was associated with prefrontal and inferior temporal cortex activation in both groups. Healthy adolescents, moreover, showed deactivation in the inferior parietal lobe. From a pathophysiological point of view, the most striking functional differences between healthy adolescents and ADHD patients were in the ACC and SPL. We suggest that increased SPL activation in ADHD reflected attentional compensation for low ACC activation during the encoding of neutral pictures. The higher salience of emotional stimuli, in contrast, regulated the interplay between ACC and SPL in conjunction with improving memory to the level of healthy adolescents.

Improved volatile fatty acids anaerobic production from waste activated sludge by pH regulation: Alkaline or neutral pH?

PubMed

Ma, Huijun; Chen, Xingchun; Liu, He; Liu, Hongbo; Fu, Bo

2016-02-01

In this study, the anaerobic fermentation was carried out for volatile fatty acids (VFAs) production at different pH (between 7.0 and 10.0) conditions with untreated sludge and heat-alkaline pretreated waste activated sludge. In the fermentation with untreated sludge, the extent of hydrolysis of organic matters and extent of acidification at alkaline pH are 54.37% and 30.37%, respectively, resulting in the highest VFAs yield at 235.46mg COD/gVS of three pH conditions. In the fermentation with heat-alkaline pretreated sludge, the acidification rate and VFAs yield at neutral pH are 30.98% and 240.14mg COD/gVS, respectively, which are higher than that at other pH conditions. With the glucose or bovine serum albumin as substrate for VFAs production, the neutral pH showed a higher VFAs concentration than the alkaline pH condition. The results of terminal restriction fragment length polymorphism (T-RFLP) analysis indicated that the alkaline pH caused low microbial richness. Based on the results in this study, we demonstrated that the alkaline pH is favor of hydrolysis of organic matter in sludge while neutral pH improved the acidogenesis for the VFAs production from sludge. Our finding is obvious different to the previous research and helpful for the understanding of how heat-alkaline pretreatment and alkaline fermentation influence the VFAs production, and beneficial to the development of VFAs production process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improving the neutral phytase activity from Bacillus amyloliquefaciens DSM 1061 by site-directed mutagenesis.

PubMed

Xu, Wei; Shao, Rong; Wang, Zupeng; Yan, Xiuhua

2015-03-01

Neutral phytase is used as a feed additive for degradation of anti-nutritional phytate in aquatic feed industry. Site-directed mutagenesis of Bacillus amyloliquefaciens DSM 1061 phytase was performed with an aim to increase its activity. Mutation residues were chosen based on multiple sequence alignments and structure analysis of neutral phytsaes from different microorganisms. The mutation sites on surface (D148E, S197E and N156E) and around the active site (D52E) of phytase were selected. Analysis of the phytase variants showed that the specific activities of mutants D148E and S197E remarkably increased by about 35 and 13% over a temperature range of 40-75 °C at pH 7.0, respectively. The k cat of mutants D148E and S197E were 1.50 and 1.25 times than that of the wild-type phytase, respectively. Both D148E and S197E showed much higher thermostability than that of the wild-type phytase. However, mutants N156E and D52E led to significant loss of specific activity of the enzyme. Structural analysis revealed that these mutations may affect conformation of the active site of phytase. The present mutant phytases D148E and S197E with increased activities and thermostabilities have application potential as additives in aquaculture feed.

VISIONS: Remote Observations of a Spatially-Structured Filamentary Source of Energetic Neutral Atoms near the Polar Cap Boundary During an Auroral Substorm

NASA Technical Reports Server (NTRS)

Collier, Michael R.; Chornay, D.; Clemmons, J.; Keller, J. W.; Klenzing, J.; Kujawski, J.; McLain, J.; Pfaff, R.; Rowland, D.; Zettergren, M.

2015-01-01

We report initial results from the VISualizing Ion Outflow via Neutral atom imaging during a Substorm (VISIONS) rocket that flew through and near several regions of enhanced auroral activity and also sensed regions of ion outflow both remotely and directly. The observed neutral atom fluxes were largest at the lower energies and generally higher in the auroral zone than in the polar cap. In this paper, we focus on data from the latter half of the VISIONS trajectory when the rocket traversed the polar cap region. During this period, many of the energetic neutral atom spectra show a peak at 100 electronvolts. Spectra with peaks around 100 electronvolts are also observed in the Electrostatic Ion Analyzer (EIA) data consistent with these ions comprising the source population for the energetic neutral atoms. The EIA observations of this low energy population extend only over a few tens of kilometers. Furthermore, the directionality of the arriving energetic neutral atoms is consistent with either this spatially localized source of energetic ions extending from as low as about 300 kilometers up to above 600 kilometers or a larger source of energetic ions to the southwest.

Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2008-08-15

To characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups. PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of pseudobulbar affect.

Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of Autologous Tier 2 Neutralizing Antibodies.

PubMed

Feng, Yu; Tran, Karen; Bale, Shridhar; Kumar, Shailendra; Guenaga, Javier; Wilson, Richard; de Val, Natalia; Arendt, Heather; DeStefano, Joanne; Ward, Andrew B; Wyatt, Richard T

2016-08-01

In the context of HIV vaccine design and development, HIV-1 spike mimetics displaying a range of stabilities were evaluated to determine whether more stable, well-ordered trimers would more efficiently elicit neutralizing antibodies. To begin, in vitro analysis of trimers derived from the cysteine-stabilized SOSIP platform or the uncleaved, covalently linked NFL platform were evaluated. These native-like trimers, derived from HIV subtypes A, B, and C, displayed a range of thermostabilities, and were "stress-tested" at varying temperatures as a prelude to in vivo immunogenicity. Analysis was performed both in the absence and in the presence of two different adjuvants. Since partial trimer degradation was detected at 37°C before or after formulation with adjuvant, we sought to remedy such an undesirable outcome. Cross-linking (fixing) of the well-ordered trimers with glutaraldehyde increased overall thermostability, maintenance of well-ordered trimer integrity without or with adjuvant, and increased resistance to solid phase-associated trimer unfolding. Immunization of unfixed and fixed well-ordered trimers into animals revealed that the elicited tier 2 autologous neutralizing activity correlated with overall trimer thermostability, or melting temperature (Tm). Glutaraldehyde fixation also led to higher tier 2 autologous neutralization titers. These results link retention of trimer quaternary packing with elicitation of tier 2 autologous neutralizing activity, providing important insights for HIV-1 vaccine design.

Neutralization of B. anthracis toxins during ex vivo phagocytosis.

PubMed

Tarasenko, Olga; Scott, Ashley; Jones, April; Soderberg, Lee; Alusta, Pierre

2013-07-01

Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.

Longitudinal Analysis of Early HIV-1-Specific Neutralizing Activity in an Elite Neutralizer and in Five Patients Who Developed Cross-Reactive Neutralizing Activity

PubMed Central

Euler, Zelda; van den Kerkhof, Tom L. G. M.; van Gils, Marit J.; Burger, Judith A.; Edo-Matas, Diana; Phung, Pham; Wrin, Terri

2012-01-01

We previously established that at 3 years postseroconversion, ∼30% of HIV-infected individuals have cross-reactive neutralizing activity (CrNA) in their sera. Here we studied the kinetics with which CrNA develops and how these relate to the development of autologous neutralizing activity as well as viral escape and diversification. For this purpose, sera from five individuals with CrNA and one elite neutralizer that were obtained at three monthly intervals in the first year after seroconversion and at multiple intervals over the disease course were tested for neutralizing activity against an established multiclade panel of six viruses. The same serum samples, as well as sera from three individuals who lacked CrNA, were tested for their neutralizing activities against autologous clonal HIV-1 variants from multiple time points covering the disease course from seroconversion onward. The elite neutralizer already had CrNA at 9.8 months postseroconversion, in contrast with the findings for the other five patients, in whom CrNA was first detected at 20 to 35 months postseroconversion and peaked around 35 months postseroconversion. In all patients, CrNA coincided with neutralizing activity against autologous viruses that were isolated <12 months postseroconversion, while viruses from later time points had already escaped autologous neutralizing activity. Also, the peak in gp160 sequence diversity coincided with the peak of CrNA titers. Individuals who lacked CrNA had lower peak autologous neutralizing titers, viral escape, and sequence diversity than individuals with CrNA. A better understanding of the underlying factors that determine the presence of CrNA or even an elite neutralizer phenotype may aid in the design of an HIV-1 vaccine. PMID:22156522

Inferred flows of electric currents in solar active regions

NASA Technical Reports Server (NTRS)

Ding, Y. J.; Hong, Q. F.; Hagyard, M. J.; Deloach, A. C.

1985-01-01

Techniques to identify sources of major current systems in active regions and their channels of flow are explored. Measured photospheric vector magnetic fields together with high resolution white light and H-alpha photographs provide the data base to derive the current systems in the photosphere and chromosphere of a solar active region. Simple mathematical constructions of active region fields and currents are used to interpret these data under the assumptions that the fields in the lower atmosphere (below 200 km) may not be force free but those in the chromosphere and higher are. The results obtained for the complex active region AR 2372 are: (1) Spots exhibiting significant spiral structure in the penumbral filaments were the source of vertical currents at the photospheric surface; (2) Magnetic neutral lines where the transverse magnetic field was strongly sheared were channels along which a strong current system flowed; (3) The inferred current systems produced a neutral sheet and oppositely-flowing currents in the area of the magnetic delta configuration that was the site of flaring.

Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes

PubMed Central

Vaidya, Sunil R.; Dvivedi, Garima M.; Jadhav, Santoshkumar M.

2016-01-01

Background & objectives: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. Methods: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. Results: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Interpretation & conclusions: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. PMID:26997012

Reaching Higher Gamma in Ultracold Neutral Plasmas Through Disorder-Induced Heating Control

DTIC Science & Technology

2016-06-27

shielding ,” Phys. Rev. E 87, 033101 (2013) 4 Sequential ionization of ultracold plasma ions A simulation published in 2007 by Michael Murillo showed...AFRL-AFOSR-VA-TR-2017-0031 Reaching higher Gamma in ultracold neutral plasmas through disorder-induced heating control Scott Bergeson BRIGHAM YOUNG...TYPE Final Report 3. DATES COVERED (From - To) 01 June 2012 - 31 May 2016 4. TITLE AND SUBTITLE Reaching higher Gamma in ultracold neutral plasmas

Efficient neutralization of primary isolates by the plasma from HIV-1 infected Indian children.

PubMed

Prakash, S S; Chaudhary, Alok Kumar; Lodha, Rakesh; Kabra, S K; Vajpayee, Madhu; Hazarika, Anjali; Bagga, Barun; Luthra, Kalpana

2011-10-01

We tested the plasma of 51 HIV-1-infected children (23 naïve and 28 ART treated) for neutralization against five primary isolates (PIs) generated from adult Indian HIV-1-infected patients. The plasma exhibited neutralization potential with significantly higher neutralizing antibody titers in ART-treated children than naïve children against three out of five PIs (p<0.0001). Further, in treated children, neutralizing antibody titers were higher in those children with suppressed viremia (<1000 RNA copies/mL) than non-suppressors against two of the three PIs. We report here for the first time the neutralization potential of the plasma of HIV-1-infected Indian children.

Measuring positive and negative affect in the voiced sounds of African elephants (Loxodonta africana).

PubMed

Soltis, Joseph; Blowers, Tracy E; Savage, Anne

2011-02-01

As in other mammals, there is evidence that the African elephant voice reflects affect intensity, but it is less clear if positive and negative affective states are differentially reflected in the voice. An acoustic comparison was made between African elephant "rumble" vocalizations produced in negative social contexts (dominance interactions), neutral social contexts (minimal social activity), and positive social contexts (affiliative interactions) by four adult females housed at Disney's Animal Kingdom®. Rumbles produced in the negative social context exhibited higher and more variable fundamental frequencies (F(0)) and amplitudes, longer durations, increased voice roughness, and higher first formant locations (F1), compared to the neutral social context. Rumbles produced in the positive social context exhibited similar shifts in most variables (F(0 )variation, amplitude, amplitude variation, duration, and F1), but the magnitude of response was generally less than that observed in the negative context. Voice roughness and F(0) observed in the positive social context remained similar to that observed in the neutral context. These results are most consistent with the vocal expression of affect intensity, in which the negative social context elicited higher intensity levels than the positive context, but differential vocal expression of positive and negative affect cannot be ruled out.

Perfluoroalkyl and polyfluoroalkyl substances in the lower atmosphere and surface waters of the Chinese Bohai Sea, Yellow Sea, and Yangtze River estuary.

PubMed

Zhao, Zhen; Tang, Jianhui; Mi, Lijie; Tian, Chongguo; Zhong, Guangcai; Zhang, Gan; Wang, Shaorui; Li, Qilu; Ebinghaus, Ralf; Xie, Zhiyong; Sun, Hongwen

2017-12-01

Polyfluoroalkyl and perfluoroalkyl substances (PFASs), in the forms of neutral polyfluoroalkyl substances in the gas phase of air and ionic perfluoroalkyl substances in the dissolved phase of surface water, were investigated during a sampling campaign in the Bohai Sea, Yellow Sea, and Yangtze River estuary in May 2012. In the gas phase, the concentrations of neutral ∑PFASs were within the range of 76-551pg/m 3 . Higher concentrations were observed in the South Yellow Sea. 8:2 fluorotelomer alcohol (FTOH) was the predominant compound as it accounted for 92%-95% of neutral ∑PFASs in all air samples. Air mass backward trajectory analysis indicated that neutral ∑PFASs came mainly from the coast of the Yellow Sea, including the Shandong, Jiangsu, and Zhejiang provinces of China, and the coastal region of South Korea. The fluxes of gas phase dry deposition were simulated for neutral PFASs, and neutral ∑PFASs fluxes varied from 0.37 to 2.3pg/m 2 /s. In the dissolved phase of the surface water, concentrations of ionic ∑PFASs ranged from 1.6 to 118ng/L, with the Bohai Sea exhibiting higher concentrations than both the Yellow Sea and the Yangtze River estuary. Perfluorooctanoic acid (PFOA) was the predominant compound accounting for 51%-90% of the ionic ∑PFAS concentrations. Releases from industrial and domestic activities as well as the semiclosed geographical conditions increased the level of ionic ∑PFASs in the Bohai Sea. The spatial distributions of perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkane sulfonic acids (PFSAs) were different significantly. The Laizhou Bay was the major source region of PFCAs and the Yangtze River estuary was the major source of PFSAs. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

The Neurobiology of Self-Face Recognition in Depressed Adolescents with Low or High Suicidality

PubMed Central

Quevedo, Karina; Ng, Rowena; Scott, Hannah; Martin, Jodi; Smyda, Garry; Keener, Matt; Oppenheimer, Caroline W.

2017-01-01

This study sought to test whether the neurobiology of self-processing differentiated depressed adolescents with high suicidality from those with low suicidality and healthy controls (N=119, MAGE= 14.79, SD=1.64, Min=11.3, Max = 17.8). Participants completed a visual self-recognition task in the scanner during which they identified their own or an unfamiliar adolescent face across three emotional expressions (happy, neutral or sad). A 3 Group (HS, LS, HC) by two within subject factors [2 Self conditions (self, other) and 3 Emotions (happy, neutral, sad)] GLM yielded: 1) a main effect of Self condition with all participants showing higher activity in the right occipital, precuneus and fusiform during the self-versus other-face conditions; 2) a main effect of Group where all depressed youth showed higher dorsolateral prefrontal cortex activity than HC across all conditions, and with HS showing higher cuneus and occipital activity versus both LS and HC; and 3) a Group by Self by Emotion interaction with HS showing lower activity in both mid parietal, limbic and prefrontal areas in the Happy self versus other-face condition relative to the LS group, who in turn had less activity compared to HC youth. Covarying for depression severity replicated all results except the third finding; in this subsequent analysis, a Group by Self interaction showed that although HC had similar midline cortical structure (MCS) activity for all faces, LS showed higher MCS activity for the self vs. other faces while HS showed the opposite pattern. Results suggest that the neurophysiology of emotionally charged self-referential information can distinguish depressed, suicidal youth versus non-suicidal depressed and healthy adolescents. Neurophysiological differences and implications for the prediction of suicidality in youth are discussed. General Scientific Summary: Depressed adolescents with high suicidality show less activity in brain areas that support emotional experiences and self-awareness when identifying their own face, suggesting that abnormal self-processing may be associated with greater suicide risk. PMID:27618278

Occurrence of tetrodotoxin-binding high molecular weight substances in the body fluid of shore crab (Hemigrapsus sanguineus).

PubMed

Shiomi, K; Yamaguchi, S; Kikuchi, T; Yamamori, K; Matsui, T

1992-12-01

The shore crab (Hemigrapsus sanguineus) is highly resistant to tetrodotoxin (TTX) although it contains no detectable amount of TTX (less than 5 MU/g, where 1 MU is defined as the amount of TTX killing a 20 g mouse in 30 min). Its body fluid was examined for neutralizing effects against the lethal activity of TTX. When the mixture of the body fluid and TTX was injected i.p. into mice, the lethal activity of TTX was significantly reduced; 1 ml of the body fluid was evaluated to neutralize 3.6-4.0 MU of TTX. Higher neutralizing activity (7.2-12.5 MU/ml of the body fluid) was exhibited by i.v. administration of the body fluid into mice before or after i.p. challenge of TTX. The lethal effect of paralytic shellfish poisons was not counteracted by the body fluid. Analysis by gel filtration on Sepharose 6B revealed that the body fluid contained TTX-binding high mol. wt substances (> 2,000,000) responsible for the neutralizing activity of the body fluid against TTX, which accounts for the high resistibility of the crab to TTX. When the crude toxin extracted from the liver of puffer (Takifugu niphobles) was mixed with the body fluid and chromatographed on Sepharose 6B, almost pure TTX was obtained from the fractions containing the TTX-binding high mol. wt substances, suggesting that the TTX-binding high mol. wt substances could be useful in purification of TTX from biological samples.

Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents.

PubMed

Reis, R S; Dalle Molle, R; Machado, T D; Mucellini, A B; Rodrigues, D M; Bortoluzzi, A; Bigonha, S M; Toazza, R; Salum, G A; Minuzzi, L; Buchweitz, A; Franco, A R; Pelúzio, M C G; Manfro, G G; Silveira, P P

2016-03-15

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.

Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents

PubMed Central

Reis, R S; Dalle Molle, R; Machado, T D; Mucellini, A B; Rodrigues, D M; Bortoluzzi, A; Bigonha, S M; Toazza, R; Salum, G A; Minuzzi, L; Buchweitz, A; Franco, A R; Pelúzio, M C G; Manfro, G G; Silveira, P P

2016-01-01

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults. PMID:26978737

Temporal Co-Variation between Eye Lens Accommodation and Trapezius Muscle Activity during a Dynamic Near-Far Visual Task

PubMed Central

Zetterberg, Camilla; Richter, Hans O.; Forsman, Mikael

2015-01-01

Near work is associated with increased activity in the neck and shoulder muscles, but the underlying mechanism is still unknown. This study was designed to determine whether a dynamic change in focus, alternating between a nearby and a more distant visual target, produces a direct parallel change in trapezius muscle activity. Fourteen healthy controls and 12 patients with a history of visual and neck/shoulder symptoms performed a Near-Far visual task under three different viewing conditions; one neutral condition with no trial lenses, one condition with negative trial lenses to create increased accommodation, and one condition with positive trial lenses to create decreased accommodation. Eye lens accommodation and trapezius muscle activity were continuously recorded. The trapezius muscle activity was significantly higher during Near than during Far focusing periods for both groups within the neutral viewing condition, and there was a significant co-variation in time between accommodation and trapezius muscle activity within the neutral and positive viewing conditions for the control group. In conclusion, these results reveal a connection between Near focusing and increased muscle activity during dynamic changes in focus between a nearby and a far target. A direct link, from the accommodation/vergence system to the trapezius muscles cannot be ruled out, but the connection may also be explained by an increased need for eye-neck (head) stabilization when focusing on a nearby target as compared to a more distant target. PMID:25961299

Temporal Co-Variation between Eye Lens Accommodation and Trapezius Muscle Activity during a Dynamic Near-Far Visual Task.

PubMed

Zetterberg, Camilla; Richter, Hans O; Forsman, Mikael

2015-01-01

Near work is associated with increased activity in the neck and shoulder muscles, but the underlying mechanism is still unknown. This study was designed to determine whether a dynamic change in focus, alternating between a nearby and a more distant visual target, produces a direct parallel change in trapezius muscle activity. Fourteen healthy controls and 12 patients with a history of visual and neck/shoulder symptoms performed a Near-Far visual task under three different viewing conditions; one neutral condition with no trial lenses, one condition with negative trial lenses to create increased accommodation, and one condition with positive trial lenses to create decreased accommodation. Eye lens accommodation and trapezius muscle activity were continuously recorded. The trapezius muscle activity was significantly higher during Near than during Far focusing periods for both groups within the neutral viewing condition, and there was a significant co-variation in time between accommodation and trapezius muscle activity within the neutral and positive viewing conditions for the control group. In conclusion, these results reveal a connection between Near focusing and increased muscle activity during dynamic changes in focus between a nearby and a far target. A direct link, from the accommodation/vergence system to the trapezius muscles cannot be ruled out, but the connection may also be explained by an increased need for eye-neck (head) stabilization when focusing on a nearby target as compared to a more distant target.

HdeB chaperone activity is coupled to its intrinsic dynamic properties

PubMed Central

Ding, Jienv; Yang, Chengfeng; Niu, Xiaogang; Hu, Yunfei; Jin, Changwen

2015-01-01

Enteric bacteria encounter extreme acidity when passing through hosts’ stomach. Since the bacterial periplasmic space quickly equilibrates with outer environment, an efficient acid resistance mechanism is essential in preventing irreversible protein denaturation/aggregation and maintaining bacteria viability. HdeB, along with its homolog HdeA, was identified as a periplasmic acid-resistant chaperone. Both proteins exist as homodimers and share similar monomeric structures under neutral pH, while showing different dimeric packing interfaces. Previous investigations show that HdeA functions through an acid-induced dimer-to-monomer transition and partial unfolding at low pH (pH 2–3), resulting in exposure of hydrophobic surfaces that bind substrate proteins. In contrast, HdeB appears to have a much higher optimal activation pH (pH 4–5), under which condition the protein maintains a well-folded dimer and the mechanism for its chaperone activity remains elusive. Herein, we present an NMR study of HdeB to investigate its dynamic properties. Our results reveal that HdeB undergoes significant micro- to milli-second timescale conformational exchanges at neutral to near-neutral pH, under the later condition it exhibits optimal activity. The current study indicates that HdeB activation is coupled to its intrinsic dynamics instead of structural changes, and therefore its functional mechanism is apparently different from HdeA. PMID:26593705

Behavioral and neural indices of affective coloring for neutral social stimuli

PubMed Central

Schaefer, Stacey M; Lapate, Regina C; Schoen, Andrew J; Gresham, Lauren K; Mumford, Jeanette A; Davidson, Richard J

2018-01-01

Abstract Emotional processing often continues beyond the presentation of emotionally evocative stimuli, which can result in affective biasing or coloring of subsequently encountered events. Here, we describe neural correlates of affective coloring and examine how individual differences in affective style impact the magnitude of affective coloring. We conducted functional magnetic resonance imaging in 117 adults who passively viewed negative, neutral and positive pictures presented 2 s prior to neutral faces. Brain responses to neutral faces were modulated by the valence of preceding pictures, with greater activation for faces following negative (vs positive) pictures in the amygdala, dorsomedial and lateral prefrontal cortex, ventral visual cortices, posterior superior temporal sulcus, and angular gyrus. Three days after the magnetic resonance imaging scan, participants rated their memory and liking of previously encountered neutral faces. Individuals higher in trait positive affect and emotional reappraisal rated faces as more likable when preceded by emotionally arousing (negative or positive) pictures. In addition, greater amygdala responses to neutral faces preceded by positively valenced pictures were associated with greater memory for these faces 3 days later. Collectively, these results reveal individual differences in how emotions spill over onto the processing of unrelated social stimuli, resulting in persistent and affectively biased evaluations of such stimuli. PMID:29447377

HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced HIV-Specific CD4+ T Cell Responses

PubMed Central

Soghoian, Damien Z.; Lindqvist, Madelene; Ghebremichael, Musie; Donaghey, Faith; Carrington, Mary; Seaman, Michael S.; Kaufmann, Daniel E.; Walker, Bruce D.

2015-01-01

ABSTRACT Antigen-specific CD4+ T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+ T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+ T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+ T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4+ T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+ T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4+ T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+ T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+ T cells and, to a lesser extent, gp41-specific CD4+ T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies. IMPORTANCE One of the earliest discoveries related to CD4+ T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4+ T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+ T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4+ T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4+ T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4+ T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection. PMID:26656715

[Specific humoral immunity after single immunization with mumps vaccine: data of a 3-year follow-up].

PubMed

Otrashevskaia, A V; Bukin, E K; Krasil'nikov, I V; Ignat'ev, G M

2011-01-01

The level and spectrum of humoral specific immunity were studied in 60 volunteers immunized with Russian mumps vaccine. Specific IgG levels were measured by enzyme immunoassay (EIA) and neutralization test using the Leningrad-3 (L-3) mumps virus (MV) vaccine strain and 5 heterologous MV strains of various genotypes (A, B, C, D, and H). The maximum functional activity of antibodies was recorded at an average of 18 months postvaccination. Within 3 years after vaccination, starting at 6 months, specific IgG neutralized all 6 MV strains having varying activity in relation to the genotype. Neutralizing titers (NT) against the L-3 strain were 1.3-1.7-fold higher than those against heterologous MV strains throughout the follow-up. Despite a tendency towards lower specific IgG levels, within 3 years postvaccination, EIA IgG titers remained to be 2.5 -log, L-3 strain HT were -log, or more, and the titers against 5 heterologous MV strains were 2 -log2 or more in all the volunteers.

Trait anxiety impact on posterior activation asymmetries at rest and during evoked negative emotions: EEG investigation.

PubMed

Aftanas, Ljubomir I; Pavlov, Sergey V

2005-01-01

The main objective of the present investigation was to examine how high trait anxiety would influence cortical EEG asymmetries under non-emotional conditions and while experiencing negative emotions. The 62-channel EEG was recorded in control (n=21) and high anxiety (HA, n=18) non-patient individuals. Results showed that in HA subjects, the lowest level of arousal (eyes closed) was associated with stronger right-sided parieto-temporal theta-1 (4-6 Hz) and beta-1 (12-18 Hz) activity, whereas increased non-emotional arousal (eyes open, viewing neutral movie clip) was marked by persisting favored right hemisphere beta-1 activity. In turn, viewing aversive movie clip by the HA group led to significant lateralized decrease of the right parieto-temporal beta-1 power, which was initially higher in the emotionally neutral conditions. The EEG data suggests that asymmetrical parieto-temporal theta-1 and beta-1 EEG activity might be better interpreted in terms of Gray's BAS and BIS theory.

Inducing unconscious stress: Cardiovascular activity in response to subliminal presentation of threatening and neutral words.

PubMed

van der Ploeg, Melanie M; Brosschot, Jos F; Verkuil, Bart; Gillie, Brandon L; Williams, DeWayne P; Koenig, Julian; Vasey, Michael W; Thayer, Julian F

2017-10-01

Stress-related cognitive processes may occur outside of awareness, here referred to as unconscious stress, and affect one's physiological state. Evidence supporting this idea would provide necessary clarification of the relationship between psychological stress and cardiovascular (CV) health problems. We tested the hypothesis that increases in mean arterial pressure (MAP) and total peripheral resistance (TPR) and decreases in heart rate variability (HRV) would be larger when threatening stimuli are presented outside of awareness, or subliminally, compared with neutral stimuli. Additionally, it was expected that trait worry and resting HRV, as common risk factors for CV disease, would moderate the effect. We presented a subliminal semantic priming paradigm to college students that were randomly assigned to the threat (n = 56) or neutral condition (n = 60) and assessed changes from baseline of MAP, TPR, and HRV. Level of trait worry was assessed with the Penn State Worry Questionnaire. The findings indicate that CV activity changed according to the hypothesized pattern: A higher MAP and TPR and a lower HRV in the threat condition compared with the neutral condition were found with practically meaningful effect sizes. However, these findings were only statistically significant for TPR. Furthermore, changes in CV activity were not moderated by trait worry or resting HRV. This is the first study to explicitly address the role of subliminally presented threat words on health-relevant outcome measures and suggests that unconscious stress can influence peripheral vascular resistance. © 2017 Society for Psychophysiological Research.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

PubMed

Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

2018-04-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

PubMed Central

Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

2018-01-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

Optimization of a Plaque Neutralization Test (PNT) to identify the exposure history of Pacific Herring to viral hemorrhagic septicemia virus (VHSV)

USGS Publications Warehouse

Hart, Lucas; Mackenzie, Ashley; Purcell, Maureen; Thompson, Rachel L.; Hershberger, Paul

2017-01-01

Methods for a plaque neutralization test (PNT) were optimized for the detection and quantification of viral hemorrhagic septicemia virus (VHSV) neutralizing activity in the plasma of Pacific Herring Clupea pallasii. The PNT was complement dependent, as neutralizing activity was attenuated by heat inactivation; further, neutralizing activity was mostly restored by the addition of exogenous complement from specific-pathogen-free Pacific Herring. Optimal methods included the overnight incubation of VHSV aliquots in serial dilutions (starting at 1:16) of whole test plasma containing endogenous complement. The resulting viral titers were then enumerated using a viral plaque assay in 96-well microplates. Serum neutralizing activity was virus-specific as plasma from viral hemorrhagic septicemia (VHS) survivors demonstrated only negligible reactivity to infectious hematopoietic necrosis virus, a closely related rhabdovirus. Among Pacific Herring that survived VHSV exposure, neutralizing activity was detected in the plasma as early as 37 d postexposure and peaked at approximately 64 d postexposure. The onset of neutralizing activity was slightly delayed in fish reared at 7.4°C relative to those in warmer temperatures (9.9°C and 13.1°C); however, neutralizing activity persisted for at least 345 d postexposure in all temperature treatments. It is anticipated that this novel ability to assess VHSV neutralizing activity in Pacific Herring will enable retrospective comparisons between prior VHS infections and year-class recruitment failures. Additionally, the optimized PNT could be employed as a forecasting tool capable of identifying the potential for future VHS epizootics in wild Pacific Herring populations.

Molecular Evolution of Human PON to Design Enhanced Catalytic Efficiency for Hydrolysis of Nerve Agents

DTIC Science & Technology

2011-12-01

8   C.   Catalytic activity of evolved variants with GA ................................................................. 11   D...several variants of rePON1 with enhanced activity towards a racemic mixture of CMP-Coumarin by screening ‘neutral drift’ libraries of rePON1 (e.g. 1G3, 2G9...22. The most active variant was 3B3, which had ~250-fold higher catalytic efficiency (kcat/Km 20x106 M-1min-1) compared to the wild-type-like

The neurobiology of self-face recognition in depressed adolescents with low or high suicidality.

PubMed

Quevedo, Karina; Ng, Rowena; Scott, Hannah; Martin, Jodi; Smyda, Garry; Keener, Matt; Oppenheimer, Caroline W

2016-11-01

This study sought to test whether the neurobiology of self-processing differentiated depressed adolescents with high suicidality (HS) from those with low suicidality (LS) and healthy controls (HC; N = 119, MAGE = 14.79, SD = 1.64, Min = 11.3, Max = 17.8). Participants completed a visual self-recognition task in the scanner during which they identified their own or an unfamiliar adolescent face across 3 emotional expressions (happy, neutral or sad). A 3-group (HS, LS, HC) by 2 within-subject factors (2 Self conditions [self, other] and 3 Emotions [happy, neutral, sad]) GLM yielded (a) a main effect of Self condition with all participants showing higher activity in the right occipital, precuneus and fusiform during the self- versus other-face conditions; (b) a main effect of Group where all depressed youth showed higher dorsolateral prefrontal cortex activity than HC across all conditions, and with HS showing higher cuneus and occipital activity versus both LS and HC; and (c) a Group by Self by Emotion interaction with HS showing lower activity in both mid parietal, limbic, and prefrontal areas in the Happy self versus other-face condition relative to the LS group, who in turn had less activity compared to HC youth. Covarying for depression severity replicated all results except the third finding; In this subsequent analysis, a Group by Self interaction showed that although HC had similar midline cortical structure (MCS) activity for all faces, LS showed higher MCS activity for the self versus other faces, whereas HS showed the opposite pattern. Results suggest that the neurophysiology of emotionally charged self-referential information can distinguish depressed, suicidal youth versus nonsuicidal depressed and healthy adolescents. Neurophysiological differences and implications for the prediction of suicidality in youth are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Impact of pectin esterification on the antimicrobial activity of nisin-loaded pectin particles.

PubMed

Krivorotova, Tatjana; Staneviciene, Ramune; Luksa, Juliana; Serviene, Elena; Sereikaite, Jolanta

2017-01-01

The relationship between pectin structure and the antimicrobial activity of nisin-loaded pectin particles was examined. The antimicrobial activity of five different nisin-loaded pectin particles, i.e., nisin-loaded high methoxyl pectin, low methoxyl pectin, pectic acid, dodecyl pectin with 5.4 and 25% degree of substitution were tested in the pH range of 4.0-7.0 by agar-diffusion assay and agar plate count methods. It was found that the degree of esterification of carboxyl group of galacturonic acid in pectin molecule is important for the antimicrobial activity of nisin-loaded pectin particles. Nisin-loaded particles prepared using pectic acid or the pectin with low degree of esterification exhibit higher antimicrobial activity than nisin-loaded high methoxyl pectin particles. Pectins with free carboxyl groups or of low degree of esterification are the most suitable for particles preparation. Moreover, nisin-loaded pectin particles were active at close to neutral or neutral pH values. Therefore, they could be effectively applied for food preservation. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:245-251, 2017. © 2016 American Institute of Chemical Engineers.

HAMLET forms annular oligomers when deposited with phospholipid monolayers.

PubMed

Baumann, Anne; Gjerde, Anja Underhaug; Ying, Ming; Svanborg, Catharina; Holmsen, Holm; Glomm, Wilhelm R; Martinez, Aurora; Halskau, Oyvind

2012-04-20

Recently, the anticancer activity of human α-lactalbumin made lethal to tumor cells (HAMLET) has been linked to its increased membrane affinity in vitro, at neutral pH, and ability to cause leakage relative to the inactive native bovine α-lactalbumin (BLA) protein. In this study, atomic force microscopy resolved membrane distortions and annular oligomers (AOs) produced by HAMLET when deposited at neutral pH on mica together with a negatively charged lipid monolayer. BLA, BAMLET (HAMLET's bovine counterpart) and membrane-binding Peptide C, corresponding to BLA residues 75-100, also form AO-like structures under these conditions but at higher subphase concentrations than HAMLET. The N-terminal Peptide A, which binds to membranes at acidic but not at neutral pH, did not form AOs. This suggests a correlation between the capacity of the proteins/peptides to integrate into the membrane at neutral pH-as observed by liposome content leakage and circular dichroism experiments-and the formation of AOs, albeit at higher concentrations. Formation of AOs, which might be important to HAMLET's tumor toxic action, appears related to the increased tendency of the protein to populate intermediately folded states compared to the native protein, the formation of which is promoted by, but not uniquely dependent on, the oleic acid molecules associated with HAMLET. Copyright © 2012 Elsevier Ltd. All rights reserved.

Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

PubMed

Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

2016-02-05

Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity.

Zika virus-like particle (VLP) based vaccine

PubMed Central

Boigard, Hélène; Alimova, Alexandra; Martin, George R.; Katz, Al; Gottlieb, Paul

2017-01-01

The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development. PMID:28481898

Pitfalls in efficacy testing--how important is the validation of neutralization of chlorhexidine digluconate?

PubMed

Reichel, Mirja; Heisig, Peter; Kampf, Günter

2008-12-02

Effective neutralization of active agents is essential to obtain valid efficacy results, especially when non-volatile active agents like chlorhexidine digluconate (CHG) are tested. The aim of this study was to determine an effective and non-toxic neutralizing mixture for a propan-1-ol solution containing 2% CHG. Experiments were carried out according to ASTM E 1054-02. The neutralization capacity was tested separately with five challenge microorganisms in suspension, and with a rayon swab carrier. Either 0.5 mL of the antiseptic solution (suspension test) or a saturated swab with the antiseptic solution (carrier test) was added to tryptic soy broth containing neutralizing agents. After the samples were mixed, aliquots were spread immediately and after 3 h of storage at 2 - 8 degrees C onto tryptic soy agar containing a neutralizing mixture. The neutralizer was, however, not consistently effective in the suspension test. Immediate spread yielded a valid neutralization with Staphylococcus aureus, Staphylococcus epidermidis and Corynebacterium jeikeium but not with Micrococcus luteus (p < 0.001) and Candida albicans (p < 0.001). A 3-h storage period of the neutralized active agents in suspension resulted in significant carry-over activity of CHG in addition against Staphylococcus epidermidis (p < 0.001) and Corynebacterium jeikeium (p = 0.044). In the carrier test, the neutralizing mixture was found to be effective and non toxic to all challenge microorganisms when spread immediately. However, after 3 h storage of the neutralized active agents significant carry-over activity of CHG against Micrococcus luteus (p = 0.004; Tukey HSD) was observed. Without effective neutralization in the sampling fluid, non-volatile active ingredients will continue to reduce the number of surviving microorganisms after antiseptic treatment even if the sampling fluid is kept cold straight after testing. This can result in false-positive antiseptic efficacy data. Attention should be paid during the neutralization validation process to the amount of antiseptic solution, the storage time and to the choice of appropriate and sensitive microorganisms.

Immunodominance and Functional Activities of Antibody Responses to Inactivated West Nile Virus and Recombinant Subunit Vaccines in Mice▿

PubMed Central

Zlatkovic, Juergen; Stiasny, Karin; Heinz, Franz X.

2011-01-01

Factors controlling the dominance of antibody responses to specific sites in viruses and/or protein antigens are ill defined but can be of great importance for the induction of potent immune responses to vaccines. West Nile virus and other related important human-pathogenic flaviviruses display the major target of neutralizing antibodies, the E protein, in an icosahedral shell at the virion surface. Potent neutralizing antibodies were shown to react with the upper surface of domain III (DIII) of this protein. Using the West Nile virus system, we conducted a study on the immunodominance and functional quality of E-specific antibody responses after immunization of mice with soluble protein E (sE) and isolated DIII in comparison to those after immunization with inactivated whole virions. With both virion and sE, the neutralizing response was dominated by DIII-specific antibodies, but the functionality of these antibodies was almost four times higher after virion immunization. Antibodies induced by the isolated DIII had an at least 15-fold lower specific neutralizing activity than those induced by the virion, and only 50% of these antibodies were able to bind to virus particles. Our results suggest that immunization with the tightly packed E in virions focuses the DIII antibody response to the externally exposed sites of this domain which are the primary targets for virus neutralization, different from sE and isolated DIII, which also display protein surfaces that are cryptic in the virion. Despite its low potency for priming, DIII was an excellent boosting antigen, suggesting novel vaccination strategies that strengthen and focus the antibody response to critical neutralizing sites in DIII. PMID:21147919

Stress examination of flexor tendon pulley rupture in the crimp grip position: a 1.5-Tesla MRI cadaver study.

PubMed

Bayer, Thomas; Fries, Simon; Schweizer, Andreas; Schöffl, Isabelle; Janka, Rolf; Bongartz, Georg

2015-01-01

The objectives of this study were the evaluation of flexor tendon pulley rupture of the fingers in the crimp grip position using magnetic resonance imaging (MRI) and the comparison of the results with MRI in the neutral position in a cadaver study. MRI in the crimp grip position and in the neutral position was performed in 21 cadaver fingers with artificially created flexor tendon pulley tears (combined pulley rupture, n = 14; single pulley rupture, n = 7). Measurement of the distance between the tendon and bone was performed. Images were evaluated by two readers, first independently and in cases of discrepancy in consensus. Sensitivity and specificity for detecting combined pulley ruptures were calculated. Tendon bone distances were significantly higher in the crimp grip position than in the neutral position. Sensitivity and specificity for detecting combined pulley rupture were 92.86 % and 100 % respectively in the crimp grip position and 78.57 % and 85.71 % respectively in the neutral position. Kappa values for interobserver reliability were 0.87 in the crimp grip position and 0.59 in the neutral position. MRI examination in the crimp grip position results in higher tendon bone distances by subjecting the pulleys to a higher strain, which facilitates image evaluation with higher interobserver reliability, higher sensitivity, and higher specificity for combined pulley rupture compared with examination in the neutral position.

Emotional and neutral scenes in competition: orienting, efficiency, and identification.

PubMed

Calvo, Manuel G; Nummenmaa, Lauri; Hyönä, Jukka

2007-12-01

To investigate preferential processing of emotional scenes competing for limited attentional resources with neutral scenes, prime pictures were presented briefly (450 ms), peripherally (5.2 degrees away from fixation), and simultaneously (one emotional and one neutral scene) versus singly. Primes were followed by a mask and a probe for recognition. Hit rate was higher for emotional than for neutral scenes in the dual- but not in the single-prime condition, and A' sensitivity decreased for neutral but not for emotional scenes in the dual-prime condition. This preferential processing involved both selective orienting and efficient encoding, as revealed, respectively, by a higher probability of first fixation on--and shorter saccade latencies to--emotional scenes and by shorter fixation time needed to accurately identify emotional scenes, in comparison with neutral scenes.

Carbon-neutral energy cycles using alcohols.

PubMed

Fukushima, Takashi; Kitano, Sho; Hata, Shinichi; Yamauchi, Miho

2018-01-01

We demonstrated carbon-neutral (CN) energy circulation using glycolic acid ( GC )/oxalic acid ( OX ) redox couple. Here, we report fundamental studies on both catalyst search for power generation process, i.e. GC oxidation, and elemental steps for fuel generation process, i.e. OX reduction, in CN cycle. The catalytic activity test on various transition metals revealed that Rh, Pd, Ir, and Pt have preferable features as a catalyst for electrochemical oxidation of GC . A carbon-supported Pt catalyst in alkaline conditions exhibited higher activity, durability, and product selectivity for electrooxidation of GC rather than those in acidic media. The kinetic study on OX reduction clearly indicated that OX reduction undergoes successive two-electron reductions to form GC . Furthermore, application of TiO 2 catalysts with large specific area for electrochemical reduction of OX facilitates the selective formation of GC .

Carbon-neutral energy cycles using alcohols

PubMed Central

Fukushima, Takashi; Kitano, Sho; Hata, Shinichi; Yamauchi, Miho

2018-01-01

Abstract We demonstrated carbon-neutral (CN) energy circulation using glycolic acid (GC)/oxalic acid (OX) redox couple. Here, we report fundamental studies on both catalyst search for power generation process, i.e. GC oxidation, and elemental steps for fuel generation process, i.e. OX reduction, in CN cycle. The catalytic activity test on various transition metals revealed that Rh, Pd, Ir, and Pt have preferable features as a catalyst for electrochemical oxidation of GC. A carbon-supported Pt catalyst in alkaline conditions exhibited higher activity, durability, and product selectivity for electrooxidation of GC rather than those in acidic media. The kinetic study on OX reduction clearly indicated that OX reduction undergoes successive two-electron reductions to form GC. Furthermore, application of TiO2 catalysts with large specific area for electrochemical reduction of OX facilitates the selective formation of GC. PMID:29511392

Neural Mechanisms of Selective Attention in Children with Amblyopia.

PubMed

Zhou, Aibao; Jiang, Yanfei; Chen, Jianming; Wei, Jianlan; Dang, Baobao; Li, Shifeng; Xu, Qiongying

2015-01-01

Previous studies have indicated that amblyopia might affect children's attention. We recruited amblyopic children and normal children aged 9-11 years as study subjects and compared selective attention between the two groups of children. Chinese characters denoting colors were used in the Stroop task, and the event-related potential (ERP) was analyzed. The results show that the accuracy of both groups in the congruent condition was higher than the incongruent condition, and the reaction time (RT) of amblyopic children was longer. The latency of the occipital P1 in the incongruent condition was shorter than the neutral condition for both groups; the peak of the occipital P1 elicited by the incongruent stimuli in amblyopic children was higher. In both groups, the N1 peak was higher in the occipital region than frontal and central regions. The N1 latency of normal children was shorter in the congruent and neutral conditions and longer in the incongruent condition; the N1 peak of normal children was higher. The N270 latencies of normal children in the congruent and neutral conditions were shorter; the N270 peak was higher in parietal and occipital regions than frontal and central regions for both groups. The N450 latency of normal children was shorter; in both groups, the N450 average amplitude was significantly higher in the parietal region than central and frontal regions. The accuracy was the same for both groups, but the response of amblyopic children was significantly slower. The two groups showed differences in both stages of the Stroop task. Normal children showed advantages in processing speed on both stimulus and response conflict stages.Brain regions activated during the Stroop task were consistent between groups, in line with their age characteristics.

Isolation of Alkaline and Neutral Proteases from Aspergillus flavus var. columnaris, a Soy Sauce Koji Mold

PubMed Central

Impoolsup, Attawut; Bhumiratana, Amaret; Flegel, Timothy W.

1981-01-01

Two different extracellular proteases, protease I (P-I), an alkaline protease, and protease II (P-II) a neutral protease, from Aspergillus flavus var. columnaris were partially purified by using (NH4)2SO4 precipitation, diethylaminoethyl-Sephadex A-50 chromatography, carboxymethylcellulose CM-52 chromatography, and Sephadex G-100 gel filtration. The degree of purity was followed using polyacrylamide gel electrophoresis. The activity of P-I was completely inhibited by 0.1 mM phenylmethylsulfonyl fluoride, and that of P-II was completely inhibited by 1 mM ethylenediaminetetraacetate. By using these inhibitors with extracts of wheat bran koji, the proportions of total activity that could be assigned to P-I and P-II were 80 and 20%, respectively. This compared favorably with activities estimated by using polyacrylamide gel electrophoresis slices (82 and 18%, respectively). Extracts from factory-run soybean koji gave comparable results. Both enzymes demonstrated maximum activity at 50 to 55°C and only small changes in activity between pH 6 and 11. For P-I, activity was somewhat higher from pH 8.0 to 11.0, whereas for P-II it was somewhat higher from pH 6 to 9. In the presence of 18% NaCl, the activities of both P-I and P-II dropped by approximately 90 and 85%, respectively. P-I was inferred to possess aminopeptidase activity since it could hydrolyze l-leucyl-p-nitroanilide hydrochloride. P-II was devoid of such activity. The ramifications of the results for factory-produced soy sauce koji are discussed. Images PMID:16345858

Negative words enhance recognition in nonclinical high dissociators: An fMRI study.

PubMed

de Ruiter, Michiel B; Veltman, Dick J; Phaf, R Hans; van Dyck, Richard

2007-08-01

Memory encoding and retrieval were studied in a nonclinical sample of participants that differed in the amount of reported dissociative experiences (trait dissociation). Behavioral as well as functional imaging (fMRI) indices were used as convergent measures of memory functioning. In a deep vs. shallow encoding paradigm, the influence of dissociative style on elaborative and avoidant encoding was studied, respectively. Furthermore, affectively neutral and negative words were presented, to test whether the effects of dissociative tendencies on memory functioning depended on the affective valence of the stimulus material. Results showed that (a) deep encoding of negative vs. neutral stimuli was associated with higher levels of semantic elaboration in high than in low dissociators, as indicated by increased levels of activity in hippocampus and prefrontal cortex during encoding and higher memory performance during recognition, (b) high dissociators were generally characterized by higher levels of conscious recollection as indicated by increased activity of the hippocampus and posterior parietal areas during recognition, (c) nonclinical high dissociators were not characterized by an avoidant encoding style. These results support the notion that trait dissociation in healthy individuals is associated with high levels of elaborative encoding, resulting in high levels of conscious recollection. These abilities, in addition, seem to depend on the salience of the presented stimulus material.

Influence of natural organic matter on equilibrium adsorption of neutral and charged pharmaceuticals onto activated carbon.

PubMed

de Ridder, D J; Verliefde, A R D; Heijman, S G J; Verberk, J Q J C; Rietveld, L C; van der Aa, L T J; Amy, G L; van Dijk, J C

2011-01-01

Natural organic matter (NOM) can influence pharmaceutical adsorption onto granular activated carbon (GAC) by direct adsorption competition and pore blocking. However, in the literature there is limited information on which of these mechanisms is more important and how this is related to NOM and pharmaceutical properties. Adsorption batch experiments were carried out in ultrapure, waste- and surface water and fresh and NOM preloaded GAC was used. Twenty-one pharmaceuticals were selected with varying hydrophobicity and with neutral, negative or positive charge. The influence of NOM competition and pore blocking could not be separated. However, while reduction in surface area was similar for both preloaded GACs, up to 50% lower pharmaceutical removal was observed on wastewater preloaded GAC. This was attributed to higher hydrophobicity of wastewater NOM, indicating that NOM competition may influence pharmaceutical removal more than pore blocking. Preloaded GAC was negatively charged, which influenced removal of charged pharmaceuticals significantly. At a GAC dose of 6.7 mg/L, negatively charged pharmaceuticals were removed for 0-58%, while removal of positively charged pharmaceuticals was between 32-98%. Charge effects were more pronounced in ultrapure water, as it contained no ions to shield the surface charge. Solutes with higher log D could compete better with NOM, resulting in higher removal.

Ion energy balance in enhanced-confinement reversed-field pinch plasmas

NASA Astrophysics Data System (ADS)

Xing, Z. A.; Nornberg, M. D.; Boguski, J.; Craig, D.; den Hartog, D. J.; McCollam, K.

2017-10-01

Testing the applicability of collisional ion transport theory using tearing suppressed RFP plasma in MST achieved through Pulsed Poloidal Current Drive (PPCD), we find that the ion temperature dynamics in the core to be well-predicted by classical and collisional terms. Prior work demonstrated that impurity ion particle transport in PPCD plasmas is classical. Neoclassical effects on ions in the RFP are small and the stochastic transport is greatly suppressed during PPCD. Recent neutral modelling with DEGAS2 suggests higher core neutral temperatures than expected due to the preferential penetration of higher temperature neutrals generated by charge exchange. Further, investigations through equilibrium reconstruction point to the existence of an inward pinch flow associated with ExB drift. The heat balance model pulls together a wide range of diagnostic data to forward model Ti evolution in PPCD, which is then compared to charge exchange spectroscopy measurements of Ti. Ion power balance is mostly driven by classical effects including compressional heating, electron collisional heating, and charge exchange transport. This understanding provides a good baseline for investigations of anomalous heating in plasmas with tearing mode activity. This work is supported by US DOE.

Is a neutral expression also a neutral stimulus? A study with functional magnetic resonance.

PubMed

Carvajal, Fernando; Rubio, Sandra; Serrano, Juan M; Ríos-Lago, Marcos; Alvarez-Linera, Juan; Pacheco, Lara; Martín, Pilar

2013-08-01

Although neutral faces do not initially convey an explicit emotional message, it has been found that individuals tend to assign them an affective content. Moreover, previous research has shown that affective judgments are mediated by the task they have to perform. Using functional magnetic resonance imaging in 21 healthy participants, we focus this study on the cerebral activity patterns triggered by neutral and emotional faces in two different tasks (social or gender judgments). Results obtained, using conjunction analyses, indicated that viewing both emotional and neutral faces evokes activity in several similar brain areas indicating a common neural substrate. Moreover, neutral faces specifically elicit activation of cerebellum, frontal and temporal areas, while emotional faces involve the cuneus, anterior cingulated gyrus, medial orbitofrontal cortex, posterior superior temporal gyrus, precentral/postcentral gyrus and insula. The task selected was also found to influence brain activity, in that the social task recruited frontal areas while the gender task involved the posterior cingulated, inferior parietal lobule and middle temporal gyrus to a greater extent. Specifically, in the social task viewing neutral faces was associated with longer reaction times and increased activity of left dorsolateral frontal cortex compared with viewing facial expressions of emotions. In contrast, in the same task emotional expressions distinctively activated the left amygdale. The results are discussed taking into consideration the fact that, like other facial expressions, neutral expressions are usually assigned some emotional significance. However, neutral faces evoke a greater activation of circuits probably involved in more elaborate cognitive processing.

Antigenic properties of the envelope of influenza virus rendered soluble by surfactant-solvent systems

PubMed Central

Larin, N. M.; Gallimore, P. H.

1971-01-01

Dissociating chemical treatments employing surfactant-solvent systems were applied to purified influenza A and B viruses to obtain viral preparations possessing a significantly higher or lower haemagglutinating activity than the intact virus. All preparations, whether with high or low haemagglutinating activity, with the exception of envelope protein solubilized by Triton X-100, were significantly lacking in the ability to excite the formation of haemagglutination-inhibiting and virus-neutralizing antibodies in inoculated ferrets. In contrast to other treatments, Triton X-100 treatment of virus significantly enhanced the antigenicity of viral protein as judged by virus neutralization and haemagglutination inhibition tests. Yet the haemagglutinating activity of the envelope protein solubilized with Triton X-100 was about 1% that of the intact virus. Results suggest that the correlation assumed to exist between the haemagglutinating activity of influenza virus and its ability to excite the formation of humoral antibodies is coincidental. Another important point is that the specific antigenicity of viral protein may be lost or enhanced owing to effects, other than solubilization, by surface-active agents. PMID:5291750

HIV-Specific Functional Antibody Responses in Breast Milk Mirror Those in Plasma and Are Primarily Mediated by IgG Antibodies ▿

PubMed Central

Fouda, Genevieve G.; Yates, Nicole L.; Pollara, Justin; Shen, Xiaoying; Overman, Glenn R.; Mahlokozera, Tatenda; Wilks, Andrew B.; Kang, Helen H.; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Kalilani, Linda; Meshnick, Steve R.; Hahn, Beatrice H.; Shaw, George M.; Lovingood, Rachel V.; Denny, Thomas N.; Haynes, Barton; Letvin, Norman L.; Ferrari, Guido; Montefiori, David C.; Tomaras, Georgia D.; Permar, Sallie R.

2011-01-01

Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies are present in the milk of HIV-infected mothers, but little is known about their virus-specific functions. In this study, HIV Env-specific antibody binding, autologous and heterologous virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001) in milk were directly correlated with that in the systemic compartment but were 2 log units lower in magnitude. Autologous neutralization was rarely detected in milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r = 0.17 and P = 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies against a tier 1 virus (r = 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG milk fractions had detectable neutralization. These results suggest that plasma-derived IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity in breast milk. PMID:21734046

What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

PubMed

Oliveira, Leticia; Ladouceur, Cecile D; Phillips, Mary L; Brammer, Michael; Mourao-Miranda, Janaina

2013-01-01

A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. TWO INDEPENDENT DEPRESSED SAMPLES: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in brain activation might underlie the behavioural misinterpretation of the neutral faces content by the depressed patients.

Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization.

PubMed

Ji, Xin; Olinger, Gene G; Aris, Sheena; Chen, Ying; Gewurz, Henry; Spear, Gregory T

2005-09-01

Mannose-binding lectin (MBL), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. In this study, the ability of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain) or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized MBL compared with virus particles pseudotyped with vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As observed in previous studies, Ebola-pseudotyped virus bound to cells expressing the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN-mediated binding to cells, suggesting that the two lectins bind at the same or overlapping sites on the Ebola glycoprotein. Neutralization experiments showed that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was neutralized by complement, while the Marburg (Ravn strain) glycoprotein-pseudotyped virus was less sensitive to neutralization. Neutralization was partially mediated through the lectin complement pathway, since a complement source deficient in MBL was significantly less effective at neutralizing viruses pseudotyped with filovirus glycoproteins and addition of purified MBL to the MBL-deficient complement increased neutralization. These experiments demonstrated that MBL binds to filovirus envelope glycoproteins resulting in important biological effects and suggest that MBL can interact with filoviruses during infection in humans.

Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library.

PubMed

Wang, Han; Yu, Rui; Fang, Ting; Yu, Ting; Chi, Xiangyang; Zhang, Xiaopeng; Liu, Shuling; Fu, Ling; Yu, Changming; Chen, Wei

2016-09-11

Tetanus neurotoxin (TeNT) produced by Clostridium tetani is one of the most poisonous protein substances. Neutralizing antibodies against TeNT can effectively prevent and cure toxicosis. Using purified Hc fragments of TeNT (TeNT-Hc) as an antigen, three specific neutralizing antibody clones recognizing different epitopes were selected from a human immune scFv antibody phage display library. The three antibodies (2-7G, 2-2D, and S-4-7H) can effectively inhibit the binding between TeNT-Hc and differentiated PC-12 cells in vitro. Moreover, 2-7G inhibited TeNT-Hc binding to the receptor via carbohydrate-binding sites of the W pocket while 2-2D and S-4-7H inhibited binding of the R pocket. Although no single mAb completely protected mice from the toxin, they could both prolong survival when challenged with 20 LD50s (50% of the lethal dose) of TeNT. When used together, the mAbs completely neutralized 1000 LD50s/mg Ab, indicating their high neutralizing potency in vivo. Antibodies recognizing different carbohydrate-binding pockets could have higher synergistic toxin neutralization activities than those that recognize the same pockets. These results could lead to further production of neutralizing antibody drugs against TeNT and indicate that using TeNT-Hc as an antigen for screening human antibodies for TeNT intoxication therapy from human immune antibody library was convenient and effective.

Chemical composition of rosehips from different Rosa species: an alternative source of antioxidants for the food industry.

PubMed

Jiménez, Sandra; Jiménez-Moreno, Nerea; Luquin, Asunción; Laguna, Mariano; Rodríguez-Yoldi, María Jesús; Ancín-Azpilicueta, Carmen

2017-07-01

It is important to explore new sources of natural additives because the demand for these compounds by consumers is increasing. These products also provide health benefits and help in food preservation. An unexplored source of nutrients and antioxidant compounds is rosehip, the fleshy fruit of roses. This work compares the antioxidant compound (vitamin C, neutral phenols and acidic phenols) content of four Rosa species rosehips: R. pouzinii, R. corymbifera, R. glauca and R. canina from different geographical zones. Results show quantitative variability in ascorbic acids and neutral phenols content, and quantitative and qualitative differences in acidic phenol content, depending on species. Vitamin C concentration was highly variable depending on species, R. canina being the one with the highest concentration and R. pouzinii the one with the lowest content. Variability was found in total neutral polyphenols concentration and a correlation between freshness of the rosehips and concentration of neutral polyphenols was also found. Significant differences were found in the acidic phenols content among the studied species. Generally antioxidant activity was higher in the vitamin C fraction.

Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort

PubMed Central

Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin; Murrell, Ben; Price, Matt A.; Wickramasinghe, Lalinda; Ramos, Alejandra; Bian, Charoan B.; Simek, Melissa; Allen, Susan; Karita, Etienne; Kilembe, William; Lakhi, Shabir; Inambao, Mubiana; Kamali, Anatoli; Sanders, Eduard J.; Anzala, Omu; Edward, Vinodh; Bekker, Linda-Gail; Tang, Jianming; Gilmour, Jill; Kosakovsky-Pond, Sergei L.; Phung, Pham; Wrin, Terri; Crotty, Shane; Godzik, Adam; Poignard, Pascal

2016-01-01

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design. PMID:26766578

Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

PubMed

Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin; Murrell, Ben; Price, Matt A; Wickramasinghe, Lalinda; Ramos, Alejandra; Bian, Charoan B; Simek, Melissa; Allen, Susan; Karita, Etienne; Kilembe, William; Lakhi, Shabir; Inambao, Mubiana; Kamali, Anatoli; Sanders, Eduard J; Anzala, Omu; Edward, Vinodh; Bekker, Linda-Gail; Tang, Jianming; Gilmour, Jill; Kosakovsky-Pond, Sergei L; Phung, Pham; Wrin, Terri; Crotty, Shane; Godzik, Adam; Poignard, Pascal

2016-01-01

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

Processing emotional words in two languages with one brain: ERP and fMRI evidence from Chinese-English bilinguals.

PubMed

Chen, Peiyao; Lin, Jie; Chen, Bingle; Lu, Chunming; Guo, Taomei

2015-10-01

Emotional words in a bilingual's second language (L2) seem to have less emotional impact compared to emotional words in the first language (L1). The present study examined the neural mechanisms of emotional word processing in Chinese-English bilinguals' two languages by using both event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI). Behavioral results show a robust positive word processing advantage in L1 such that responses to positive words were faster and more accurate compared to responses to neutral words and negative words. In L2, emotional words only received higher accuracies than neutral words. In ERPs, positive words elicited a larger early posterior negativity and a smaller late positive component than neutral words in L1, while a trend of reduced N400 component was found for positive words compared to neutral words in L2. In fMRI, reduced activation was found for L1 emotional words in both the left middle occipital gyrus and the left cerebellum whereas increased activation in the left cerebellum was found for L2 emotional words. Altogether, these results suggest that emotional word processing advantage in L1 relies on rapid and automatic attention capture while facilitated semantic retrieval might help processing emotional words in L2. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aqueous Cr(VI) reduction by electrodeposited zero-valent iron at neutral pH: acceleration by organic matters.

PubMed

Liu, Junxi; Wang, Chuan; Shi, Jianying; Liu, Hong; Tong, Yexiang

2009-04-15

This work investigated the effect of co-existing organic matters on aqueous Cr(VI) reduction by electrodeposited zero-valent iron (ED Fe(0)) at neutral pH. The ED Fe(0) prepared in a solution containing mixture of saccharin, L-ascorbic acid and sodium dodecyl sulfate showed higher activity in reducing the aqueous Cr(VI) at neutral pH than that prepared without any organic presence. XRD and SEM indicated that the structure of ED Fe(0) was significantly improved to nano-scale by the presence of organic mixture in the preparation solution. Further, the ED Fe(0) activity in the Cr(VI) reduction at neutral pH was increased by the co-existence of citric acid or oxalic acid in the chromate solution. Electrochemical impedance spectroscopy (EIS) demonstrated that the corrosive current increased with the concentration of organic matter in the reaction solution. With the co-existing organic matters in the preparation solution, the ED Fe(0) corroded more rapidly due to its nano-size, thus the Cr(VI) reduction by the ferrous iron was accelerated. With the co-existing organic matters in the reaction solution, the Cr(VI) reduction was accelerated by a Fe(II) complex as the main electron donor, and a prevention of the passivation due to the Fe(III) and Cr(III) complexes also accelerated the Cr(VI) reduction.

Human sweet taste receptor mediates acid-induced sweetness of miraculin

PubMed Central

Koizumi, Ayako; Tsuchiya, Asami; Nakajima, Ken-ichiro; Ito, Keisuke; Terada, Tohru; Shimizu-Ibuka, Akiko; Briand, Loïc; Asakura, Tomiko; Misaka, Takumi; Abe, Keiko

2011-01-01

Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity. PMID:21949380

Electromyographic analysis of gluteus maximus and hamstring activity during the supine resisted hip extension exercise versus supine unilateral bridge to neutral.

PubMed

Youdas, James W; Hartman, James P; Murphy, Brooke A; Rundle, Ashley M; Ugorowski, Jenna M; Hollman, John H

2017-02-01

Hip extension strengthening exercises which maximize gluteus maximus contributions and minimize hamstring influences may be beneficial for persons with hip pain. This study's aim was to compare muscle activation of the gluteus maximus and hamstrings from healthy subjects during a supine resisted hip extension exercise versus supine unilateral bridge to neutral. Surface electromyographic (EMG) signals were obtained from the right gluteus maximus and hamstrings in 13 healthy male and 13 healthy female subjects. Maximum voluntary isometric contractions (MVICs) were collected to normalize data and permit meaningful comparisons across muscles. Peak median activation of the gluteus maximus was 33.8% MVIC for the bridge and 34.7% MVIC for the hip extension exercise, whereas peak median recruitment for hamstrings was 28.4% MVIC for the bridge and 51% MVIC for the hip extension exercise. The gluteus maximus to hamstrings ratio was compared between the two exercises using the Wilcoxon signed-ranks test (α = 0.05). The ratio (p = 0.014) was greater in the supine unilateral bridge (median = 111.3%) than supine hip extension exercise (median = 59.2%), suggesting a reduction of hamstring recruitment in the unilateral bridge to neutral compared to the supine resisted hip extension exercise. The supine hip extension exercise demonstrated higher EMG activity of hamstrings in comparison with supine unilateral bridge and, therefore, may be less appropriate in subjects who need to increase gluteus maximus activation.

Brain activation while forming memories of fearful and neutral faces in women and men.

PubMed

Fischer, Håkan; Sandblom, Johan; Nyberg, Lars; Herlitz, Agneta; Bäckman, Lars

2007-11-01

Event-related functional MRI (fMRI) was used to assess brain activity during encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent memory analysis, the authors separated successful from unsuccessful encoding of both types of faces, based on whether they were remembered or forgotten in a later recognition memory test. Overall, women and men recruited overlapping neural circuitries. Both sexes activated right-sided medial-temporal regions during successful encoding of fearful faces. Successful encoding of neutral faces was associated with left-sided lateral prefrontal and right-sided superior frontal activation in both sexes. In women, relatively greater encoding related activity for neutral faces was seen in the superior parietal and parahippocampal cortices. By contrast, men activated the left and right superior/middle frontal cortex more than women during successful encoding of the same neutral faces. These findings suggest that women and men use similar neural networks to encode facial information, with only subtle sex differences observed for neutral faces.

Pitfalls in efficacy testing – how important is the validation of neutralization of chlorhexidine digluconate?

PubMed Central

Reichel, Mirja; Heisig, Peter; Kampf, Günter

2008-01-01

Background Effective neutralization of active agents is essential to obtain valid efficacy results, especially when non-volatile active agents like chlorhexidine digluconate (CHG) are tested. The aim of this study was to determine an effective and non-toxic neutralizing mixture for a propan-1-ol solution containing 2% CHG. Methods Experiments were carried out according to ASTM E 1054-02. The neutralization capacity was tested separately with five challenge microorganisms in suspension, and with a rayon swab carrier. Either 0.5 mL of the antiseptic solution (suspension test) or a saturated swab with the antiseptic solution (carrier test) was added to tryptic soy broth containing neutralizing agents. After the samples were mixed, aliquots were spread immediately and after 3 h of storage at 2 – 8°C onto tryptic soy agar containing a neutralizing mixture. Results The neutralizer was, however, not consistently effective in the suspension test. Immediate spread yielded a valid neutralization with Staphylococcus aureus, Staphylococcus epidermidis and Corynebacterium jeikeium but not with Micrococcus luteus (p < 0.001) and Candida albicans (p < 0.001). A 3-h storage period of the neutralized active agents in suspension resulted in significant carry-over activity of CHG in addition against Staphylococcus epidermidis (p < 0.001) and Corynebacterium jeikeium (p = 0.044). In the carrier test, the neutralizing mixture was found to be effective and non toxic to all challenge microorganisms when spread immediately. However, after 3 h storage of the neutralized active agents significant carry-over activity of CHG against Micrococcus luteus (p = 0.004; Tukey HSD) was observed. Conclusion Without effective neutralization in the sampling fluid, non-volatile active ingredients will continue to reduce the number of surviving microorganisms after antiseptic treatment even if the sampling fluid is kept cold straight after testing. This can result in false-positive antiseptic efficacy data. Attention should be paid during the neutralization validation process to the amount of antiseptic solution, the storage time and to the choice of appropriate and sensitive microorganisms. PMID:19046465

The influence of personality on neural mechanisms of observational fear and reward learning

PubMed Central

Hooker, Christine I.; Verosky, Sara C.; Miyakawa, Asako; Knight, Robert T.; D’Esposito, Mark

2012-01-01

Fear and reward learning can occur through direct experience or observation. Both channels can enhance survival or create maladaptive behavior. We used fMRI to isolate neural mechanisms of observational fear and reward learning and investigate whether neural response varied according to individual differences in neuroticism and extraversion. Participants learned object-emotion associations by observing a woman respond with fearful (or neutral) and happy (or neutral) facial expressions to novel objects. The amygdala-hippocampal complex was active when learning the object-fear association, and the hippocampus was active when learning the object-happy association. After learning, objects were presented alone; amygdala activity was greater for the fear (vs. neutral) and happy (vs. neutral) associated object. Importantly, greater amygdala-hippocampal activity during fear (vs. neutral) learning predicted better recognition of learned objects on a subsequent memory test. Furthermore, personality modulated neural mechanisms of learning. Neuroticism positively correlated with neural activity in the amygdala and hippocampus during fear (vs. neutral) learning. Low extraversion/high introversion was related to faster behavioral predictions of the fearful and neutral expressions during fear learning. In addition, low extraversion/high introversion was related to greater amygdala activity during happy (vs. neutral) learning, happy (vs. neutral) object recognition, and faster reaction times for predicting happy and neutral expressions during reward learning. These findings suggest that neuroticism is associated with an increased sensitivity in the neural mechanism for fear learning which leads to enhanced encoding of fear associations, and that low extraversion/high introversion is related to enhanced conditionability for both fear and reward learning. PMID:18573512

Ex vivo effects of an Oenothera paradoxa extract on the reactive oxygen species generation and neutral endopeptidase activity in neutrophils from patients after acute myocardial infarction.

PubMed

Kiss, Anna K; Kapłon-Cieślicka, Agnieszka; Filipiak, Krzysztof J; Opolski, Grzegorz; Naruszewicz, Marek

2012-04-01

Oxidative stress induced by reactive oxygen species (ROS) is considered to play an important part in the aetiology of coronary heart disease. Apart from ROS, neutrophils are a source of neutral endopeptidase (NEP) that inactivates protective natriuretic peptides. The aim of the present study was to evaluate the in vitro ROS generation and inhibition of NEP activity in neutrophils obtained from healthy volunteers and from patients after acute myocardial infarction (AMI) by an aqueous extract of Oenothera paradoxa. Neutrophils isolated from AMI patients showed two-fold higher ROS generation compared with cells from healthy donors, especially in the lucigenin-enhanced luminescence model, which suggests intensive O₂⁻ generation. The addition of O. paradoxa extract at concentrations of 0.2, 2 and 20 µg/mL resulted in a significant reduction in ROS generation. The extracellular NEP activity was higher in patients after AMI compared with healthy individuals (15.0 ± 0.9 versus 10.3 ± 0.5 nmol AMC/10(6) cells/60 min; p = 0.001). The addition of O. paradoxa extract at concentrations of 20, 50 and 100 µg/mL resulted in a significant reduction in NEP activity in both groups. O. paradoxa extract appears to be an interesting candidate for supplementation in the prevention of cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.

Simulation of the effects of different pilot helmets on neck loading during air combat.

PubMed

Mathys, R; Ferguson, S J

2012-09-21

New generation pilot helmets with mounted devices enhance the capabilities of pilots substantially. However, the additional equipment increases the helmet weight and shifts its center of mass forward. Two helmets with different mass properties were modeled to simulate their effects on the pilot's neck. A musculoskeletal computer model was used, with the methods of inverse dynamics and static optimization, to compute the muscle activations and joint reaction forces for a given range of quasi-static postures at various accelerations experienced during air combat. Head postures which induce much higher loads on the cervical spine than encountered in a neutral position could be identified. The increased weight and the forward shift of the center of mass of a new generation helmet lead to higher muscle activations and higher joint reaction loads over a wide range of head and neck movements. The muscle activations required to balance the head and neck in extreme postures increased the compressive force at the T1-C7 level substantially, while in a neutral posture the muscle activations remained low. The lateral neck muscles can reach activations of 100% and cause compressive joint forces up to 1100N during extensive rotations and extensions at high 'vertical' accelerations (Gz). The calculated values have to be interpreted with care as the model has not been validated. Nevertheless, this systematic analysis could separate the effects of head posture, acceleration and helmet mass on neck loading. More reliable data about mass properties and muscle morphometry with a more detailed motion analysis would help to refine the existing model. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment.

PubMed

van Harmelen, Anne-Laura; van Tol, Marie-José; Dalgleish, Tim; van der Wee, Nic J A; Veltman, Dick J; Aleman, André; Spinhoven, Philip; Penninx, Brenda W J H; Elzinga, Bernet M

2014-12-01

Childhood emotional maltreatment (CEM) has adverse effects on medial prefrontal cortex (mPFC) morphology, a structure that is crucial for cognitive functioning and (emotional) memory and which modulates the limbic system. In addition, CEM has been linked to amygdala hyperactivity during emotional face processing. However, no study has yet investigated the functional neural correlates of neutral and emotional memory in adults reporting CEM. Using functional magnetic resonance imaging, we investigated CEM-related differential activations in mPFC during the encoding and recognition of positive, negative and neutral words. The sample (N = 194) consisted of patients with depression and/or anxiety disorders and healthy controls (HC) reporting CEM (n = 96) and patients and HC reporting no abuse (n = 98). We found a consistent pattern of mPFC hypoactivation during encoding and recognition of positive, negative and neutral words in individuals reporting CEM. These results were not explained by psychopathology or severity of depression or anxiety symptoms, or by gender, level of neuroticism, parental psychopathology, negative life events, antidepressant use or decreased mPFC volume in the CEM group. These findings indicate mPFC hypoactivity in individuals reporting CEM during emotional and neutral memory encoding and recognition. Our findings suggest that CEM may increase individuals' risk to the development of psychopathology on differential levels of processing in the brain; blunted mPFC activation during higher order processing and enhanced amygdala activation during automatic/lower order emotion processing. These findings are vital in understanding the long-term consequences of CEM. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Well-being and Anticipation for Future Positive Events: Evidences from an fMRI Study.

PubMed

Luo, Yangmei; Chen, Xuhai; Qi, Senqing; You, Xuqun; Huang, Xiting

2017-01-01

Anticipation for future confers great benefits to human well-being and mental health. However, previous work focus on how people's well-being correlate with brain activities during perception of emotional stimuli, rather than anticipation for the future events. Here, the current study investigated how well-being relates to neural circuitry underlying the anticipating process of future desired events. Using event-related functional magnetic resonance imaging, 40 participants were scanned while they were performing an emotion anticipation task, in which they were instructed to anticipate the positive or neutral events. The results showed that bilateral medial prefrontal cortex (MPFC) were activated during anticipation for positive events relative to neutral events, and the enhanced brain activation in MPFC was associated with higher level of well-being. The findings suggest a neural mechanism by which the anticipation process to future desired events correlates to human well-being, which provide a future-oriented view on the neural sources of well-being.

Well-being and Anticipation for Future Positive Events: Evidences from an fMRI Study

PubMed Central

Luo, Yangmei; Chen, Xuhai; Qi, Senqing; You, Xuqun; Huang, Xiting

2018-01-01

Anticipation for future confers great benefits to human well-being and mental health. However, previous work focus on how people’s well-being correlate with brain activities during perception of emotional stimuli, rather than anticipation for the future events. Here, the current study investigated how well-being relates to neural circuitry underlying the anticipating process of future desired events. Using event-related functional magnetic resonance imaging, 40 participants were scanned while they were performing an emotion anticipation task, in which they were instructed to anticipate the positive or neutral events. The results showed that bilateral medial prefrontal cortex (MPFC) were activated during anticipation for positive events relative to neutral events, and the enhanced brain activation in MPFC was associated with higher level of well-being. The findings suggest a neural mechanism by which the anticipation process to future desired events correlates to human well-being, which provide a future-oriented view on the neural sources of well-being. PMID:29375415

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

Petty, C. C., E-mail: petty@fusion.gat.com; Van Zeeland, M. A.; Pace, D. C.

“Steady-state” hybrid plasmas in DIII-D with zero surface loop voltage have been maintained for up to two current relaxation times using 3.4 MW of central electron cyclotron current drive (ECCD). In addition to driving ≈0.2 MA of plasma current, central ECCD leads to significant changes in Alfvén eigenmode (AE) activity and thermal transport. For neutral-beam-only heating, strong AE activity is observed that causes a ∼35% degradation in the neutron rate. With central ECCD this AE activity is suppressed, replaced by a bursty energetic particle mode that appears more benign as the neutron rate is closer to the classical value. Themore » electron thermal diffusivity increases by ≈50% for 2.4 MW of ECCD compared to neutral-beam-only cases. Fortunately, the global thermal confinement factor remains the same (H{sub 98y2}=1.4) as the higher thermal transport for P{sub EC}=2.4 MW hybrids is offset by the decreased fast ion transport resulting from AE suppression.« less

Grasp and index finger reach zone during one-handed smartphone rear interaction: effects of task type, phone width and hand length.

PubMed

Lee, Songil; Kyung, Gyouhyung; Lee, Jungyong; Moon, Seung Ki; Park, Kyoung Jong

2016-11-01

Recently, some smartphones have introduced index finger interaction functions on the rear surface. The current study investigated the effects of task type, phone width, and hand length on grasp, index finger reach zone, discomfort, and muscle activation during such interaction. We considered five interaction tasks (neutral, comfortable, maximum, vertical, and horizontal strokes), two device widths (60 and 90 mm) and three hand lengths. Horizontal (vertical) strokes deviated from the horizontal axis in the range from -10.8° to -13.5° (81.6-88.4°). Maximum strokes appeared to be excessive as these caused 43.8% greater discomfort than did neutral strokes. The 90-mm width also appeared to be excessive as it resulted in 12.3% increased discomfort relative to the 60-mm width. The small-hand group reported 11.9-18.2% higher discomfort ratings, and the percent maximum voluntary exertion of their flexor digitorum superficialis muscle, pertaining to index finger flexion, was also 6.4% higher. These findings should be considered to make smartphone rear interaction more comfortable. Practitioner Summary: Among neutral, comfortable, maximum, horizontal, and vertical index finger strokes on smartphone rear surfaces, maximum vs. neutral strokes caused 43.8% greater discomfort. Horizontal (vertical) strokes deviated from the horizontal (vertical) axis. Discomfort increased by 12.3% with 90-mm- vs. 60-mm-wide devices. Rear interaction regions of five commercialised smartphones should be lowered 20 to 30 mm for more comfortable rear interaction.

Prevalence of rotavirus antibodies in breast milk and inhibitory effects to rotavirus vaccines.

PubMed

Trang, Nguyen V; Braeckman, Tessa; Lernout, Tinne; Hau, Vu T B; Anh, Le T K; Luan, Le T; Van Damme, Pierre; Anh, Dang D

2014-01-01

Rotavirus (RV) is the most common cause of childhood diarrhea worldwide, and several vaccines have been successfully developed to reduce the burden of disease. However, lower vaccine immunogenicity and efficacy in developing countries might be related to the virus-neutralizing activity of breast milk. We examined possible differences in breast milk antibody levels (total IgA antibody, RV-specific antibodies, and RV-neutralizing antibodies) between healthy mothers living in a rural area (n=145) and mothers living in an urban area (n=147) of Vietnam. Total IgA concentration was significantly higher in samples from mothers in the rural region than in samples from mothers in the urban region, whereas urban mothers had significantly higher RV-specific IgA antibody titers than did rural mothers. Neutralizing antibodies against RV strain G1P[8] were undetected in nearly one-half of the breast milk samples (45-48%), whereas the majority of the remaining samples had low antibody titers (2-16). Despite these low titers, the breast milk still reduced vaccine strain titers (2×10(6) plaque forming units/mL) up to 80% or more, even at a milk-to-virus ratio of 1:8. An increase in neutralizing anti-G1P[8] antibody titers (P<0.05) in rural infants over time suggests a continuous exposure to circulating RV. These results contribute to the understanding of the potential interference of breast milk with RV vaccine efficacy and immunogenicity in Vietnamese infants.

(Evaluation of neutralizing ability of four commercially available antivenoms against the venom of Bothrops asper from Costa Rica)

PubMed

Bogarín, G; Segura, E; Durán, G; Lomonte, B; Rojas, G; Gutiérrez, J M

1995-09-01

We studied the ability of four commercially available antivenoms to neutralize several toxic and enzymatic activities of Bothrops asper (terciopelo) venom from Costa Rica. Experiments with preincubation of venom and antivenom were carried out to test the neutralization of lethal, hemorrhagic, coagulant and indirect hemolytic activities. In addition, antibody titers against crude venom and myotoxin II purified from this venom were determined by enzyme immunoassay (ELISA). Results indicate that polyvalent antivenom from Instituto Clodomiro Picado (Costa Rica) has the highest neutralizing ability against lethal, coagulant and indirect hemolytic activities, whereas MYN polyvalent antivenom (México) has the highest neutralization against hemorrhagic activity. Antivenom from Instituto Clodomiro Picado also has the highest antibody titers against crude B. asper venom and against myotoxin II. Antivenoms from Universidad Central de Venezuela (Venezuela), Vencofarma (Brazil) and MYN (México) failed to neutralize the lethal effect of this venom. These results stress the need for rigorous quality control systems to evaluate the neutralizing ability of antivenoms in Central America.

Emotional facial expressions differentially influence predictions and performance for face recognition.

PubMed

Nomi, Jason S; Rhodes, Matthew G; Cleary, Anne M

2013-01-01

This study examined how participants' predictions of future memory performance are influenced by emotional facial expressions. Participants made judgements of learning (JOLs) predicting the likelihood that they would correctly identify a face displaying a happy, angry, or neutral emotional expression in a future two-alternative forced-choice recognition test of identity (i.e., recognition that a person's face was seen before). JOLs were higher for studied faces with happy and angry emotional expressions than for neutral faces. However, neutral test faces with studied neutral expressions had significantly higher identity recognition rates than neutral test faces studied with happy or angry expressions. Thus, these data are the first to demonstrate that people believe happy and angry emotional expressions will lead to better identity recognition in the future relative to neutral expressions. This occurred despite the fact that neutral expressions elicited better identity recognition than happy and angry expressions. These findings contribute to the growing literature examining the interaction of cognition and emotion.

Reduction of selenite to elemental selenium nanoparticles by activated sludge.

PubMed

Jain, Rohan; Matassa, Silvio; Singh, Satyendra; van Hullebusch, Eric D; Esposito, Giovanni; Lens, Piet N L

2016-01-01

Total selenium removal by the activated sludge process, where selenite is reduced to colloidal elemental selenium nanoparticles (BioSeNPs) that remain entrapped in the activated sludge flocs, was studied. Total selenium removal efficiencies with glucose as electron donor (2.0 g chemical oxygen demand (COD) L(-1)) at neutral pH and 30 °C gave 2.9 and 6.8 times higher removal efficiencies as compared to the electron donors lactate and acetate, respectively. Total selenium removal efficiencies of 79 (±3) and 86 (±1) % were achieved in shake flasks and fed batch reactors, respectively, at dissolved oxygen (DO) concentrations above 4.0 mg L(-1) and 30 °C when fed with 172 mg L(-1) (1 mM) Na2SeO3 and 2.0 g L(-1) COD of glucose. Continuously operated reactors operating at neutral pH, 30 °C and a DO >3 mg L(-1) removed 33.98 and 36.65 mg of total selenium per gram of total suspended solids (TSS) at TSS concentrations of 1.3 and 3.0 g L(-1), respectively. However, selenite toxicity to the activated sludge led to failure of a continuously operating activated sludge reactor at the applied loading rates. This suggests that a higher hydraulic retention time (HRT) or different reactor configurations need to be applied for selenium-removing activated sludge processes. Graphical Abstract Scheme representing the possible mechanisms of selenite reduction at high and low DO levels in the activated sludge process.

Neutralization of venoms from two Southern Pacific Rattlesnakes (Crotalus helleri) with commercial antivenoms and endothermic animal sera.

PubMed

Galán, Jacob A; Sánchez, Elda E; Rodríguez-Acosta, Alexis; Pérez, John C

2004-06-01

The Southern Pacific Rattlesnake (Crotalus helleri) is found in southwestern California (USA), southward through north Baja California (MX) into the northern part of southern Baja California (MX). In this study, the venoms from two Southern Pacific Rattlesnakes were characterized. The two venoms were different in color, concentration, and enzyme activities. Two commercial antivenoms neutralized both C. helleri venoms differently. Antivipmyn (Fab2H) and CroFab (FabO) neutralized both venoms but had different ED50. Four times more Fab2H antivenom was required to neutralize the C. helleri venom No. 011-084-009 than the venom from the snake No. 010-367-284. The hemorrhagic activity of two C. helleri venoms were neutralized differently by endothermic animal sera having a natural resistance to hemorrhagic activity of snake venoms. Opossums and Mexican ground squirrel sera did not neutralize the hemorrhagic activity of the venom No. 010-367-284. The sera of gray woodrats and hispid cotton rats neutralized all hemorrhagins in both C. helleri venoms. This is the first reported case in which opossum serum has not neutralized hemorrhagic activity of pit viper venom. Differences in the compositions of C. helleri venoms and their ability to be neutralized may help explain why snakebites are a difficult medical problem to treat and why effective polyvalent antivenoms are difficult to produce.

Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response.

PubMed

Nitschke, Jack B; Sarinopoulos, Issidoros; Oathes, Desmond J; Johnstone, Tom; Whalen, Paul J; Davidson, Richard J; Kalin, Ned H

2009-03-01

The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response

PubMed Central

Nitschke, Jack B.; Sarinopoulos, Issidoros; Oathes, Desmond J.; Johnstone, Tom; Whalen, Paul J.; Davidson, Richard J.; Kalin, Ned H.

2009-01-01

Objective The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Method Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Results Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. Conclusions These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder. PMID:19122007

Purification and characterization of a trehalase-invertase enzyme with dual activity from Candida utilis.

PubMed

Lahiri, Sagar; Basu, Arghya; Sengupta, Shinjinee; Banerjee, Shakri; Dutta, Trina; Soren, Dhananjay; Chattopadhyay, Krishnananda; Ghosh, Anil K

2012-06-15

Trehalose and sucrose, two important anti-stress non-reducing natural disaccharides, are catabolized by two enzymes, namely trehalase and invertase respectively. In this study, a 175 kDa enzyme protein active against both substrates was purified from wild type Candida utilis and characterized in detail. Substrate specificity assay and activity staining revealed the enzyme to be specific for both sucrose and trehalose. The ratio between trehalase and invertase activity was found to be constant at 1:3.5 throughout the entire study. Almost 40-fold purification and 30% yield for both activities were achieved at the final step of purification. The presence of common enzyme inhibitors, thermal and pH stress had analogous effects on its trehalase and invertase activity. Km values for two activities were similar while Vmax and Kcat also differed by a factor of 3.5. Competition plot for both substrates revealed the two activities to be occurring at the single active site. N-terminal sequencing and MALDI-TOF data analysis revealed higher similarity of the purified protein to previously known neutral trehalases. While earlier workers mentioned independent purification of neutral trehalase or invertase from different sources, the present study reports the purification of a single protein showing dual activity. Copyright © 2012 Elsevier Inc. All rights reserved.

A novel, colorimetric neutralization assay for measuring antibodies to influenza viruses.

PubMed

Lehtoranta, Liisa; Villberg, Anja; Santanen, Riitta; Ziegler, Thedi

2009-08-01

A colorimetric cell proliferation assay for measuring neutralizing antibodies to influenza viruses in human sera is described. Following a 90-min incubation, the serum-virus mixture was transferred to Madin-Darby canine kidney cells cultured in 96-well plates. After further incubation for three days, a tetrazolium salt was added to the wells. Cellular mitochondrial dehydrogenases cleave the tetrazolium salt to formazan, and the resulting color change is read by a spectrophotometer. The absorbance values correlate directly to the number of viable cells in the assay well and thus also to the neutralizing activity of influenza-specific antibodies present in the serum. With the few hands-on manipulations required, this assay allows simultaneous testing of a considerable number of sera, offers opportunities for automation, and is suitable for use under biosafety level-3 conditions. The test was used to study the antibody response after the administration of seasonal, inactivated, trivalent influenza vaccine. Antibody titers determined by the neutralization test in pre- and post-vaccination serum pairs were compared with those obtained by the hemagglutination inhibition assay. The neutralization test yielded higher pre- and post-vaccination titers and a larger number of significant increases in post-vaccination antibody titer than the hemagglutination inhibition test. This new test format could serve as a valuable laboratory tool for influenza vaccine studies.

Separation of Acids, Bases, and Neutral Compounds

NASA Astrophysics Data System (ADS)

Fujita, Megumi; Mah, Helen M.; Sgarbi, Paulo W. M.; Lall, Manjinder S.; Ly, Tai Wei; Browne, Lois M.

2003-01-01

Separation of Acids, Bases, and Neutral Compounds requires the following software, which is available for free download from the Internet: Netscape Navigator, version 4.75 or higher, or Microsoft Internet Explorer, version 5.0 or higher; Chime plug-in, version compatible with your OS and browser (available from MDL); and Flash player, version 5 or higher (available from Macromedia).

Induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea.

PubMed

Ayoub, Shereen; Melzig, Matthias F

2006-04-01

Deposition of amyloid beta-peptide as senile plaques in the brain is one of the neuropathological hallmarks of Alzheimer's disease, which is the most prevalent progressive neurodegenerative disease leading to dementia. Neutral endopeptidase is one of the major beta-amyloid-degrading enzymes in the brain. To examine the influence of different polyphenols and other natural products from green tea extract (from Camellia sinensis, Theaceae), we used the neuroblastoma cell line SK-N-SH and studied the changes in the specific cellular neutral endopeptidase activity after long-term treatment with these substances. We have shown that caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. We have also shown that the combination of epicatechin, epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induced cellular neutral endopeptidase activity. It is suggested that the enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate.

Oscillation of certain higher-order neutral partial functional differential equations.

PubMed

Li, Wei Nian; Sheng, Weihong

2016-01-01

In this paper, we study the oscillation of certain higher-order neutral partial functional differential equations with the Robin boundary conditions. Some oscillation criteria are established. Two examples are given to illustrate the main results in the end of this paper.

Priming the Secure Attachment Schema Affects the Emotional Face Processing Bias in Attachment Anxiety: An fMRI Research

PubMed Central

Tang, Qingting; Chen, Xu; Hu, Jia; Liu, Ying

2017-01-01

Our study explored how priming with a secure base schema affects the processing of emotional facial stimuli in individuals with attachment anxiety. We enrolled 42 undergraduate students between 18 and 27 years of age, and divided them into two groups: attachment anxiety and attachment secure. All participants were primed under two conditions, the secure priming using references to the partner, and neutral priming using neutral references. We performed repeated attachment security priming combined with a dual-task paradigm and functional magnetic resonance imaging. Participants’ reaction times in terms of responding to the facial stimuli were also measured. Attachment security priming can facilitate an individual’s processing of positive emotional faces; for instance, the presentation of the partner’s name was associated with stronger activities in a wide range of brain regions and faster reaction times for positive facial expressions in the subjects. The current finding of higher activity in the left-hemisphere regions for secure priming rather than neutral priming is consistent with the prediction that attachment security priming triggers the spread of the activation of a positive emotional state. However, the difference in brain activity during processing of both, positive and negative emotional facial stimuli between the two priming conditions appeared in the attachment anxiety group alone. This study indicates that the effect of attachment secure priming on the processing of emotional facial stimuli could be mediated by chronic attachment anxiety. In addition, it highlights the association between higher-order processes of the attachment system (secure attachment schema priming) and early-stage information processing system (attention), given the increased attention toward the effects of secure base schema on the processing of emotion- and attachment-related information among the insecure population. Thus, the following study has applications in providing directions for clinical treatment of mood disorders in attachment anxiety. PMID:28473796

Priming the Secure Attachment Schema Affects the Emotional Face Processing Bias in Attachment Anxiety: An fMRI Research.

PubMed

Tang, Qingting; Chen, Xu; Hu, Jia; Liu, Ying

2017-01-01

Our study explored how priming with a secure base schema affects the processing of emotional facial stimuli in individuals with attachment anxiety. We enrolled 42 undergraduate students between 18 and 27 years of age, and divided them into two groups: attachment anxiety and attachment secure. All participants were primed under two conditions, the secure priming using references to the partner, and neutral priming using neutral references. We performed repeated attachment security priming combined with a dual-task paradigm and functional magnetic resonance imaging. Participants' reaction times in terms of responding to the facial stimuli were also measured. Attachment security priming can facilitate an individual's processing of positive emotional faces; for instance, the presentation of the partner's name was associated with stronger activities in a wide range of brain regions and faster reaction times for positive facial expressions in the subjects. The current finding of higher activity in the left-hemisphere regions for secure priming rather than neutral priming is consistent with the prediction that attachment security priming triggers the spread of the activation of a positive emotional state. However, the difference in brain activity during processing of both, positive and negative emotional facial stimuli between the two priming conditions appeared in the attachment anxiety group alone. This study indicates that the effect of attachment secure priming on the processing of emotional facial stimuli could be mediated by chronic attachment anxiety. In addition, it highlights the association between higher-order processes of the attachment system (secure attachment schema priming) and early-stage information processing system (attention), given the increased attention toward the effects of secure base schema on the processing of emotion- and attachment-related information among the insecure population. Thus, the following study has applications in providing directions for clinical treatment of mood disorders in attachment anxiety.

Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine.

PubMed

Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan; Xu, Jianqing

2012-01-01

A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.

Recruitment of Language-, Emotion- and Speech-Timing Associated Brain Regions for Expressing Emotional Prosody: Investigation of Functional Neuroanatomy with fMRI

PubMed Central

Mitchell, Rachel L. C.; Jazdzyk, Agnieszka; Stets, Manuela; Kotz, Sonja A.

2016-01-01

We aimed to progress understanding of prosodic emotion expression by establishing brain regions active when expressing specific emotions, those activated irrespective of the target emotion, and those whose activation intensity varied depending on individual performance. BOLD contrast data were acquired whilst participants spoke non-sense words in happy, angry or neutral tones, or performed jaw-movements. Emotion-specific analyses demonstrated that when expressing angry prosody, activated brain regions included the inferior frontal and superior temporal gyri, the insula, and the basal ganglia. When expressing happy prosody, the activated brain regions also included the superior temporal gyrus, insula, and basal ganglia, with additional activation in the anterior cingulate. Conjunction analysis confirmed that the superior temporal gyrus and basal ganglia were activated regardless of the specific emotion concerned. Nevertheless, disjunctive comparisons between the expression of angry and happy prosody established that anterior cingulate activity was significantly higher for angry prosody than for happy prosody production. Degree of inferior frontal gyrus activity correlated with the ability to express the target emotion through prosody. We conclude that expressing prosodic emotions (vs. neutral intonation) requires generic brain regions involved in comprehending numerous aspects of language, emotion-related processes such as experiencing emotions, and in the time-critical integration of speech information. PMID:27803656

Visual Aversive Learning Compromises Sensory Discrimination.

PubMed

Shalev, Lee; Paz, Rony; Avidan, Galia

2018-03-14

Aversive learning is thought to modulate perceptual thresholds, which can lead to overgeneralization. However, it remains undetermined whether this modulation is domain specific or a general effect. Moreover, despite the unique role of the visual modality in human perception, it is unclear whether this aspect of aversive learning exists in this modality. The current study was designed to examine the effect of visual aversive outcomes on the perception of basic visual and auditory features. We tested the ability of healthy participants, both males and females, to discriminate between neutral stimuli, before and after visual learning. In each experiment, neutral stimuli were associated with aversive images in an experimental group and with neutral images in a control group. Participants demonstrated a deterioration in discrimination (higher discrimination thresholds) only after aversive learning. This deterioration was measured for both auditory (tone frequency) and visual (orientation and contrast) features. The effect was replicated in five different experiments and lasted for at least 24 h. fMRI neural responses and pupil size were also measured during learning. We showed an increase in neural activations in the anterior cingulate cortex, insula, and amygdala during aversive compared with neutral learning. Interestingly, the early visual cortex showed increased brain activity during aversive compared with neutral context trials, with identical visual information. Our findings imply the existence of a central multimodal mechanism, which modulates early perceptual properties, following exposure to negative situations. Such a mechanism could contribute to abnormal responses that underlie anxiety states, even in new and safe environments. SIGNIFICANCE STATEMENT Using a visual aversive-learning paradigm, we found deteriorated discrimination abilities for visual and auditory stimuli that were associated with visual aversive stimuli. We showed increased neural activations in the anterior cingulate cortex, insula, and amygdala during aversive learning, compared with neutral learning. Importantly, similar findings were also evident in the early visual cortex during trials with aversive/neutral context, but with identical visual information. The demonstration of this phenomenon in the visual modality is important, as it provides support to the notion that aversive learning can influence perception via a central mechanism, independent of input modality. Given the dominance of the visual system in human perception, our findings hold relevance to daily life, as well as imply a potential etiology for anxiety disorders. Copyright © 2018 the authors 0270-6474/18/382766-14$15.00/0.

The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals.

PubMed

Kohler, Ines; Kouyos, Roger; Bianchi, Matteo; Grube, Christina; Wyrzucki, Arkadiusz; Günthard, Huldrych F; Hangartner, Lars

2015-09-10

HIV-positive individuals have lower antibody titers to influenza viruses than HIV-negative individuals, and the benefits of the annual vaccinations are controversially discussed. Also, there is no information about the breadth of the antibody response in HIV-infected individuals. The binding and neutralizing antibody titers to various human and nonhuman influenza A virus strain were determined in sera from 146 HIV-infected volunteers: They were compared with those found in 305 randomly selected HIV-negative donors, and put in relation to HIV-specific parameters. Univariable and multivariable regression was used to identify HIV-specific parameters associated with the measured binding and neutralizing activity. Enzyme-linked immunosorbent assays and in-vitro neutralization assays were used to determine the binding and neutralizing antibodiy titers to homo and heterosubtypic influenza A subtypes. We found that both homo and heterosubtypic antibody titers are lower in HIV-positive individuals. Vaccination promoted higher binding and neutralizing antibody titers to human but not to nonhuman isolates. HIV-induced immune damage (high viral load, low CD4 T-cell counts, and long untreated disease progression) is associated with impaired homosubtypic responses, but can have beneficial effects on the development of heterosubtypic antibodies, and an improved ratio of binding to neutralizing antibody titers to homosubtypic isolates. Our results indicate that repetitive vaccinations in HIV-positive individuals enhance antibody titers to human isolates. Interestingly, development of antibody titers to conserved heterosubtypic epitopes paradoxically appeared to profit from HIV-induced immune damage, as did the ratio of binding to neutralizing antibodies.

Atypical parietal lobe activity to subliminal faces in youth with a family history of alcoholism

PubMed Central

Peraza, Jennifer; Cservenka, Anita; Herting, Megan M.; Nagel, Bonnie J.

2015-01-01

Background Adults with alcohol use disorders (AUDs) show different behavioral and neurological functioning during emotional processing tasks from healthy controls. Adults with a family history (FHP) of AUD also show different activation in limbic brain areas, such as the amygdala. However, it is unclear if this pattern exists during adolescence before any episodes of heavy alcohol use. Objectives We hypothesized that the amygdalar response to subliminally-presented fearful faces would be reduced in FHP adolescents compared to peers who were family history negative (FHN) for AUD. Method An adapted Masked Faces paradigm was used to examine blood oxygen level-dependent response to subliminal fearful vs. neutral faces in 14 FHP (6 females, 8 males) and 15 FHN (6 females, 9 males) youth, ages 11–15 years. Both FHP and FHN youth had no history of heavy alcohol consumption. Results A significant difference was seen between groups in the left superior parietal lobule FHN youth showed deactivation to fearful and neutral masked faces compared to baseline, whereas FHP youth showed deactivation only to fearful masked faces. No significant differences in amygdalar activation were seen between groups. Conclusion The left superior parietal lobule is part of the fronto-parietal network, which has been implicated in attentional control. Lack of reduced neural activity to neutral faces among FHP youth may represent differences in suppressing attention networks to less salient emotional stimuli, or perhaps, a higher threshold of saliency for emotional stimuli among at-risk youth. PMID:25268683

Atypical parietal lobe activity to subliminal faces in youth with a family history of alcoholism.

PubMed

Peraza, Jennifer; Cservenka, Anita; Herting, Megan M; Nagel, Bonnie J

2015-03-01

Adults with alcohol use disorders (AUDs) show different behavioral and neurological functioning during emotional processing tasks from healthy controls. Adults with a family history (FHP) of AUD also show different activation in limbic brain areas, such as the amygdala. However, it is unclear if this pattern exists during adolescence before any episodes of heavy alcohol use. We hypothesized that the amygdalar response to subliminally-presented fearful faces would be reduced in FHP adolescents compared to peers who were family history negative (FHN) for AUD. An adapted Masked Faces paradigm was used to examine blood oxygen level-dependent response to subliminal fearful vs. neutral faces in 14 FHP (6 females, 8 males) and 15 FHN (6 females, 9 males) youth, ages 11-15 years. Both FHP and FHN youth had no history of heavy alcohol consumption. A significant difference was seen between groups in the left superior parietal lobule FHN youth showed deactivation to fearful and neutral masked faces compared to baseline, whereas FHP youth showed deactivation only to fearful masked faces. No significant differences in amygdalar activation were seen between groups. The left superior parietal lobule is part of the fronto-parietal network, which has been implicated in attentional control. Lack of reduced neural activity to neutral faces among FHP youth may represent differences in suppressing attention networks to less salient emotional stimuli, or perhaps, a higher threshold of saliency for emotional stimuli among at-risk youth.

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

NASA Astrophysics Data System (ADS)

Pace, D. C.; Austin, M. E.; Bardoczi, L.; Collins, C. S.; Crowley, B.; Davis, E.; Du, X.; Ferron, J.; Grierson, B. A.; Heidbrink, W. W.; Holcomb, C. T.; McKee, G. R.; Pawley, C.; Petty, C. C.; Podestà, M.; Rauch, J.; Scoville, J. T.; Spong, D. A.; Thome, K. E.; Van Zeeland, M. A.; Varela, J.; Victor, B.

2018-05-01

An engineering upgrade to the neutral beam system at the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)] enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic ( E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2 MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities and results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

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

Austin, Max E.; Bardoczi, Laszlo; Collins, Cami S.

Here, an engineering upgrade to the neutral beam system at the DIII-D tokamak enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic (E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities andmore » results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.« less

Dynamic neutral beam current and voltage control to improve beam efficacy in tokamaks

DOE PAGES

Austin, Max E.; Bardoczi, Laszlo; Collins, Cami S.; ...

2018-04-20

Here, an engineering upgrade to the neutral beam system at the DIII-D tokamak enables time-dependent programming of the beam voltage and current. Initial application of this capability involves pre-programmed beam voltage and current injected into plasmas that are known to be susceptible to instabilities that are driven by energetic (E ≥ 40 keV) beam ions. These instabilities, here all Alfvén eigenmodes (AEs), increase the transport of the beam ions beyond a classical expectation based on particle drifts and collisions. Injecting neutral beam power, P beam ≥ 2MW, at reduced voltage with increased current reduces the drive for Alfvénic instabilities andmore » results in improved ion confinement. In lower-confinement plasmas, this technique is applied to eliminate the presence of AEs across the mid-radius of the plasmas. Simulations of those plasmas indicate that the mode drive is decreased and the radial extent of the remaining modes is reduced compared to a higher beam voltage case. In higher-confinement plasmas, this technique reduces AE activity in the far edge and results in an interesting scenario of beam current drive improving as the beam voltage reduces from 80 kV to 65 kV.« less

Isolation, Purification, Characterization and Effect upon HepG2 Cells of Anemaran from Rhizome Anemarrhena.

PubMed

Jiang, Qian-Qian; Zhao, Yun-Ping; Gao, Wen-Yuan; Li, Xia; Huang, Lu-Qi; Xiao, Pei-Gen

2013-01-01

The rhizome of Anemarrhena asphodeloides is used as food and traditional Chinese medicine for its hypoglycemic effect. The aim of this study was to investigate the isolation, purification and hypoglycemic activity of Anemaran as the active component. The influence factors (isolation duration, ratio of residuals to water and extracting times) during the isolation process were evaluated. The optimal conditions for NA and AA were extraction temperature 90ºC and 100ºC, duration 1h and 1.5 h, extraction time 3 and 3, and the solid-liquor ratio 1:20 and 1:15, respectively. Neutral and acid Anemaran (NA and AA) were isolated from the rhizome of Anemarrhena asphodeloides. Five fractions of NA-1, NA-2, NA-3, AA-1 and AA-2 were obtained after crude neutral and acid Anemaran purified through DEAE- 52 cellulose anion-exchange column. The characterizations of Anemaran and its different fractions were both analyzed by Fourier transform infrared spectroscopy (FT-IR) and scanning electron micrographs (SEM). Structural properties of different fractions were examined by FT-IR. Strong characteristic absorption peaks were observed at around 1744 cm(-1)and 1650 cm(-1) caused by the C=O group of uronic acids, and the band between 1440 cm(-1) and 1395 cm(-1) associated with the stretching vibration of C-O of galacturonic acid. Neither the crude neutral, nor the acid anemaran significantly inhibited the growth of HepG2 cells in-vitro, which indicated the low cytotoxicity of the anemaran. Furthermore, both neutral and acid anemaran showed hypoglycemic effect. The hypoglycemic effect of neutral anemaran was much higher than that of acid anemaran.

Electric-current Neutralization, Magnetic Shear, and Eruptive Activity in Solar Active Regions

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

Liu, Yang; Sun, Xudong; Török, Tibor

The physical conditions that determine whether or not solar active regions (ARs) produce strong flares and coronal mass ejections (CMEs) are not yet well understood. Here, we investigate the association between electric-current neutralization, magnetic shear along polarity inversion lines (PILs), and eruptive activity in four ARs: two emerging and two well-developed ones. We find that the CME-producing ARs are characterized by a strongly non-neutralized total current, while the total current in the ARs that did not produce CMEs is almost perfectly neutralized. The difference in the PIL shear between these two groups is much less pronounced, which suggests that themore » degree of current neutralization may serve as a better proxy for assessing the ability of ARs to produce CMEs.« less

Influence of emotional valence and arousal on the spread of activation in memory.

PubMed

Jhean-Larose, Sandra; Leveau, Nicolas; Denhière, Guy

2014-11-01

Controversy still persists on whether emotional valence and arousal influence cognitive activities. Our study sought to compare how these two factors foster the spread of activation within the semantic network. In a lexical decision task, prime words were varied depending on the valence (pleasant or unpleasant) or on the level of emotional arousal (high or low). Target words were carefully selected to avoid semantic priming effects, as well as to avoid arousing specific emotions (neutral). Three SOA durations (220, 420 and 720 ms) were applied across three independent groups. Results indicate that at 220 ms, the effect of arousal is significantly higher than the effect of valence in facilitating spreading activation while at 420 ms, the effect of valence is significantly higher than the effect of arousal in facilitating spreading activation. These findings suggest that affect is a sequential process involving the successive intervention of arousal and valence.

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against different Lyssavirus species.

PubMed

Malerczyk, Claudius; Freuling, Conrad; Gniel, Dieter; Giesen, Alexandra; Selhorst, Thomas; Müller, Thomas

2014-01-01

Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2. Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV. Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate). Cross-neutralizing activities partly correlate with the phylogenetic distance of the virus species. Cross-neutralizing activities against the species BBLV and DUVV of phylogroup 1 were demonstrated, in line with previous results of cross-neutralizing activities against ABLV and EBLV-1 and -2. Potential partial cross-neutralizing activities against more distant lyssavirus species like selected MOKV strains need further research.

Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training☆☆☆

PubMed Central

Hölzel, Britta K.; Hoge, Elizabeth A.; Greve, Douglas N.; Gard, Tim; Creswell, J. David; Brown, Kirk Warren; Barrett, Lisa Feldman; Schwartz, Carl; Vaitl, Dieter; Lazar, Sara W.

2013-01-01

Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala–prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala–prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements. PMID:24179799

Stepwise Engineering of Heterodimeric Single Domain Camelid VHH Antibodies That Passively Protect Mice from Ricin Toxin*

PubMed Central

Vance, David J.; Tremblay, Jacqueline M.; Mantis, Nicholas J.; Shoemaker, Charles B.

2013-01-01

In an effort to engineer countermeasures for the category B toxin ricin, we produced and characterized a collection of epitopic tagged, heavy chain-only antibody VH domains (VHHs) specific for the ricin enzymatic (RTA) and binding (RTB) subunits. Among the 20 unique ricin-specific VHHs we identified, six had toxin-neutralizing activity: five specific for RTA and one specific for RTB. Three neutralizing RTA-specific VHHs were each linked via a short peptide spacer to the sole neutralizing anti-RTB VHH to create VHH “heterodimers.” As compared with equimolar concentrations of their respective monovalent monomers, all three VHH heterodimers had higher affinities for ricin and, in the case of heterodimer D10/B7, a 6-fold increase in in vitro toxin-neutralizing activity. When passively administered to mice at a 4:1 heterodimer:toxin ratio, D10/B7 conferred 100% survival in response to a 10 × LD50 ricin challenge, whereas a 2:1 heterodimer:toxin ratio conferred 20% survival. However, complete survival was achievable when the low dose of D10/B7 was combined with an IgG1 anti-epitopic tag monoclonal antibody, possibly because decorating the toxin with up to four IgGs promoted serum clearance. The two additional ricin-specific heterodimers, when tested in vivo, provided equal or greater passive protection than D10/B7, thereby warranting further investigation of all three heterodimers as possible therapeutics. PMID:24202178

Stepwise engineering of heterodimeric single domain camelid VHH antibodies that passively protect mice from ricin toxin.

PubMed

Vance, David J; Tremblay, Jacqueline M; Mantis, Nicholas J; Shoemaker, Charles B

2013-12-20

In an effort to engineer countermeasures for the category B toxin ricin, we produced and characterized a collection of epitopic tagged, heavy chain-only antibody VH domains (VHHs) specific for the ricin enzymatic (RTA) and binding (RTB) subunits. Among the 20 unique ricin-specific VHHs we identified, six had toxin-neutralizing activity: five specific for RTA and one specific for RTB. Three neutralizing RTA-specific VHHs were each linked via a short peptide spacer to the sole neutralizing anti-RTB VHH to create VHH "heterodimers." As compared with equimolar concentrations of their respective monovalent monomers, all three VHH heterodimers had higher affinities for ricin and, in the case of heterodimer D10/B7, a 6-fold increase in in vitro toxin-neutralizing activity. When passively administered to mice at a 4:1 heterodimer:toxin ratio, D10/B7 conferred 100% survival in response to a 10 × LD50 ricin challenge, whereas a 2:1 heterodimer:toxin ratio conferred 20% survival. However, complete survival was achievable when the low dose of D10/B7 was combined with an IgG1 anti-epitopic tag monoclonal antibody, possibly because decorating the toxin with up to four IgGs promoted serum clearance. The two additional ricin-specific heterodimers, when tested in vivo, provided equal or greater passive protection than D10/B7, thereby warranting further investigation of all three heterodimers as possible therapeutics.

Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.

PubMed

Hwang, Ji-Sun; Jung, Eun-Hye; Kwon, Mi-Youn; Han, Inn-Oc

2016-09-15

We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment. Copyright © 2016. Published by Elsevier B.V.

Effects of dextromethorphan/quinidine on auditory event-related potentials in multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2009-10-01

The purpose of this study was to characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of laughing and/or crying in patients with multiple sclerosis before and after treatment with dextromethorphan/quinidine (DM/Q). Behavioral responses and event-related potentials (ERPs) in response to subjectively significant and neutral verbal stimuli were recorded from 2 groups: 6 multiple sclerosis patients with PBA before (PBA-preTx) and after (PBA-DM/Q) treatment with DM/Q and 6 healthy control (HC) subjects. Statistical nonparametric mapping comparisons of ERP source current density distributions between groups were conducted for subjectively significant and neutral stimuli separately before and after treatment with DM/Q. Treatment with DM/Q had a normalizing effect on the behavioral responses of PBA patients. Event-related potential waveform comparisons of PBA-preTx and PBA-DM/Q with HC, for both neutral and subjectively significant stimuli, revealed effects on early ERP components. Comparisons between PBA-preTx and HC, in response to subjectively significant stimuli, revealed both early and late effects. Source analysis comparisons between PBA-preTx and PBA-DM/Q indicated distinct activations in areas involved in emotional processing and high-level and associative visual processing in response to neutral stimuli and in areas involved in emotional, somatosensory, primary, and premotor processing in response to subjectively significant stimuli. In most cases, stimuli evoked higher current density in PBA-DM/Q compared with the other groups. In conclusion, differences in brain activity were observed before and after medication. Also, DM/Q administration resulted in normalization of behavioral and electrophysiological measures.

Neutralization, by a monospecific Bothrops lanceolatus antivenom, of toxic activities induced by homologous and heterologous Bothírops snake venoms.

PubMed

Bogarín, G; Romero, M; Rojas, G; Lutsch, C; Casadamont, M; Lang, J; Otero, R; Gutiérrez, J M

1999-03-01

A monospecific Bothrops lanceolatus antivenom, currently used in Martinique, was tested for its efficacy in the neutralization of several toxic and enzymatic activities of the venoms of B. lanceolatus, B. atrox and B. asper. When tested by the i.p. route in mice, B. lanceolatus venom had an LD50 of 12.8 microg/g. In addition, it induced local tissue damage (hemorrhage, edema and myotoxicity) and showed indirect hemolytic activity, but was devoid of coagulant effect on human plasma in vitro and of defibrinating activity in mice. Antivenom was fully effective in the neutralization of lethal, hemorrhagic, edema-forming, myotoxic and indirect hemolytic effects of B. lanceolatus venom in assays involving preincubation of venom and antivenom. When tested against the venoms of B. asper and B. atrox, the antivenom completely neutralized the lethal, hemorrhagic, myotoxic and indirect hemolytic effects, and was partially effective in neutralizing edema-forming activity. In contrast, the antivenom was ineffective in the neutralization of in vitro coagulant and in vivo defibrinating effects induced by these two venoms.

Jumping to conclusions and the continuum of delusional beliefs.

PubMed

Warman, Debbie M; Lysaker, Paul H; Martin, Joel M; Davis, Louanne; Haudenschield, Samantha L

2007-06-01

The present study examined the jumping to conclusions reasoning bias across the continuum of delusional ideation by investigating individuals with active delusions, delusion prone individuals, and non-delusion prone individuals. Neutral and highly self-referent probabilistic reasoning tasks were employed. Results indicated that individuals with delusions gathered significantly less information than delusion prone and non-delusion prone participants on both the neutral and self-referent tasks, (p<.001). Individuals with delusions made less accurate decisions than the delusion prone and non-delusion prone participants on both tasks (p<.001), yet were more confident about their decisions than were delusion prone and non-delusion prone participants on the self-referent task (p=.002). Those with delusions and those who were delusion prone reported higher confidence in their performance on the self-referent task than they did the neutral task (p=.02), indicating that high self-reference impacted information processing for individuals in both of these groups. The results are discussed in relation to previous research in the area of probabilistic reasoning and delusions.

Adjuvant effects and antiserum action potentiation by a (herbal) compound 2-hydroxy-4-methoxy benzoic acid isolated from the root extract of the Indian medicinal plant 'sarsaparilla' (Hemidesmus indicus R. Br.).

PubMed

Alam, M I; Gomes, A

1998-10-01

The adjuvant effect and antiserum potentiation of a compound 2-hydroxy-4-methoxy benzoic acid were explored in the present investigation. This compound, isolated and purified from the Indian medicinal plant Hemidesmus indicus R. Br, possessed antisnake venom activity. Rabbits immunized with Vipera russellii venom in the presence and absence of the compound along with Freund's complete adjuvant, produced a precipitating band in immunogel diffusion and immunogel electrophoresis. The venom neutralizing capacity of this antiserum showed positive adjuvant effects as evident by the higher neutralization capacity (lethal and hemorrhage) when compared with the antiserum raised with venom alone. The pure compound potentiated the lethal action neutralization of venom by commercial equine polyvalent snake venom antiserum in experimental models. These observations raised the possibility of the use of chemical antagonists (from herbs) against snake bite, which may provide a better protection in presence of antiserum, especially in the rural parts of India.

Direct Identification of Tyrosine Sulfation by using Ultraviolet Photodissociation Mass Spectrometry

NASA Astrophysics Data System (ADS)

Robinson, Michelle R.; Moore, Kevin L.; Brodbelt, Jennifer S.

2014-08-01

Sulfation is a common post-translational modification of tyrosine residues in eukaryotes; however, detection using traditional liquid chromatography-mass spectrometry (LC-MS) methods is challenging based on poor ionization efficiency in the positive ion mode and facile neutral loss upon collisional activation. In the present study, 193 nm ultraviolet photodissociation (UVPD) is applied to sulfopeptide anions to generate diagnostic sequence ions, which do not undergo appreciable neutral loss of sulfate even using higher energy photoirradiation parameters. At the same time, neutral loss of SO3 is observed from the precursor and charge-reduced precursor ions, a spectral feature that is useful for differentiating tyrosine sulfation from the nominally isobaric tyrosine phosphorylation. LC-MS detection limits for UVPD analysis in the negative mode were determined to be around 100 fmol for three sulfated peptides, caerulein, cionin, and leu-enkephalin. The LC-UVPD-MS method was applied for analysis of bovine fibrinogen, and its key sulfated peptide was confidently identified.

A large neutral fraction of cosmic hydrogen a billion years after the Big Bang.

PubMed

Wyithe, J Stuart B; Loeb, Abraham

2004-02-26

The fraction of ionized hydrogen left over from the Big Bang provides evidence for the time of formation of the first stars and quasar black holes in the early Universe; such objects provide the high-energy photons necessary to ionize hydrogen. Spectra of the two most distant known quasars show nearly complete absorption of photons with wavelengths shorter than the Lyman alpha transition of neutral hydrogen, indicating that hydrogen in the intergalactic medium (IGM) had not been completely ionized at a redshift of z approximately 6.3, about one billion years after the Big Bang. Here we show that the IGM surrounding these quasars had a neutral hydrogen fraction of tens of per cent before the quasar activity started, much higher than the previous lower limits of approximately 0.1 per cent. Our results, when combined with the recent inference of a large cumulative optical depth to electron scattering after cosmological recombination therefore suggest the presence of a second peak in the mean ionization history of the Universe.

Direct Identification of Tyrosine Sulfation by using Ultraviolet Photodissociation Mass Spectrometry

PubMed Central

Robinson, Michelle R.; Moore, Kevin L.; Brodbelt, Brodbelt

2014-01-01

Sulfation is a common post-translational modification of tyrosine residues in eukaryotes; however, detection using traditional liquid chromatography-mass spectrometry (LC-MS) methods is challenging based on poor ionization efficiency in the positive ion mode and facile neutral loss upon collisional activation. In the present study, 193 nm ultraviolet photodissociation (UVPD) is applied to sulfopeptide anions to generate diagnostic sequence ions which do not undergo appreciable neutral loss of sulfate even using higher energy photoirradiation parameters. At the same time, neutral loss of sulfate is observed from the precursor and charge reduced precursor ions, a spectral feature that is useful for differentiating tyrosine sulfation from the nominally isobaric tyrosine phosphorylation. LC-MS detection limits for UVPD analysis in the negative mode were determined to be around 100 fmol for three sulfated peptides, caerulein, cionin, and leu-enkephalin. The LC-UVPD-MS method was applied for analysis of bovine fibrinogen, and its key sulfated peptide was confidently identified. PMID:24845354

The neural fate of neutral information in emotion-enhanced memory.

PubMed

Watts, Sarah; Buratto, Luciano G; Brotherhood, Emilie V; Barnacle, Gemma E; Schaefer, Alexandre

2014-07-01

In this study, we report evidence that neural activity reflecting the encoding of emotionally neutral information in memory is reduced when neutral and emotional stimuli are intermixed during encoding. Specifically, participants studied emotional and neutral pictures organized in mixed lists (in which emotional and neutral pictures were intermixed) or in pure lists (only-neutral or only-emotional pictures) and performed a recall test. To estimate encoding efficiency, we used the Dm effect, measured with event-related potentials. Recall for neutral items was lower in mixed compared to pure lists and posterior Dm activity for neutral items was reduced in mixed lists, whereas it remained robust in pure lists. These findings might be caused by an asymmetrical competition for attentional and working memory resources between emotional and neutral information, which could be a major determinant of emotional memory effects. Copyright © 2014 Society for Psychophysiological Research.

[Effects of different catch modes on soil enzyme activities and bacterial community in the rhizosphere of cucumber].

PubMed

Li, Min; Wu, Feng-zhi

2014-12-01

Effects of different catch modes on soil enzyme activities and bacterial community in the rhizosphere of cucumber (Cucumis sativus) were analyzed by conventional chemical method, PCR-denaturing gradient gel electrophoresis (DGGE) and real-time PCR methods. Pot experiment was carried out in the greenhouse for three consecutive years with cucumber as the main crop, and scallion (Allium fistulosum), wheat (Triticum aestivum) and oilseed rape (Brassica campestri) as catch crops. Results showed that, with the increase of crop planting times, soil urease, neutral phosphatase and invertase activities in the wheat treatment were significantly) higher than in the scallion and oilseed rape treatments, and these enzyme activities in the oilseed rape treatment were significantly higher than in the scallion treatment. PCR-DGGR analysis showed that cucumber rhizosphere bacterial community structures were different among treatments. Scallion and wheat treatments maintained relatively higher diversity indices of bacterial community structure. qPCR results showed that the abundance of soil bacterial community in the wheat treatment was significantly higher than in the scallion and oilseed rape treatments. In conclusion, different catch treatments affected soil enzyme activities and bacteria community and changed the soil environment. Wheat used as summer catch crop could maintain relatively higher soil enzyme activities, bacterial community diversity and abundance.

Disentangling brain activity related to the processing of emotional visual information and emotional arousal.

PubMed

Kuniecki, Michał; Wołoszyn, Kinga; Domagalik, Aleksandra; Pilarczyk, Joanna

2018-05-01

Processing of emotional visual information engages cognitive functions and induces arousal. We aimed to examine the modulatory role of emotional valence on brain activations linked to the processing of visual information and those linked to arousal. Participants were scanned and their pupil size was measured while viewing negative and neutral images. The visual noise was added to the images in various proportions to parametrically manipulate the amount of visual information. Pupil size was used as an index of physiological arousal. We show that arousal induced by the negative images, as compared to the neutral ones, is primarily related to greater amygdala activity while increasing visibility of negative content to enhanced activity in the lateral occipital complex (LOC). We argue that more intense visual processing of negative scenes can occur irrespective of the level of arousal. It may suggest that higher areas of the visual stream are fine-tuned to process emotionally relevant objects. Both arousal and processing of emotional visual information modulated activity within the ventromedial prefrontal cortex (vmPFC). Overlapping activations within the vmPFC may reflect the integration of these aspects of emotional processing. Additionally, we show that emotionally-evoked pupil dilations are related to activations in the amygdala, vmPFC, and LOC.

Respiratory Syncytial Virus (RSV): Neutralizing Antibody, a Correlate of Immune Protection.

PubMed

Piedra, Pedro A; Hause, Anne M; Aideyan, Letisha

2016-01-01

Assays that measure RSV-specific neutralizing antibody activity are very useful for evaluating vaccine candidates, performing seroprevalence studies, and detecting infection. Neutralizing antibody activity is normally measured by a plaque reduction neutralization assay or by a microneutralization assay with or without complement. These assays measure the functional capacity of serum (or other fluids) to neutralize virus infectivity in cells as compared to ELISA assays that only measure the binding capacity against an antigen. This chapter discusses important elements in standardization of the RSV-specific microneutralization assay for use in the laboratory.

Structural Analysis of Charge Discrimination in the Binding of Inhibitors to Human Carbonic Anhydrases I and II

PubMed Central

Srivastava, D. K.; Jude, Kevin M.; Banerjee, Abir L.; Haldar, Manas; Manokaran, Sumathra; Kooren, Joel; Mallik, Sanku; Christianson, David W.

2008-01-01

Despite the similarity in the active site pockets of carbonic anhydrase (CA) isozymes I and II, the binding affinities of benzenesulfonamide inhibitors are invariably higher with CA II as compared to CA I. To explore the structural basis of this molecular recognition phenomenon, we have designed and synthesized simple benzenesulfonamide inhibitors substituted at the para position with positively-charged, negatively-charged, and neutral functional groups, and we have determined the affinities and X-ray crystal structures of their enzyme complexes. The para-substituents are designed to bind in the midsection of the 15 Å deep active site cleft, where interactions with enzyme residues and solvent molecules are possible. We find that a para-substituted positively-charged amino group is more poorly tolerated in the active site of CA I compared with CA II. In contrast, a para-substituted negatively-charged carboxylate substituent is tolerated equally well in the active sites of both CA isozymes. Notably, enzyme-inhibitor affinity increases upon neutralization of inhibitor charged groups by amidation or esterification. These results inform the design of short molecular linkers connecting the benzenesulfonamide group and a para-substituted tail group in “two-prong” CA inhibitors: an optimal linker segment will be electronically neutral, yet capable of engaging in at least some hydrogen bond interactions with protein residues and/or solvent. Microcalorimetric data reveal that inhibitor binding to CA I is enthalpically less favorable and entropically more favorable than inhibitor binding to CA II. This contrasting behavior may arise in part from differences in active site desolvation and the conformational entropy of inhibitor binding to each isozyme active site. PMID:17407288

Increased frequencies of CD8+CD57+ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

PubMed Central

Palmer, Christine D; Romero-Tejeda, Marisol; Scully, Eileen P; Lockhart, Ainsley; Seaman, Michael S; Goldenthal, Ariel; Piechocka-Trocha, Alicja; Walker, Bruce D; Chibnik, Lori B; Jost, Stephanie; Porichis, Filippos

2016-01-01

Introduction An effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions. The immunologic milieu associated with development of neutralizing antibody breadth remains to be fully defined. In this study, we sought to identify immunological signatures associated with neutralization breadth in HIV controllers. We applied an immune monitoring approach to analyze markers of T cell and myeloid cell activation by flow cytometry, comparing broad neutralizers with low- and non-neutralizers using multivariate and univariate analyses. Methods Antibody neutralization breadth was determined, and cryopreserved peripheral blood mononuclear cells were stained for T cell and myeloid cell activation markers. Subjects were grouped according to neutralization breadth, and T cell and myeloid cell activation was analyzed by partial least squares discriminant analysis to determine immune signatures associated with high neutralization breadth. Results We show that neutralization breadth in HIV viraemic controllers (VC) was strongly associated with increased frequencies of CD8+CD57+ T cells and that this association was independent of viral load, CD4 count and time since HIV diagnosis. Conclusions Our data show elevated frequencies of CD8+CD57+ T cells in VC who develop neutralization breadth against HIV. This immune signature could serve as a potential biomarker of neutralization breadth and should be further investigated in other HIV-positive cohorts and in HIV vaccine trials. PMID:27938646

The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids

PubMed Central

Jaeger, Frederick; McGuire, Erin; Fouda, Genevieve; Amos, Joshua; Barbas, Kimberly; Ohashi, Tomoo; Alam, S. Munir; Erickson, Harold; Permar, Sallie R.

2016-01-01

Tenascin-C (TNC) is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals. PMID:27182834

Hip position and sex differences in motor unit firing patterns of the vastus medialis and vastus medialis oblique in healthy individuals.

PubMed

Peng, Yi-Ling; Tenan, Matthew S; Griffin, Lisa

2018-06-01

Weakness of the vastus medialis oblique (VMO) has been proposed to explain the high prevalence of knee pain in female subjects. Clinicians commonly use exercises in an attempt to preferentially activate the VMO. Recently, our group found evidence to support clinical theory that the VMO is neurologically distinct from the vastus medialis (VM). However, the ability to voluntarily activate these muscle subsections is still disputed. The aim of this study was to determine if VM and VMO activation varies between sexes and if control of the two muscles is different between rehabilitation exercises. Thirteen men and 13 women performed isometric straight leg raises in two hip positions, neutral hip rotation and 30 degrees lateral hip rotation. Bipolar intramuscular fine-wire electrodes were inserted into the VM and VMO to obtain motor unit recruitment thresholds and initial firing rates at recruitment. Linear mixed models and Tukey post hoc tests were used to assess significant differences in 654 motor units. Women demonstrated faster motor unit firing rate at recruitment, 1.18 ± 0.56 Hz higher than men. Motor units fired 0.47 ± 0.19 Hz faster during neutral hip rotation compared with lateral hip rotation. The VMO motor units were recruited 2.92 ± 1.28% earlier than the VM. All motor units were recruited 3.74 ± 1.27% earlier during neutral hip rotation than lateral hip rotation. Thus the VM and the VMO can be activated differentially, and their motor unit recruitment properties are affected by sex and hip position. NEW & NOTEWORTHY This is the first study to reveal differential activation of the vastus medialis oblique from the vastus medialis in clinical exercise protocols. Our research group used fine-wire electrodes to examine EMG signals of the vastus medialis oblique and vastus medialis to avoid possible cross talk. We also consider the effect of sex on motor unit firing patterns because of higher prevalence of knee pain in women, and yet few studies evaluating the sex differences in neuromuscular control.

Induction of HIV Neutralizing Antibodies against the MPER of the HIV Envelope Protein by HA/gp41 Chimeric Protein-Based DNA and VLP Vaccines

PubMed Central

Ye, Ling; Wen, Zhiyuan; Dong, Ke; Wang, Xi; Bu, Zhigao; Zhang, Huizhong; Compans, Richard W.; Yang, Chinglai

2011-01-01

Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14) in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy. PMID:21625584

Viper and cobra venom neutralization by beta-sitosterol and stigmasterol isolated from the root extract of Pluchea indica Less. (Asteraceae).

PubMed

Gomes, A; Saha, Archita; Chatterjee, Ipshita; Chakravarty, A K

2007-09-01

We reported previously that the methanolic root extract of the Indian medicinal plant Pluchea indica Less. (Asteraceae) could neutralize viper venom-induced action [Alam, M.I., Auddy, B., Gomes, A., 1996. Viper venom neutralization by Indian medicinal plant (Hemidesmus indicus and P. indica) root extracts. Phytother. Res. 10, 58-61]. The present study reports the neutralization of viper and cobra venom by beta-sitosterol and stigmasterol isolated from the root extract of P. indica Less. (Asteraceae). The active fraction (containing the major compound beta-sitosterol and the minor compound stigmasterol) was isolated and purified by silica gel column chromatography and the structure was determined using spectroscopic analysis (EIMS, (1)H NMR, (13)C NMR). Anti-snake venom activity was studied in experimental animals. The active fraction was found to significantly neutralize viper venom-induced lethal, hemorrhagic, defibrinogenation, edema and PLA(2) activity. Cobra venom-induced lethality, cardiotoxicity, neurotoxicity, respiratory changes and PLA(2) activity were also antagonized by the active component. It potentiated commercial snake venom antiserum action against venom-induced lethality in male albino mice. The active fraction could antagonize venom-induced changes in lipid peroxidation and superoxide dismutase activity. This study suggests that beta-sitosterol and stigmasterol may play an important role, along with antiserum, in neutralizing snake venom-induced actions.

Valence and the development of immediate and long-term false memory illusions.

PubMed

Howe, Mark L; Candel, Ingrid; Otgaar, Henry; Malone, Catherine; Wimmer, Marina C

2010-01-01

Across five experiments we examined the role of valence in children's and adults' true and false memories. Using the Deese/Roediger-McDermott paradigm and either neutral or negative-emotional lists, both adults' (Experiment 1) and children's (Experiment 2) true recall and recognition was better for neutral than negative items, and although false recall was also higher for neutral items, false recognition was higher for negative items. The last three experiments examined adults' (Experiment 3) and children's (Experiments 4 and 5) 1-week long-term recognition of neutral and negative-emotional information. The results replicated the immediate recall and recognition findings from the first two experiments. More important, these experiments showed that although true recognition decreased over the 1-week interval, false recognition of neutral items remained unchanged whereas false recognition of negative-emotional items increased. These findings are discussed in terms of theories of emotion and memory as well as their forensic implications.

Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes

PubMed Central

2017-01-01

Camptothecin (CPT) selectively traps topoisomerase 1-DNA cleavable complexes (Top1cc) to promote anticancer activity. Here, we report the design and synthesis of a new class of neutral porphyrin derivative 5,10-bis(4-carboxyphenyl)-15, 20-bis(4-dimethylaminophenyl)porphyrin (compound 8) as a potent catalytic inhibitor of human Top1. In contrast to CPT, compound 8 reversibly binds with the free enzyme and inhibits the formation of Top1cc and promotes reversal of the preformed Top1cc with CPT. Compound 8 induced inhibition of Top1cc formation in live cells was substantiated by fluorescence recovery after photobleaching (FRAP) assays. We established that MCF7 cells treated with compound 8 trigger proteasome-mediated Top1 degradation, accumulate higher levels of reactive oxygen species (ROS), PARP1 cleavage, oxidative DNA fragmentation, and stimulate apoptotic cell death without stabilizing apoptotic Top1-DNA cleavage complexes. Finally, compound 8 shows anticancer activity by targeting cellular Top1 and preventing the enzyme from directly participating in the apoptotic process. PMID:29290109

How affective information from faces and scenes interacts in the brain

PubMed Central

Vandenbulcke, Mathieu; Sinke, Charlotte B. A.; Goebel, Rainer; de Gelder, Beatrice

2014-01-01

Facial expression perception can be influenced by the natural visual context in which the face is perceived. We performed an fMRI experiment presenting participants with fearful or neutral faces against threatening or neutral background scenes. Triangles and scrambled scenes served as control stimuli. The results showed that the valence of the background influences face selective activity in the right anterior parahippocampal place area (PPA) and subgenual anterior cingulate cortex (sgACC) with higher activation for neutral backgrounds compared to threatening backgrounds (controlled for isolated background effects) and that this effect correlated with trait empathy in the sgACC. In addition, the left fusiform gyrus (FG) responds to the affective congruence between face and background scene. The results show that valence of the background modulates face processing and support the hypothesis that empathic processing in sgACC is inhibited when affective information is present in the background. In addition, the findings reveal a pattern of complex scene perception showing a gradient of functional specialization along the posterior–anterior axis: from sensitivity to the affective content of scenes (extrastriate body area: EBA and posterior PPA), over scene emotion–face emotion interaction (left FG) via category–scene interaction (anterior PPA) to scene–category–personality interaction (sgACC). PMID:23956081

Protective effects of broadly neutralizing immunoglobulin against homologous and heterologous equine infectious anemia virus infection in horses with severe combined immunodeficiency.

PubMed

Taylor, Sandra D; Leib, Steven R; Wu, Wuwei; Nelson, Robert; Carpenter, Susan; Mealey, Robert H

2011-07-01

Using the equine infectious anemia virus (EIAV) lentivirus model system, we previously demonstrated protective effects of broadly neutralizing immune plasma in young horses (foals) with severe combined immunodeficiency (SCID). However, in vivo selection of a neutralization-resistant envelope variant occurred. Here, we determined the protective effects of purified immunoglobulin with more potent broadly neutralizing activity. Overall, protection correlated with the breadth and potency of neutralizing activity in vitro. Four of five SCID foals were completely protected against homologous challenge, while partial protection occurred following heterologous challenge. These results support the inclusion of broadly neutralizing antibodies in lentivirus control strategies.

Immunogenicity and protective efficacy of rotavirus VP8* fused to cholera toxin B subunit in a mouse model.

PubMed

Xue, Miaoge; Yu, Linqi; Jia, Lianzhi; Li, Yijian; Zeng, Yuanjun; Li, Tingdong; Ge, Shengxiang; Xia, Ningshao

2016-11-01

In attempts to develop recombinant subunit vaccines against rotavirus disease, it was previously shown that the N-terminal truncated VP8* protein, VP8-1 (aa26-231), is a good vaccine candidate when used for immunization in combination with Freund's adjuvant. However, this protein stimulated only weak immune response when aluminum hydroxide was used as an adjuvant. In this study, the nontoxic B subunit of cholera toxin (CTB) was employed as intra-molecular adjuvant to improve the immunogenicity of VP8-1. Both, the N-terminal and C-terminal fusion proteins, were purified to homogeneity, at which stage they formed pentamers, and showed significantly higher immunogenicity and protective efficacy than a VP8-1/aluminum hydroxide mixture in a mouse model. Compared to VP8-1-CTB, CTB-VP8-1 showed higher binding activity to both, GM1 and the conformation sensitive neutralizing monoclonal antibodies specific to VP8. More importantly, CTB-VP8-1 elicited higher titers of neutralizing antibodies and conferred higher protective efficacy than VP8-1-CTB. Therefore, the protein CTB-VP8-1, with enhanced immunogenicity and immunoprotectivity, could be considered as a viable candidate for further development of an alternative, replication-incompetent, parenterally administered vaccine against rotavirus disease.

Effects of salinity and sea salt type on egg activation, fertilization, buoyancy and early embryology of European eel, Anguilla anguilla.

PubMed

Sørensen, Sune Riis; Butts, Ian Anthony Ernest; Munk, Peter; Tomkiewicz, Jonna

2016-02-01

Improper activation and swelling of in vitro produced eggs of European eel, Anguilla anguilla, has been shown to negatively affect embryonic development and hatching. We investigated this phenomenon by examining the effects of salinity and sea salt type on egg dimensions, cell cleavage patterns and egg buoyancy. Egg diameter after activation, using natural seawater adjusted to different salinities, varied among female eels, but no consistent pattern emerged. Activation salinities between 30-40 practical salinity unit (psu) produced higher quality eggs and generally larger egg diameters. Chorion diameters reached maximal values of 1642 ± 8 μm at 35 psu. A positive relationship was found between egg neutral buoyancy and activation salinity. Nine salt types were investigated as activation and incubation media. Five of these types induced a substantial perivitelline space (PVS), leading to large egg sizes, while the remaining four salt types resulted in smaller eggs. All salt types except NaCl treatments led to high fertilization rates and had no effect on fertilization success as well as egg neutral buoyancies at 7 h post-fertilization. The study points to the importance of considering ionic composition of the media when rearing fish eggs and further studies are encouraged.

Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat

PubMed Central

Mak, I. T.; Kramer, J. H.; Chmielinska, J. J.; Khalid, M. H.; Landgraf, K. M.; Weglicki, W. B.

2013-01-01

Neutral endopeptidase (NEP), which degrades substance P (SP), may regulate neutrophil activation during Mg-deficiency (MgD). Male Sprague-Dawley rats (180g) were fed MgD (~50 mg Mg/kg) or Mg-sufficient (MgS, 608 mg Mg/kg) diets for 7 days ± NEP inhibitor phosphoramidon (PR, 5 mg/kg/day, s. c.). MgD alone induced a 9-fold (vs. MgS, p <0.01) elevation in plasma SP; MgD+PR enhanced it further to 18-fold (p <0.001). Neutrophils from MgD+PR rats displayed a 3.9-fold higher (p <0.01) basal ·O2- generation, but those from MgD or PR alone were not activated. Plasma PGE2-metabolite levels rose 2.67- (p <0.01) and 1.56- (p <0.05) fold, respectively, in MgD+PR and MgD groups; the corresponding red blood cell glutathione levels were decreased 21 % (p <0.025) and 7 % (NS). MgD+PR significantly reduced neutrophil NEP activity by 48 % (p <0.02); PR or MgD alone only reduced this activity 26 % and 15 %, respectively. We conclude that NEP inhibition potentiates SP-mediated neutrophil ·O2- production and may promote other inflammatory activities during MgD. PMID:18607539

Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat.

PubMed

Mak, I T; Kramer, J H; Chmielinska, J J; Khalid, M H; Landgraf, K M; Weglicki, W B

2008-07-01

Neutral endopeptidase (NEP), which degrades substance P (SP), may regulate neutrophil activation during Mg-deficiency (MgD). Male Sprague-Dawley rats (180g) were fed MgD (approximately 50 mg Mg/kg) or Mg-sufficient (MgS, 608 mg Mg/kg) diets for 7 days +/- NEP inhibitor phosphoramidon (PR, 5 mg/kg/day, s.c.). MgD alone induced a 9-fold (vs. MgS, p <0.01) elevation in plasma SP; MgD+PR enhanced it further to 18-fold (p <0.001). Neutrophils from MgD+PR rats displayed a 3.9-fold higher (p <0.01) basal .O(2-) generation, but those from MgD or PR alone were not activated. Plasma PGE2-metabolite levels rose 2.67- (p <0.01) and 1.56- (p <0.05) fold, respectively, in MgD+PR and MgD groups; the corresponding red blood cell glutathione levels were decreased 21% (p <0.025) and 7% (NS). MgD+PR significantly reduced neutrophil NEP activity by 48% (p <0.02); PR or MgD alone only reduced this activity 26% and 15%, respectively. We conclude that NEP inhibition potentiates SP-mediated neutrophil .O(2-) production and may promote other inflammatory activities during MgD.

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against different Lyssavirus species

PubMed Central

Malerczyk, Claudius; Freuling, Conrad; Gniel, Dieter; Giesen, Alexandra; Selhorst, Thomas; Müller, Thomas

2014-01-01

Background: Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2. Material & Methods: Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV. Results: Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate). Conclusion: Cross-neutralizing activities partly correlate with the phylogenetic distance of the virus species. Cross-neutralizing activities against the species BBLV and DUVV of phylogroup 1 were demonstrated, in line with previous results of cross-neutralizing activities against ABLV and EBLV-1 and -2. Potential partial cross-neutralizing activities against more distant lyssavirus species like selected MOKV strains need further research. PMID:25483634

Can we reduce the effort of maintaining a neutral sitting posture? A pilot study.

PubMed

O'Sullivan, Kieran; McCarthy, Raymond; White, Alison; O'Sullivan, Leonard; Dankaerts, Wim

2012-12-01

Neutral sitting postures encouraging lumbar lordosis have been recommended in the management of sitting-related low back pain (LBP). However, prolonged lordotic sitting postures can be associated with increased fatigue and discomfort. This pilot study investigated whether changing the type of chair used in sitting can reduce the effort of maintaining a neutral sitting posture. The muscle activation of six trunk muscles was recorded using surface electromyography in 12 painfree participants. Participants were facilitated into a neutral sitting posture for 1 min on both a standard backless office chair and a dynamic, forward-inclined chair (Back App). Lumbar multifidus activity was significantly lower on the Back App chair (p=0.013). None of the other five trunk muscles measured demonstrated a significant difference in activity between the chairs. There was no significant difference (p=0.108) in the perceived effort of maintaining the neutral sitting posture on the two chairs. This study suggests that the lumbar multifidus activation required to maintain a neutral sitting posture can be reduced by considering the type of chair used. The mechanism through which the Back App chair reduces lumbar multifidus activation is unclear, but the greatest difference between chairs is the degree of hip flexion. The ability to maintain a neutral lumbar posture with less lumbar multifidus activation is potentially advantageous during prolonged sitting. Further investigations of the effects of chair design on longer duration sitting, and among LBP subjects, are warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

Old and in pain: Enduring and situational effects of cultural aging stereotypes on older people's pain experiences.

PubMed

Bernardes, S F; Marques, S; Matos, M

2015-08-01

This study aimed to investigate the interplay between enduring and situational aging stereotype (AS) effects in older adults' self-reports of clinical and experimentally induced pain. We expected that, as compared with the situational activation of positive AS or a neutral condition, the activation of negative AS would lead to more severe self-reports of clinical pain (H1, hypothesis 1), higher cold pressor task (CPT) pain threshold (H2) and lower CPT pain tolerance (H3), especially among older adults who more strongly endorsed AS. This was a prospective study across two moments in time. At time 1 (T1), 52 older adults (Mage  = 74.7; 51.9% women) filled out measures of cultural AS endorsement, clinical pain severity and interference. Three months afterwards (T2), some of these participants collaborated in an experimental study on the effects of AS activation on reported clinical pain (n = 40) and experimentally induced (using CPT) pain threshold and tolerance (n = 35). Our results supported H2, i.e., as compared with the activation of positive AS or a neutral condition, when negative AS were activated older adults showed higher CPT pain thresholds, but this effect was more salient among those who more strongly endorsed AS at T1. This study stresses the influence of cultural AS in older adults' pain experiences showing that the situational activation of negative AS greatly increases experimentally induced pain thresholds of elders who more strongly endorse those stereotypes. It also highlights the relevance of interventions at the level of the physical and/or social environments surrounding elders in pain. © 2014 European Pain Federation - EFIC®

Amygdala excitability to subliminally presented emotional faces distinguishes unipolar and bipolar depression: an fMRI and pattern classification study.

PubMed

Grotegerd, Dominik; Stuhrmann, Anja; Kugel, Harald; Schmidt, Simone; Redlich, Ronny; Zwanzger, Peter; Rauch, Astrid Veronika; Heindel, Walter; Zwitserlood, Pienie; Arolt, Volker; Suslow, Thomas; Dannlowski, Udo

2014-07-01

Bipolar disorder and Major depressive disorder are difficult to differentiate during depressive episodes, motivating research for differentiating neurobiological markers. Dysfunctional amygdala responsiveness during emotion processing has been implicated in both disorders, but the important rapid and automatic stages of emotion processing in the amygdala have so far never been investigated in bipolar patients. fMRI data of 22 bipolar depressed patients (BD), 22 matched unipolar depressed patients (MDD), and 22 healthy controls (HC) were obtained during processing of subliminal sad, happy and neutral faces. Amygdala responsiveness was investigated using standard univariate analyses as well as pattern-recognition techniques to differentiate the two clinical groups. Furthermore, medication effects on amygdala responsiveness were explored. All subjects were unaware of the emotional faces. Univariate analysis revealed a significant group × emotion interaction within the left amygdala. Amygdala responsiveness to sad>neutral faces was increased in MDD relative to BD. In contrast, responsiveness to happy>neutral faces showed the opposite pattern, with higher amygdala activity in BD than in MDD. Most of the activation patterns in both clinical groups differed significantly from activation patterns of HC--and therefore represent abnormalities. Furthermore, pattern classification on amygdala activation to sad>happy faces yielded almost 80% accuracy differentiating MDD and BD patients. Medication had no significant effect on these findings. Distinct amygdala excitability during automatic stages of the processing of emotional faces may reflect differential pathophysiological processes in BD versus MDD depression, potentially representing diagnosis-specific neural markers mostly unaffected by current psychotropic medication. Copyright © 2013 Wiley Periodicals, Inc.

Contribution of Field Strength Gradients to the Net Vertical Current of Active Regions

NASA Astrophysics Data System (ADS)

Vemareddy, P.

2017-12-01

We examined the contribution of field strength gradients for the degree of net vertical current (NVC) neutralization in active regions (ARs). We used photospheric vector magnetic field observations of AR 11158 obtained by Helioseismic and Magnetic Imager on board SDO and Hinode. The vertical component of the electric current is decomposed into twist and shear terms. The NVC exhibits systematic evolution owing to the presence of the sheared polarity inversion line between rotating and shearing magnetic regions. We found that the sign of shear current distribution is opposite in dominant pixels (60%–65%) to that of twist current distribution, and its time profile bears no systematic trend. This result indicates that the gradient of magnetic field strength contributes to an opposite signed, though smaller in magnitude, current to that contributed by the magnetic field direction in the vertical component of the current. Consequently, the net value of the shear current is negative in both polarity regions, which when added to the net twist current reduces the direct current value in the north (B z > 0) polarity, resulting in a higher degree of NVC neutralization. We conjecture that the observed opposite signs of shear and twist currents are an indication, according to Parker, that the direct volume currents of flux tubes are canceled by their return currents, which are contributed by field strength gradients. Furthermore, with the increase of spatial resolution, we found higher values of twist, shear current distributions. However, the resolution effect is more useful in resolving the field strength gradients, and therefore suggests more contribution from shear current for the degree of NVC neutralization.

Prime-Boost Immunization of Rabbits with HIV-1 gp120 Elicits Potent Neutralization Activity against a Primary Viral Isolate

PubMed Central

Narayan, Kristin M.; Agrawal, Nitish; Du, Sean X.; Muranaka, Janelle E.; Bauer, Katherine; Leaman, Daniel P.; Phung, Pham; Limoli, Kay; Chen, Helen; Boenig, Rebecca I.; Wrin, Terri; Zwick, Michael B.; Whalen, Robert G.

2013-01-01

Development of a vaccine for HIV-1 requires a detailed understanding of the neutralizing antibody responses that can be experimentally elicited to difficult-to-neutralize primary isolates. Rabbits were immunized with the gp120 subunit of HIV-1 JR-CSF envelope (Env) using a DNA-prime protein-boost regimen. We analyzed five sera that showed potent autologous neutralizing activity (IC50s at ∼103 to 104 serum dilution) against pseudoviruses containing Env from the primary isolate JR-CSF but not from the related isolate JR-FL. Pseudoviruses were created by exchanging each variable and constant domain of JR-CSF gp120 with that of JR-FL or with mutations in putative N-glycosylation sites. The sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions located on the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera are generally distinct from those of several well characterized mAbs (targeting conserved sites on Env) or other type-specific responses (targeting V1, V2, or V3 variable regions). The activity of one serum requires specific glycans that are also important for 2G12 neutralization and this serum blocked the binding of 2G12 to gp120. Our findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth. PMID:23326351

Neutralization efficiency of alcohol based products used for rapid hand disinfection

PubMed

Chojecka, Agnieszka; Tarka, Patryk; Kierzkowska, Anna; Nitsch-Osuch, Aneta; Kanecki, Krzysztof

Alcohols are the most commonly used active substances in preparations for quick hand disinfection. They should be bactericidal in very short contact time. PN-EN 13727 + A2: 2015-12 standard, for testing hygienic and surgical handrub disinfection preparations, provides mandatory test conditions of disinfectants in contact times with the range of 30 s to 60 s (hygienic handrub disinfection) and 60 s to 5 min (surgical handrub disinfection). A short contact times for hand hygiene products require a short time of neutralization process. For contact times less than or equal to 10 minutes, the estimated neutralization time is 10 s ± 1 s. Neutralization is a process that abolishes the action of disinfectants. Correct application of this process allows for proper use of disinfectants in practice and its biocidal effect. Objectives. Verification of the effectiveness of 10-second neutralization time of alcohol based preparations for hygienic handrub disinfection Neutralization of two products with different ethanol content (89% and 70%) for hygienic handrub disinfection according to PN-EN 13727 + A2: 2015-12 was investigated. The effectiveness of the neutralizer was assessed by determining toxicity of neutralizer, activity of residual effects of the tested products and their derivatives produced during neutralization (10 s) for test organisms (Staphylococcus aureus ATCC 6538; Pseudomonas aeruginosa ATCC 15442; Enterococcus hirae ATCC 10541; Escherichia coli K12 NCTC 10538) The 10-second neutralization time was sufficient to eliminate the residual activity of products for hygienic handrub disinfection with differentiated ethanol concentration. The neutralizer used did not show toxicity to bacteria and did not produce toxic products with tested preparations after neutralization Conclusions. The use of 10-second neutralization time allows in a precise way designate the contact times for hygienic handrub disinfection products

Synthesis, spectroscopic, and photophysical characterization and photosensitizing activity toward prokaryotic and eukaryotic cells of porphyrin-magainin and -buforin conjugates.

PubMed

Dosselli, Ryan; Ruiz-González, Rubén; Moret, Francesca; Agnolon, Valentina; Compagnin, Chiara; Mognato, Maddalena; Sella, Valentina; Agut, Montserrat; Nonell, Santi; Gobbo, Marina; Reddi, Elena

2014-02-27

Cationic antimicrobial peptides (CAMPs) and photodynamic therapy (PDT) are attractive tools to combat infectious diseases and to stem further development of antibiotic resistance. In an attempt to increase the efficiency of bacteria inactivation, we conjugated a PDT photosensitizer, cationic or neutral porphyrin, to a CAMP, buforin or magainin. The neutral and hydrophobic porphyrin, which is not photoactive per se against Gram-negative bacteria, efficiently photoinactivated Escherichia coli after conjugation to either buforin or magainin. Conjugation to magainin resulted in the considerable strengthening of the cationic and hydrophilic porphyrin's interaction with the bacterial cells, as shown by the higher bacteria photoinactivation activity retained after washing the bacterial suspension. The porphyrin-peptide conjugates also exhibited strong interaction capability as well as photoactivity toward eukaryotic cells, namely, human fibroblasts. These findings suggest that these CAMPs have the potential to carry drugs and other types of cargo inside mammalian cells similar to cell-penetrating peptides.

Listening to music reduces eye movements.

PubMed

Schäfer, Thomas; Fachner, Jörg

2015-02-01

Listening to music can change the way that people visually experience the environment, probably as a result of an inwardly directed shift of attention. We investigated whether this attentional shift can be demonstrated by reduced eye movement activity, and if so, whether that reduction depends on absorption. Participants listened to their preferred music, to unknown neutral music, or to no music while viewing a visual stimulus (a picture or a film clip). Preference and absorption were significantly higher for the preferred music than for the unknown music. Participants exhibited longer fixations, fewer saccades, and more blinks when they listened to music than when they sat in silence. However, no differences emerged between the preferred music condition and the neutral music condition. Thus, music significantly reduces eye movement activity, but an attentional shift from the outer to the inner world (i.e., to the emotions and memories evoked by the music) emerged as only one potential explanation. Other explanations, such as a shift of attention from visual to auditory input, are discussed.

Fiction feelings in Harry Potter: haemodynamic response in the mid-cingulate cortex correlates with immersive reading experience.

PubMed

Hsu, Chun-Ting; Conrad, Markus; Jacobs, Arthur M

2014-12-03

Immersion in reading, described as a feeling of 'getting lost in a book', is a ubiquitous phenomenon widely appreciated by readers. However, it has been largely ignored in cognitive neuroscience. According to the fiction feeling hypothesis, narratives with emotional contents invite readers more to be empathic with the protagonists and thus engage the affective empathy network of the brain, the anterior insula and mid-cingulate cortex, than do stories with neutral contents. To test the hypothesis, we presented participants with text passages from the Harry Potter series in a functional MRI experiment and collected post-hoc immersion ratings, comparing the neural correlates of passage mean immersion ratings when reading fear-inducing versus neutral contents. Results for the conjunction contrast of baseline brain activity of reading irrespective of emotional content against baseline were in line with previous studies on text comprehension. In line with the fiction feeling hypothesis, immersion ratings were significantly higher for fear-inducing than for neutral passages, and activity in the mid-cingulate cortex correlated more strongly with immersion ratings of fear-inducing than of neutral passages. Descriptions of protagonists' pain or personal distress featured in the fear-inducing passages apparently caused increasing involvement of the core structure of pain and affective empathy the more readers immersed in the text. The predominant locus of effects in the mid-cingulate cortex seems to reflect that the immersive experience was particularly facilitated by the motor component of affective empathy for our stimuli from the Harry Potter series featuring particularly vivid descriptions of the behavioural aspects of emotion.

Single-Chain Fv-Based Anti-HIV Proteins: Potential and Limitations

PubMed Central

West, Anthony P.; Galimidi, Rachel P.; Gnanapragasam, Priyanthi N. P.

2012-01-01

The existence of very potent, broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) offers the potential for prophylaxis against HIV-1 infection by passive immunization or gene therapy. Both routes permit the delivery of modified forms of IgGs. Smaller reagents are favored when considering ease of tissue penetration and the limited capacities of gene therapy vectors. Immunoadhesin (single-chain fragment variable [scFv]-Fc) forms of IgGs are one class of relatively small reagent that has been explored for delivery by adeno-associated virus. Here we investigated the neutralization potencies of immunoadhesins compared to those of their parent IgGs. For the antibodies VRC01, PG9, and PG16, the immunoadhesins showed modestly reduced potencies, likely reflecting reduced affinities compared to those of the parent IgG, and the VRC01 immunoadhesin formed dimers and multimers with reduced neutralization potencies. Although scFv forms of neutralizing antibodies may exhibit affinity reductions, they provide a means of building reagents with multiple activities. Attachment of the VRC01 scFv to PG16 IgG yielded a bispecific reagent whose neutralization activity combined activities from both parent antibodies. Although the neutralization activity due to each component was partially reduced, the combined reagent is attractive since fewer strains escaped neutralization. PMID:22013046

Development of the self-learning machine for creating models of microprocessor of single-phase earth fault protection devices in networks with isolated neutral voltage above 1000 V

NASA Astrophysics Data System (ADS)

Utegulov, B. B.; Utegulov, A. B.; Meiramova, S.

2018-02-01

The paper proposes the development of a self-learning machine for creating models of microprocessor-based single-phase ground fault protection devices in networks with an isolated neutral voltage higher than 1000 V. Development of a self-learning machine for creating models of microprocessor-based single-phase earth fault protection devices in networks with an isolated neutral voltage higher than 1000 V. allows to effectively implement mathematical models of automatic change of protection settings. Single-phase earth fault protection devices.

The effect of orthographic and emotional neighbourhood in a colour categorization task.

PubMed

Camblats, Anna-Malika; Mathey, Stéphanie

2016-02-01

This study investigated whether and how the strength of reading interference in a colour categorization task can be influenced by lexical competition and the emotional characteristics of words not directly presented. Previous findings showed inhibitory effects of high-frequency orthographic and emotional neighbourhood in the lexical decision task. Here, we examined the effect of orthographic neighbour frequency according to the emotional valence of the higher-frequency neighbour in an emotional orthographic Stroop paradigm. Stimuli were coloured neutral words that had either (1) no orthographic neighbour (e.g. PISTIL [pistil]), (2) one neutral higher-frequency neighbour (e.g. tirade [tirade]/TIRAGE [draw]) or (3) one negative higher-frequency neighbour (e.g. idiome [idiom]/IDIOTE [idiotic]). The results showed that colour categorization times were longer for words with no orthographic neighbour than for words with one neutral neighbour of higher frequency and even longer when the higher-frequency neighbour was neutral rather than negative. Thus, it appears not only that the orthographic neighbourhood of the coloured stimulus words intervenes in a colour categorization task, but also that the emotional content of the neighbour contributes to response times. These findings are discussed in terms of lexical competition between the stimulus word and non-presented orthographic neighbours, which in turn would modify the strength of reading interference on colour categorization times.

High-field neutral beam injection for improving the Q of a gas dynamic trap-based fusion neutron source

NASA Astrophysics Data System (ADS)

Zeng, Qiusun; Chen, Dehong; Wang, Minghuang

2017-12-01

In order to improve the fusion energy gain (Q) of a gas dynamic trap (GDT)-based fusion neutron source, a method in which the neutral beam is obliquely injected at a higher magnetic field position rather than at the mid-plane of the GDT is proposed. This method is beneficial for confining a higher density of fast ions at the turning point in the zone with a higher magnetic field, as well as obtaining a higher mirror ratio by reducing the mid-plane field rather than increasing the mirror field. In this situation, collision scattering loss of fast ions with higher density will occur and change the confinement time, power balance and particle balance. Using an updated calculation model with high-field neutral beam injection for a GDT-based fusion neutron source conceptual design, we got four optimal design schemes for a GDT-based fusion neutron source in which Q was improved to two- to three-fold compared with a conventional design scheme and considering the limitation for avoiding plasma instabilities, especially the fire-hose instability. The distribution of fast ions could be optimized by building a proper magnetic field configuration with enough space for neutron shielding and by multi-beam neutral particle injection at different axial points.

Frontal activity during a verbal emotional working memory task in patients with Alzheimer's disease: A functional near-infrared spectroscopy study.

PubMed

Ateş, Fatma Ebru; Cangöz, Banu; Özel Kızıl, Erguvan Tuğba; Baskak, Bora; Baran, Zeynel; Özgüven, Halise Devrimci

2017-03-30

Emotional working memory (EWM) is suggested as a working memory (WM) type, distinguished to process emotional stimuli, and may or may not be spared in Alzheimer's disease (AD). The aim was to compare patients with AD and healthy older adults (HC) on verbal EWM performance and accompanying prefrontal cortex activity. Twenty AD patients along with 20 HC individuals are required to complete an emotional one-back task in three conditions (neutral, positive and negative word lists). Prefrontal oxyhemoglobin (oxyHb) concentrations were measured simultaneously by a 24- channel functional near infrared spectroscopy device. Correct response rates were similar in two groups in all conditions. Reaction times were comparable in the EWM positive condition but longer in the AD group in EWMneutral and negative conditions. In the HC group, emotional words had no significant effect on WM. On the other hand, positive compared to neutral words led to greater activation in the left ventral prefrontal cortex (VPFC) in AD group. When compared to HCs, activity in the VPFC was significantly higher in AD patients during the positive condition. Positive words facilitated WM performance in participants with AD. Activity in VPFC may be the functional correlate of this phenomenon. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Cognitive and physiological dissociations in response to emotional pictures in patients with anorexia.

PubMed

Nandrino, Jean-Louis; Berna, Guillaume; Hot, Pascal; Dodin, Vincent; Latrée, Julie; Decharles, Sandra; Sequeira, Henrique

2012-01-01

Recent studies suggest that patients with anorexia may express dissociated cognitive and physiological reactivities to emotional stimuli. The present research aimed to compare subjective and autonomic responses to pleasant, unpleasant and neutral scenes during a categorization task and an activation rating task in anorexic (AN), alexithymic (AL), depressed (DEP) and control participants (CONT). The participants first categorized pictures according to their emotional valence, followed by a rating of their activation level, concomitant with the recording of skin conductance responses (SCRs). Main findings showed that the AN patients presented major difficulty in categorizing pictures, particularly neutral ones. Contrary to the AL participants, this difficulty did not induce significant increases of SCR amplitude in the AN patients. In the second task, the AN patients rated the intensity of activation of unpleasant pictures higher than the AL participants and that of pleasant ones higher than the AL and CONT participants. In addition, no significant linear correlation was observed between the intensity of activation ratings and SCR amplitude in the AN, AL or DEP participants contrarily to what was observed for control participants. This lack of relation suggests a non-specific disconnection between physiological and cognitive self-reported responses to emotional stimuli. Our results highlight a specific form of emotional processing in the AN patients distinct from that observed in alexithymia or depression and characterized by a dissociation between cognitive and physiological responses. This kind of disconnection could be associated with emotional regulation processes and may benefit the AN patients by lowering the psychological stress response. Copyright © 2011 Elsevier Inc. All rights reserved.

Heliospheric Neutral Atom Spectra Between 0.01 and 6 keV fom IBEX

NASA Technical Reports Server (NTRS)

Fuselier, S. A.; Allegrini, F.; Bzowski, M.; Funsten, H. O.; Ghielmetti, A. G.; Gloeckler, G.; Heirtzler, D.; Janzen, P.; Kubiak, M.; Kucharek, H.;

A comparative study of capacitively coupled HBr/He, HBr/Ar plasmas for etching applications: Numerical investigation by fluid model

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

Gul, Banat, E-mail: banatgul@gmail.com; Research Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp; Aman-ur-Rehman, E-mail: amansadiq@gmail.com

Fluid model has been applied to perform a comparative study of hydrogen bromide (HBr)/He and HBr/Ar capacitively coupled plasma discharges that are being used for anisotropic etching process. This model has been used to identify the most dominant species in HBr based plasmas. Our simulation results show that the neutral species like H and Br, which are the key player in chemical etching, have bell shape distribution, while ions like HBr{sup +}, Br{sup +}, which play a dominant rule in the physical etching, have double humped distribution and show peaks near electrodes. It was found that the dilution of HBrmore » by Ar and/or He results in an increase in electron density and electron temperature, which results in more ionization and dissociation and hence higher densities of neutral and charged species can be achieved. The ratio of positive ion flux to the neutral flux increases with an increase in additive gas fraction. Compare to HBr/He plasma, the HBr/Ar plasma shows a maximum change in the ion density and flux and hence the etching rate can be considered in the ion-assisted and in the ion-flux etch regime in HBr/Ar discharge. The densities of electron and other dominant species in HBr/Ar plasma are higher than those of HBr/He plasma. The densities and fluxes of the active neutrals and positive ions for etching and subsequently chemical etching versus physical sputtering in HBr/Ar and HBr/He plasmas discharge can be controlled by tuning gas mixture ratio and the desire etching can be achieved.« less

THERMAL PRESSURES IN THE INTERSTELLAR MEDIUM OF THE MAGELLANIC CLOUDS

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

Welty, Daniel E.; York, Donald G.; Lauroesch, James T.

2016-04-20

We discuss the thermal pressures ( n {sub H} T ) in predominantly cold, neutral interstellar gas in the Magellanic Clouds, derived from analyses of the fine-structure excitation of neutral carbon, as seen in high-resolution Hubble Space Telescope /Space Telescope Imaging Spectrograph spectra of seven diverse sight lines in the LMC and SMC. Detailed fits to the line profiles of the absorption from C i, C i*, and C i** yield consistent column densities for the three to six C i multiplets detected in each sight line. In the LMC and SMC, N (C i{sub tot}) is consistent with Galacticmore » trends versus N (Na i) and N (CH), but is slightly lower versus N (K i) and N (H{sub 2}). As for N (Na i) and N (K i), N (C i{sub tot}) is generally significantly lower, for a given N (H{sub tot}), in the LMC and (especially) in the SMC, compared to the local Galactic relationship. For the LMC and SMC components with well-determined column densities for C i, C i*, and C i**, the derived thermal pressures are typically factors of a few higher than the values found for most cold, neutral clouds in the Galactic ISM. Such differences are consistent with the predictions of models for clouds in systems (like the LMC and SMC) that are characterized by lower metallicities, lower dust-to-gas ratios, and enhanced radiation fields—where higher pressures are required for stable cold, neutral clouds. The pressures may be further enhanced by energetic activity (e.g., due to stellar winds, star formation, and/or supernova remnants) in several of the regions probed by these sight lines. Comparisons are made with the C i observed in some quasar absorption-line systems.« less

Circulating CXCR5+CXCR3+PD-1lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth

PubMed Central

Martin-Gayo, Enrique; Cronin, Jacqueline; Hickman, Taylor; Ouyang, Zhengyu; Lindqvist, Madelene; Kolb, Kellie E.; Schulze zur Wiesch, Julian; Cubas, Rafael; Porichis, Filippos; Shalek, Alex K.; van Lunzen, Jan; Haddad, Elias K.; Walker, Bruce D.; Kaufmann, Daniel E.; Lichterfeld, Mathias; Yu, Xu G.

2017-01-01

HIV-1–specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5+CXCR3+PD-1lo CD4+ T cells. These CXCR3+PD-1lo Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3+PD-1lo Tfh-like cells contained higher proportions of stem cell–like memory T cells, and upon antigenic stimulation differentiated into PD-1hi Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5+CXCR3+PD-1lo cells represent a dendritic cell–primed precursor cell population for PD-1hi Tfh-like cells that may contribute to the generation of bnAbs in the absence of high-level viremia. PMID:28138558

Analysis of activation and shutdown contact dose rate for EAST neutral beam port

NASA Astrophysics Data System (ADS)

Chen, Yuqing; Wang, Ji; Zhong, Guoqiang; Li, Jun; Wang, Jinfang; Xie, Yahong; Wu, Bin; Hu, Chundong

2017-12-01

For the safe operation and maintenance of neutral beam injector (NBI), specific activity and shutdown contact dose rate of the sample material SS316 are estimated around the experimental advanced superconducting tokamak (EAST) neutral beam port. Firstly, the neutron emission intensity is calculated by TRANSP code while the neutral beam is co-injected to EAST. Secondly, the neutron activation and shutdown contact dose rates for the neutral beam sample materials SS316 are derived by the Monte Carlo code MCNP and the inventory code FISPACT-2007. The simulations indicate that the primary radioactive nuclides of SS316 are 58Co and 54Mn. The peak contact dose rate is 8.52 × 10-6 Sv/h after EAST shutdown one second. That is under the International Thermonuclear Experimental Reactor (ITER) design values 1 × 10-5 Sv/h.

A Correlation Between Length of Strong-Shear Neutral Lines and Total X-Ray Brightness in Active Regions

NASA Technical Reports Server (NTRS)

Falconer, D. A.

1997-01-01

From a sample of 7 MSFC vector magnetograms,of active regions and 17 Yohkoh SXT soft X-ray images of these active regions, we have found that the total x-ray brightness of an entire active region is correlated with the total length of neutral lines on which the magnetic field is both strong (less than 250 G) and strongly sheared (shear angle greater than 75 deg) in the same active region. This correlation, if not fortuitous, is additional evidence of the importance of strong-shear strong-field neutral lines to strong heating in active regions.

Memory retrieval of smoking-related images induce greater insula activation as revealed by an fMRI based delayed matching to sample task

PubMed Central

Janes, AC; Ross, RS; Farmer, S; Frederick, BB; Nickerson, L; Lukas, SE; Stern, CE

2013-01-01

Nicotine dependence is a chronic and difficult to treat disorder. While environmental stimuli associated with smoking precipitate craving and relapse, it is unknown whether smoking cues are cognitively processed differently than neutral stimuli. To evaluate working memory differences between smoking-related and neutral stimuli, we conducted a delay-match-to-sample (DMS) task concurrently with functional magnetic resonance imaging (fMRI) in nicotine dependent participants. The DMS task evaluates brain activation during the encoding, maintenance, and retrieval phases of working memory. Smoking images induced significantly more subjective craving, and greater midline cortical activation during encoding in comparison to neutral stimuli that were similar in content yet lacked a smoking component. The insula, which is involved in maintaining nicotine dependence, was active during the successful retrieval of previously viewed smoking vs. neutral images. In contrast, neutral images required more prefrontal cortex-mediated active maintenance during the maintenance period. These findings indicate that distinct brain regions are involved in the different phases of working memory for smoking-related vs. neutral images. Importantly the results implicate the insula in the retrieval of smoking-related stimuli, which is relevant given the insula’s emerging role in addiction. PMID:24261848

Memory retrieval of smoking-related images induce greater insula activation as revealed by an fMRI-based delayed matching to sample task.

PubMed

Janes, Amy C; Ross, Robert S; Farmer, Stacey; Frederick, Blaise B; Nickerson, Lisa D; Lukas, Scott E; Stern, Chantal E

2015-03-01

Nicotine dependence is a chronic and difficult to treat disorder. While environmental stimuli associated with smoking precipitate craving and relapse, it is unknown whether smoking cues are cognitively processed differently than neutral stimuli. To evaluate working memory differences between smoking-related and neutral stimuli, we conducted a delay-match-to-sample (DMS) task concurrently with functional magnetic resonance imaging (fMRI) in nicotine-dependent participants. The DMS task evaluates brain activation during the encoding, maintenance and retrieval phases of working memory. Smoking images induced significantly more subjective craving, and greater midline cortical activation during encoding in comparison to neutral stimuli that were similar in content yet lacked a smoking component. The insula, which is involved in maintaining nicotine dependence, was active during the successful retrieval of previously viewed smoking versus neutral images. In contrast, neutral images required more prefrontal cortex-mediated active maintenance during the maintenance period. These findings indicate that distinct brain regions are involved in the different phases of working memory for smoking-related versus neutral images. Importantly, the results implicate the insula in the retrieval of smoking-related stimuli, which is relevant given the insula's emerging role in addiction. © 2013 Society for the Study of Addiction.

Association with emotional information alters subsequent processing of neutral faces

PubMed Central

Riggs, Lily; Fujioka, Takako; Chan, Jessica; McQuiggan, Douglas A.; Anderson, Adam K.; Ryan, Jennifer D.

2014-01-01

The processing of emotional as compared to neutral information is associated with different patterns in eye movement and neural activity. However, the ‘emotionality’ of a stimulus can be conveyed not only by its physical properties, but also by the information that is presented with it. There is very limited work examining the how emotional information may influence the immediate perceptual processing of otherwise neutral information. We examined how presenting an emotion label for a neutral face may influence subsequent processing by using eye movement monitoring (EMM) and magnetoencephalography (MEG) simultaneously. Participants viewed a series of faces with neutral expressions. Each face was followed by a unique negative or neutral sentence to describe that person, and then the same face was presented in isolation again. Viewing of faces paired with a negative sentence was associated with increased early viewing of the eye region and increased neural activity between 600 and 1200 ms in emotion processing regions such as the cingulate, medial prefrontal cortex, and amygdala, as well as posterior regions such as the precuneus and occipital cortex. Viewing of faces paired with a neutral sentence was associated with increased activity in the parahippocampal gyrus during the same time window. By monitoring behavior and neural activity within the same paradigm, these findings demonstrate that emotional information alters subsequent visual scanning and the neural systems that are presumably invoked to maintain a representation of the neutral information along with its emotional details. PMID:25566024

Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency.

PubMed

Bournazos, Stylianos; Gazumyan, Anna; Seaman, Michael S; Nussenzweig, Michel C; Ravetch, Jeffrey V

2016-06-16

Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) suppress viremia in animal models of HIV-1 and humans. To achieve potent activity without the emergence of viral escape mutants, co-administration of different bNAbs is necessary to target distinct epitopes essential for viral fitness. Here, we report the development of bispecific anti-Env neutralizing antibodies (biNAbs) with potent activity. Synergistic activity of biNAbs was achieved by combining an engineered hinge domain of IgG3 to increase Fab domain flexibility necessary for hetero-bivalent binding to the Env trimer while retaining the functional properties of the IgG1-Fc. Compared to unmodified biNAbs, hinge domain variants exhibited substantially improved neutralization activity, with particular combinations showing evidence of synergistic neutralization potency in vitro and enhanced in vivo therapeutic activity in HIV-1-infected humanized mice. These findings suggest innovative strategies for generating biNAbs with enhanced neutralization breadth and potency, representing ideal candidate molecules for the control of HIV-1 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Context effects and false memory for alcohol words in adolescents.

PubMed

Zack, Martin; Sharpley, Justin; Dent, Clyde W; Stacy, Alan W

2009-03-01

This study assessed incidental recognition of Alcohol and Neutral words in adolescents who encoded the words under distraction. Participants were 171 (87 male) 10th grade students, ages 14-16 (M=15.1) years. Testing was conducted by telephone: Participants listened to a list containing Alcohol and Neutral (Experimental--Group E, n=92) or only Neutral (Control--Group C, n=79) words, while counting backwards from 200 by two's. Recognition was tested immediately thereafter. Group C exhibited higher false recognition of Neutral than Alcohol items, whereas Group E displayed equivalent false rates for both word types. The reported number of alcohol TV ads seen in the past week predicted higher false recognition of Neutral words in Group C and of Alcohol words in Group E. False memory for Alcohol words in Group E was greater in males and high anxiety sensitive participants. These context-dependent biases may contribute to exaggerations in perceived drinking norms previously found to predict alcohol misuse in young drinkers.

Personality trait inferences of Turkish immigrant and neutral targets: an experimental study.

PubMed

Sandal, Gro M; Bye, Hege H; Pallesen, Ståle

2012-12-01

The study investigated whether personality traits attributed to immigrant targets differ from personality inferences made for a neutral target, and whether trait attributions differ for assimilated and integrated immigrant targets. Participants (n = 340) were randomized to one of three conditions in which they read the same story about a person, but where the person was described as either: (a) an assimilated Turkish immigrant; (b) an integrated Turkish immigrant; or (c) neutral (no nationality or religious practice indicated). Subsequently, they rated the personality of the described person on the NEO-Five Factor Inventory (observer rating version) and completed the Balanced Inventory of Desirable Responding (Impression Management scale) with reference to themselves. Both immigrant targets were rated as significantly higher on extraversion and lower on neuroticism than the neutral target. The integrated target was rated as more open than the neutral target, and as higher than the assimilated target on neuroticism when controlling for impression management. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

[The effect of aluminum adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine].

PubMed

Wang, Fang; Zhang, Ming; Xie, Bing-Feng; Cao, Han; Tong, Shao-Yong; Wang, Jun-Rong; Yu, Xiao-Ping; Tang, Yang; Yang, Jing-Ran; Sun, Ming-Bo

2013-04-01

To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine. Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay. The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant. Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.

Neural representation of anxiety and personality during exposure to anxiety-provoking and neutral scenes from scary movies.

PubMed

Straube, Thomas; Preissler, Sandra; Lipka, Judith; Hewig, Johannes; Mentzel, Hans-Joachim; Miltner, Wolfgang H R

2010-01-01

Some people search for intense sensations such as being scared by frightening movies while others do not. The brain mechanisms underlying such inter-individual differences are not clear. Testing theoretical models, we investigated neural correlates of anxiety and the personality trait sensation seeking in 40 subjects who watched threatening and neutral scenes from scary movies during functional magnetic resonance imaging. Threat versus neutral scenes induced increased activation in anterior cingulate cortex, insula, thalamus, and visual areas. Movie-induced anxiety correlated positively with activation in dorsomedial prefrontal cortex, indicating a role for this area in the subjective experience of being scared. Sensation seeking-scores correlated positively with brain activation to threat versus neutral scenes in visual areas and in thalamus and anterior insula, i.e. regions involved in the induction and representation of arousal states. For the insula and thalamus, these outcomes were partly due to an inverse relation between sensation seeking scores and brain activation during neutral film clips. These results support models predicting cerebral hypoactivation in high sensation seekers during neutral stimulation, which may be compensated by more intense sensations such as watching scary movies. 2009 Wiley-Liss, Inc.

Increased Antibody Affinity Confers Broad In Vitro Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus

PubMed Central

Rani, Mridula; Bolles, Meagan; Donaldson, Eric F.; Van Blarcom, Thomas; Baric, Ralph; Iverson, Brent

2012-01-01

Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (KD) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection. PMID:22696652

Different Timing Features in Brain Processing of Core and Moral Disgust Pictures: An Event-Related Potentials Study

PubMed Central

Zhang, Youxue; Lou, Liandi; Ding, Daoqun

2015-01-01

Disgust, an emotion motivating withdrawal from offensive stimuli, protects us from the risk of biological pathogens and sociomoral violations. Homogeneity of its two types, namely, core and moral disgust has been under intensive debate. To examine the dynamic relationship between them, we recorded event-related potentials (ERPs) for core disgust, moral disgust and neutral pictures while participants performed a modified oddball task. ERP analysis revealed that N1 and P2 amplitudes were largest for the core disgust pictures, indicating automatic processing of the core disgust-evoking pictures. N2 amplitudes were higher for pictures evoking moral disgust relative to core disgust and neutral pictures, reflecting a violation of social norms. The core disgust pictures elicited larger P3 and late positive potential (LPP) amplitudes in comparison with the moral disgust pictures which, in turn, elicited larger P3 and LPP amplitudes when compared to the neutral pictures. Taken together, these findings indicated that core and moral disgust pictures elicited different neural activities at various stages of information processing, which provided supporting evidence for the heterogeneity of disgust. PMID:26011635

Different timing features in brain processing of core and moral disgust pictures: an event-related potentials study.

PubMed

Zhang, Xiangyi; Guo, Qi; Zhang, Youxue; Lou, Liandi; Ding, Daoqun

2015-01-01

Disgust, an emotion motivating withdrawal from offensive stimuli, protects us from the risk of biological pathogens and sociomoral violations. Homogeneity of its two types, namely, core and moral disgust has been under intensive debate. To examine the dynamic relationship between them, we recorded event-related potentials (ERPs) for core disgust, moral disgust and neutral pictures while participants performed a modified oddball task. ERP analysis revealed that N1 and P2 amplitudes were largest for the core disgust pictures, indicating automatic processing of the core disgust-evoking pictures. N2 amplitudes were higher for pictures evoking moral disgust relative to core disgust and neutral pictures, reflecting a violation of social norms. The core disgust pictures elicited larger P3 and late positive potential (LPP) amplitudes in comparison with the moral disgust pictures which, in turn, elicited larger P3 and LPP amplitudes when compared to the neutral pictures. Taken together, these findings indicated that core and moral disgust pictures elicited different neural activities at various stages of information processing, which provided supporting evidence for the heterogeneity of disgust.

Spontaneous modification of carbon surface with neutral red from its diazonium salts for bioelectrochemical systems.

PubMed

Guo, Kun; Chen, Xin; Freguia, Stefano; Donose, Bogdan C

2013-09-15

This study introduces a novel and simple method to covalently graft neutral red (NR) onto carbon surfaces based on spontaneous reduction of in situ generated NR diazonium salts. Immobilization of neutral red on carbon surface was achieved by immersing carbon electrodes in NR-NaNO2-HCl solution. The functionalized electrodes were characterized by cyclic voltammetry (CV), atomic force microscope (AFM), and X-ray photoelectron spectroscopy (XPS). Results demonstrated that NR attached in this way retains high electrochemical activity and proved that NR was covalently bound to the carbon surface via the pathway of reduction of aryl diazonium salts. The NR-modified electrodes showed a good stability when stored in PBS solution in the dark. The current output of an acetate-oxidising microbial bioanode made of NR-modified graphite felts were 3.63±0.36 times higher than the unmodified electrodes, which indicates that covalently bound NR can act as electron transfer mediator to facilitate electron transfer from bacteria to electrodes. Copyright © 2013 Elsevier B.V. All rights reserved.

Antibodies against viruses: passive and active immunization

PubMed Central

Law, Mansun; Hangartner, Lars

2008-01-01

Summary of recent advances Antibodies, through passive or active immunization, play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies in protection against most viruses, the relative contribution of Fc-dependent and complement-dependent antiviral activities of antibodies was found to vary between different viruses in recent studies. The multiple hit model explains how antibodies neutralize viruses and recent data on the stoichiometry of antibody neutralization suggest that the organization of viral surface proteins on viruses, in addition to virus size, influences the level of antibody occupancy required for neutralization. These new findings will improve our strategies in therapeutic antibody engineering and rational vaccine design. PMID:18577455

Two Major Medicinal Honeys Have Different Mechanisms of Bactericidal Activity

PubMed Central

Kwakman, Paulus H. S.; te Velde, Anje A.; de Boer, Leonie; Vandenbroucke-Grauls, Christina M. J. E.; Zaat, Sebastian A. J.

2011-01-01

Honey is increasingly valued for its antibacterial activity, but knowledge regarding the mechanism of action is still incomplete. We assessed the bactericidal activity and mechanism of action of Revamil® source (RS) honey and manuka honey, the sources of two major medical-grade honeys. RS honey killed Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa within 2 hours, whereas manuka honey had such rapid activity only against B. subtilis. After 24 hours of incubation, both honeys killed all tested bacteria, including methicillin-resistant Staphylococcus aureus, but manuka honey retained activity up to higher dilutions than RS honey. Bee defensin-1 and H2O2 were the major factors involved in rapid bactericidal activity of RS honey. These factors were absent in manuka honey, but this honey contained 44-fold higher concentrations of methylglyoxal than RS honey. Methylglyoxal was a major bactericidal factor in manuka honey, but after neutralization of this compound manuka honey retained bactericidal activity due to several unknown factors. RS and manuka honey have highly distinct compositions of bactericidal factors, resulting in large differences in bactericidal activity. PMID:21394213

Neutrality as Obstructionist in Academic Activism: Calling Bullshit

ERIC Educational Resources Information Center

Rose, Barbara J.

2018-01-01

In this essay, the author uses experiences as a teacher educator and learning from a historically significant activism movement to (a) compare values in activism-centered and education-centered organizations, (b) posit ways that the concept of neutrality weakens academic activism, and (c) call for teacher education curricula and practices that…

Bacteriocin-like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains.

PubMed

Boyanova, L; Gergova, G; Markovska, R; Yordanov, D; Mitov, I

2017-12-01

The aim of the study was to detect anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains by four cell-free supernatant (CFS) types. Activity of non-neutralized and non-heat-treated (CFSs1), non-neutralized and heat-treated (CFSs2), pH neutralized, catalase-treated and non-heat-treated (CFSs3), or neutralized, catalase- and heat-treated (CFSs4) CFSs against 18 H. pylori strains (11 of which with antibiotic resistance) was evaluated. All GLB strains produced bacteriocin-like inhibitory substances (BLISs), the neutralized CFSs of two GLB strains inhibited >81% of test strains and those of four GLB strains were active against >71% of antibiotic resistant strains. Two H. pylori strains were BLIS resistant. The heating did not reduce the CFS activity. Briefly, all GLB strains evaluated produced heat-stable BLISs, although GLB and H. pylori strain susceptibility patterns exhibited differences. Bacteriocin-like inhibitory substance activity can be an advantage for the probiotic choice for H. pylori infection control. In this study, anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains was evaluated by four cell-free supernatant (CFS) types. The GLB strains produced heat-stable bacteriocin-like inhibitory substances (BLISs) with a strong anti-H. pylori activity and some neutralized, catalase- and heat-treated CFSs inhibited >83% of the test strains. Bacteriocin-like inhibitory substance production of GLB strains can render them valuable probiotics in the control of H. pylori infection. © 2017 The Society for Applied Microbiology.

Immunogenicity of ORFV-based vectors expressing the rabies virus glycoprotein in livestock species.

PubMed

Martins, Mathias; Joshi, Lok R; Rodrigues, Fernando S; Anziliero, Deniz; Frandoloso, Rafael; Kutish, Gerald F; Rock, Daniel L; Weiblen, Rudi; Flores, Eduardo F; Diel, Diego G

2017-11-01

The parapoxvirus Orf virus (ORFV) encodes several immunomodulatory proteins (IMPs) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. Here we describe the construction and characterization of two recombinant ORFV vectors expressing the rabies virus (RABV) glycoprotein (G). The RABV-G gene was inserted in the ORFV024 or ORFV121 gene loci, which encode for IMPs that are unique to parapoxviruses and inhibit activation of the NF-κB signaling pathway. The immunogenicity of the resultant recombinant viruses (ORFV ∆024 RABV-G or ORFV ∆121 RABV-G, respectively) was evaluated in pigs and cattle. Immunization of the target species with ORFV ∆024 RABV-G and ORFV ∆121 RABV-G elicited robust neutralizing antibody responses against RABV. Notably, neutralizing antibody titers induced in ORFV ∆121 RABV-G-immunized pigs and cattle were significantly higher than those detected in ORFV ∆024 RABV-G-immunized animals, indicating a higher immunogenicity of ORFV Δ121 -based vectors in these animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

[A comparative study on hydrolase activities in Acanthamoeba culbertsoni and A. royreba

PubMed

Kim, Yong Kyu; Kim, Tae Ue; Joung, In Sil; Im, Kyung Il

1988-06-01

Specific or non-specific cytolytic processes of free-living amoebae causing meningoencephalitis have been emphasized and the cytolytic ability related to hydrolases in Entamoeba sp. and Naegleria sp. has also been reported since the latter half of 1970's. However, no information on hydrolase activities in Acanthamoeba sp. is available. Hydrolases in Acanthamoeba culbertsoni, a pathogenic species of free-living amoebae, were assayed and compared with those in a non-pathogenic species, A. royreba. Pathogenicity of these two species was confirmed through experimental infection to BALB/c mice. Hydrolase activities and cytotoxic effects between pathogenic and non-pathogenic species were compared in the trophozoites cultured in CGV media and in CHO cell line, respectively. The results are summarized as follows: The mice infected with A. culbertsoni were all dead 15 days after nasal inoculation, and the mean survival time was 8.5 days. Also the mice infected with this pathogenic species mani fested typical meningoencephalitis, whereas the mice infected with A. royreba did not. Hydrolases detected both in the cell extracts and culture media were acid phosphatase, beta-N-acetyl galactosaminidase, beta-N-acetyl glucosaminidase, alpha-mannosidase, neutral proteinase and acid proteinase, all of which were detected with remarkably higher rate in A.culbertsoni than in A. royreba. A. culbertsoni revealed strong cytotoxicity for the target CHO cells, whereas A. royreba did not show any specific cytotoxicity. About 80% of the target cells mixed with A. culbertsoni were dead 48 hours after cultivation, and more than 95% of the target cells were dead 72 hours after cultivation. Hydrolase activities in A. culbertsoni cultured with the target cell line were assayed according to the culture time. The activities of acid phosphatase, beta-N-acetyl glucosaminidase, beta-N-acetyl glucosaminidase, alpha-mannosidase and acid proteinase in this pathogenic amoeba were detected higher in amoeba extracts than in culture media up to 120 hours after cultivation, but after 120 hours of cultivation those activities were detected higher in culture media than in the amoeba lysates. Neutral proteinase activity in A. culbertsoni increased more in EBSS medium than in the lysate specimens although the activity in the extracts was generally steady according to the cultivation time. Summarizing the above results, it is concluded that there were differences in hydrolase activities between pathogenic A. culbertsoni and non-pathogenic A. royreba, and that some hydrolase activities were detected remarkably higher in A. culbertsoni which revealed strong cytotoxicity to the target CHO cell line.

Ion composition at comet 67P near perihelion: Rosetta/ROSINA measurements and modeling

NASA Astrophysics Data System (ADS)

Beth, Arnaud; Altwegg, Kathrin; Balsiger, Hans; Berthelier, Jean-Jacques; Calmonte, Ursina; Combi, Michael R.; De Keyser, Johan; Dhooghe, Frederik; Fiethe, Björn; Fuselier, Stephen; Galand, Marina; Gasc, Sébastien; Gombosi, T. I.; Hansen, Kenneth C.; Hässig, Myrtha; Héritier, Kévin; Kopp, Ernest; Le Roy, Léna; Peroy, Solène; Rubin, Martin; Sémon, Thierry; Tzou, Chia-Yu; Vigren, Erik

2016-10-01

On August 13th, 2015, comet 67P/Churyumov-Gerasimenko reached its perihelion at 1.24 AU, a milestone for its cometary activity observed by the European Space Agency's Rosetta spacecraft which arrived in August 2014. The Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA)/Comet Pressure Sensor (COPS) instrument onboard Rosetta measured local outgassing rates over 1028 molecules.s-1 in summer 2015. In the meantime, the ROSINA/Double Focusing Mass Spectrometer (DFMS) instrument measured the ion composition in the coma which was expected to be more diversified than during the early phase of the mission. Indeed, the increase in the cometary activity is expected to trigger new chemical pathways, yielding the formation of new cometary ions, other than the major water ions observed at larger heliocentric distances. Such new ion species can be produced from minor neutral species, such as those with proton affinity higher than that of water. This includes NH4+ whose detection has been recently reported (Beth et al., 2016).In this study, we propose to investigate other ion species during the perihelion period by:- analysing DFMS data to find any signature of substantial ion species,- modeling the ionosphere of 67P by driving the model with the neutral densities measured by DFMS and COPS to support or constrain the absence or the presence of these ion species,- discussing any discrepancy between observations and simulations.

Per- and poly-fluoroalkyl substances (PFASs) in the urban, industrial, and background atmosphere of Northeastern China coast around the Bohai Sea: Occurrence, partitioning, and seasonal variation

NASA Astrophysics Data System (ADS)

Yao, Yiming; Chang, Shuai; Zhao, Yangyang; Tang, Jianhui; Sun, Hongwen; Xie, Zhiyong

2017-10-01

Air samples were collected using high-volume samplers at two coastal towns on the Bohai Sea in China, 320 km apart, and at a background site (North Huangcheng Island) in the Bohai Sea, 50 km from the coast. A suite of neutral and ionic per- and poly-fluoroalkyl substances (PFASs) was investigated. Urban activity was related to high levels of neutral PFASs at Tianjin while perfluorooctanoic carboxylic acid (PFOA) was dominant in the atmosphere at Weifang, possibly due to industrial sources. Polyfluoroalkyl phosphoric acid diesters (diPAPs) occurred in the particle phase only, with a total concentration range of 0.02-6.72 pg m-3. The dominant homologue was 6:2 diPAP. PFASs profiles at NHI suggested direct atmospheric transport of neutral and ionic PFASs from source regions. Temperature-dependent partitioning of fluorotelomer alcohols (FTOHs) was observed in winter, when total concentrations and particle-phase fractions of FTOHs were significantly higher as compared to those in summer. Correlation analyses suggested more active gas-phase degradation of FTOHs in summer and likely heterogeneous degradation in both seasons. Overall, it is necessary to account for ionic PFASs in both gas and particle phases and particulate matter was important for atmospheric transport and for determining the fate of PFASs, especially in areas close to a source region.

Clinical and laboratory studies of the antacid and raft-forming properties of Rennie alginate suspension.

PubMed

Tytgat, G N; Simoneau, G

2006-03-15

Acid pockets at the gastro-oesophageal junction escape buffering from meals in the stomach. Combining high-dose antacid with alginate may therefore be of benefit in gastro-oesophageal reflux disease. To characterize the antacid and raft-forming properties of Rennie alginate suspension (containing high-dose antacid and alginate; Bayer Consumer Care, Bladel, the Netherlands). The in vitro acid-neutralizing capacity of Rennie algniate was compared with Gaviscon (Reckitt Benckiser, Slough, UK) by pH-recorded HCl titration. Alginate raft weight formed in vitro at different pH was used to evaluate the pH dependency of raft formation with each product. A double-blind, placebo-controlled, randomized crossover study also compared the antacid activity of Rennie alginate vs. placebo in vivo using continuous intragastric pH monitoring in 12 healthy fasting volunteers. Compared with Gaviscon, Rennie alginate had a higher acid-neutralizing capacity, greater maximum pH and longer duration of antacid activity in vitro. However, the two products produced comparable alginate rafts at each pH evaluated. In vivo, Rennie alginate provided rapid, effective and long-lasting acid neutralization, with an onset of action of <5 min, and duration of action of almost 90 min. The dual mode of action of Rennie alginate offers an effective treatment option for mild symptomatic gastro-oesophageal reflux disease particularly considering recent findings regarding 'acid pockets'.

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

PubMed Central

Dumas, Eric K.; Gross, Timothy; Larabee, Jason; Pate, Lance; Cuthbertson, Hannah; Charlton, Sue; Hallis, Bassam; Engler, Renata J. M.; Collins, Limone C.; Spooner, Christina E.; Chen, Hua; Ballard, Jimmy; James, Judith A.

2017-01-01

ABSTRACT Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of Bacillus anthracis that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with Bacillus anthracis spores or ET. This study compared humoral responses to ET in recipients of AVP (n = 33) versus anthrax vaccine adsorbed (AVA; n = 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 ± 58.6) of EF antibodies than AVA (4.2% and 7.8 ± 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines. PMID:28877928

Structural insights into the neutralization mechanism of monoclonal antibody 6C2 against ricin.

PubMed

Zhu, Yuwei; Dai, Jianxin; Zhang, Tiancheng; Li, Xu; Fang, Pengfei; Wang, Huajing; Jiang, Yongliang; Yu, Xiaojie; Xia, Tian; Niu, Liwen; Guo, Yajun; Teng, Maikun

2013-08-30

Ricin belongs to the type II ribosome-inactivating proteins that depurinate the universally conserved α-sarcin loop of rRNA. The RNA N-glycosidase activity of ricin also largely depends on the ribosomal proteins that play an important role during the process of rRNA depurination. Therefore, the study of the interaction between ricin and the ribosomal elements will be better to understand the catalysis mechanism of ricin. The antibody 6C2 is a mouse monoclonal antibody exhibiting unusually potent neutralizing ability against ricin, but the neutralization mechanism remains unknown. Here, we report the 2.8 Å crystal structure of 6C2 Fab in complex with the A-chain of ricin (RTA), which reveals an extensive antigen-antibody interface that contains both hydrogen bonds and van der Waals contacts. The complementarity-determining region loops H1, H2, H3, and L3 form a pocket to accommodate the epitope on the RTA (residues Asp(96)-Thr(116)). ELISA results show that Gln(98), Glu(99), Glu(102), and Thr(105) (RTA) are the key residues that play an important role in recognizing 6C2. With the perturbation of the 6C2 Fab-RTA interface, 6C2 loses its neutralization ability, measured based on the inhibition of protein synthesis in a cell-free system. Finally, we propose that the neutralization mechanism of 6C2 against ricin is that the binding of 6C2 hinders the interaction between RTA and the ribosome and the surface plasmon resonance and pulldown results confirm our hypothesis. In short, our data explain the neutralization mechanism of mAb 6C2 against ricin and provide a structural basis for the development of improved antibody drugs with better specificity and higher affinity.

Pigs naturally exposed to porcine circovirus type 2 (PCV2) generate antibody responses capable to neutralise PCV2 isolates of different genotypes and geographic origins.

PubMed

Kurtz, Sherry; Grau-Roma, Llorenç; Cortey, Martí; Fort, Maria; Rodríguez, Fernando; Sibila, Marina; Segalés, Joaquim

2014-03-06

Porcine circovirus type 2 (PCV2) is the essential infectious agent for PCV2-systemic disease (PCV2-SD, formerly known as postweaning multisystemic wasting syndrome) and other pathological conditions. Recent studies indicated antigenic variability amongst different PCV2 isolates and suggested that single amino acid changes within the capsid protein determine differences in the level of neutralization by specific monoclonal antibodies. The objective of the present study was to examine the cross-reactivity of PCV2 antibodies induced in the context of a natural infection against different PCV2 isolates belonging to genotypes PCV2a and PCV2b. Sera taken from several farms from animals of varying health status (PCV2-SD and age-matched healthy pigs and a set of slaughter-aged animals) were assayed for neutralizing activity against four PCV2 isolates from both predominant genotypes (PCV2a and PCV2b) and of differing geographic origins (Europe and North-America). Results showed that most of studied pigs (79 out of 82) contained neutralizing antibodies (NA) able to neutralize all four studied viral strains. Overall, pigs had significantly higher NA titres against PCV2a than against PCV2b (P < 0.001). Accordingly, studied serums were able to better neutralize Burgos390L4 and Stoon-1010 strains (PCV2a) than L-33-Sp-10-54 and MO/S-06 strains (PCV2b) (P < 0.001). No differences between capabilities of seroneutralization of viruses from different geographic origin were observed. Present data suggests that sequence differences between PCV2 isolates translate to functional antigenic differences in viral neutralization in vivo.

Expression of Human Immunodeficiency Virus Type 1 Neutralizing Antibody Fragments Using Human Vaginal Lactobacillus.

PubMed

Marcobal, Angela; Liu, Xiaowen; Zhang, Wenlei; Dimitrov, Antony S; Jia, Letong; Lee, Peter P; Fouts, Timothy R; Parks, Thomas P; Lagenaur, Laurel A

Eradication of human immunodeficiency virus type 1 (HIV-1) by vaccination with epitopes that produce broadly neutralizing antibodies is the ultimate goal for HIV prevention. However, generating appropriate immune responses has proven difficult. Expression of broadly neutralizing antibodies by vaginal colonizing lactobacilli provides an approach to passively target these antibodies to the mucosa. We tested the feasibility of expressing single-chain and single-domain antibodies (dAbs) in Lactobacillus to be used as a topical microbicide/live biotherapeutic. Lactobacilli provide an excellent platform to express anti-HIV proteins. Broadly neutralizing antibodies have been identified against epitopes on the HIV-1 envelope and have been made into active antibody fragments. We tested single-chain variable fragment m9 and dAb-m36 and its derivative m36.4 as prototype antibodies. We cloned and expressed the antibody fragments m9, m36, and m36.4 in Lactobacillus jensenii-1153 and tested the expression levels and functionality. We made a recombinant L. jensenii 1153-1128 that expresses dAb-m36.4. All antibody fragments m9, m36, and m36.4 were expressed by lactobacilli. However, we noted the smaller m36/m36.4 were expressed to higher levels, ≥3 μg/ml. All L. jensenii-expressed antibody fragments bound to gp120/CD4 complex; Lactobacillus-produced m36.4 inhibited HIV-1 BaL in a neutralization assay. Using a TZM-bl assay, we characterized the breadth of neutralization of the m36.4. Delivery of dAbs by Lactobacillus could provide passive transfer of these antibodies to the mucosa and longevity at the site of HIV-1 transmission.

Semiannual and solar activity variations of daytime plasma observed by DEMETER in the ionosphere-plasmasphere transition region

NASA Astrophysics Data System (ADS)

Li, L. Y.; Cao, J. B.; Yang, J. Y.; Berthelier, J. J.; Lebreton, J.-P.

2015-12-01

Using the plasma data of Detection of Electro-Magnetic Emissions Transmitted from Earthquake Regions (DEMETER) satellite and the NRLMSISE-00 atmospheric model, we examined the semiannual and solar activity variations of the daytime plasma and neutral composition densities in the ionosphere-plasmasphere transition region (~670-710 km). The results demonstrate that the semiannually latitudinal variation of the daytime oxygen ions (O+) is basically controlled by that of neutral atomic oxygen (O), whereas the latitude distributions of the helium and hydrogen ions (He+ and H+) do not fully depend on the neutral atomic helium (He) and hydrogen (H). The summer enhancement of the heavy oxygen ions is consistent with the neutral O enhancement in the summer hemisphere, and the oxygen ion density has significantly the summer-dense and winter-tenuous hemispheric asymmetry with respect to the dip equator. Although the winter enhancements of the lighter He+ and H+ ions are also associated with the neutral He and H enhancements in the winter hemisphere, the high-density light ions (He+ and H+) and electrons (e-) mainly appear at the low and middle magnetic latitudes (|λ| < 50°). The equatorial accumulations of the light plasma species indicate that the light charged particles (He+, H+, and e-) are easily transported by some equatorward forces (e.g., the magnetic mirror force and centrifugal force). The frequent Coulomb collisions between the charged particles probably lead to the particle trappings at different latitudes. Moreover, the neutral composition densities also influence their ion concentrations during different solar activities. From the low-F10.7 year (2007-2008) to the high-F10.7 year (2004-2005), the daytime oxygen ions and electrons increase with the increasing neutral atomic oxygen, whereas the daytime hydrogen ions tend to decrease with the decreasing neutral atomic hydrogen. The helium ion density has no obvious solar activity variation, suggesting that the generation (via the neutral He photoionization) and loss (via the charge exchange with neutral nitrogen N2 and/or the recombination with electrons) of the daytime He+ ions are comparable during different solar activities.

Biomechanical and ergonomic assessment of urban transit operators.

PubMed

Albert, Wayne J; Everson, Donald; Rae, Michelle; Callaghan, Jack P; Croll, Jim; Kuruganti, Usha

2014-01-01

The prevalence of neck and low back musculoskeletal injuries in transit operators has been shown to be high; with work absences exceeding double the National average. There is a lack of biomechanical data generated from field researches to inform on musculoskeletal risk associated with transportation and driving occupations. Instead there has been a reliance on simulated driving and questionnaire-based research. This study was designed to examine the musculoskeletal and biomechanical stresses experienced by urban bus drivers. The main objective was to obtain a baseline understanding of sitting posture, muscle activiation and subjective ratings of stress during regular driving tasks. Fifteen urban city bus drivers were recruited for this study. Bus drivers drove the same 65-minute bus route once, at the same time of day, in the same preselected bus. Wireless surface electromyography monitored muscular activity of the drivers' neck, upper trapezius, and erector spinae and video analysis and seat pressure mapping was used to monitor changes in driving posture. A health and lifestyle questionnaire was administered to record specific neck and back pain experienced by drivers as well as to provide lifestyle habits. Drivers were found to exhibit non-neutral postures for less than 30% of the time while conducting routine tasks of turning and stopping for passenger loading and unloading. The neck posture was the greatest concern in terms of non-neutral posture and this was supported by the higher muscle activation to the neck musculature. There was significant posture adjustment made during the one-hour driving period with the adjustments increasing with driving time. Activities associated with bus driving appear to require the use of non-neutral postures an increase in muscle activation. Significant postural adjustments were needed over the one-hour observation period suggesting that the musculoskeletal demands may increase over a regular 12-hour shift.

Functional condition of masseters muscles of patients with class ?? subdivision.

PubMed

Kuroyedova, Vera D; Makarova, Alexandra N; Chicor, Tatyana A

Main functional characteristics of masticator muscles in patients with class ?? malocclusions is activity dominance of m. temporalis in comparison with m. ?asseter. We have not found datum about functional status of the masticators in patients with class II subdivision. The purpose of our study was to investigate the functional characteristics of m. ?asseter, m. temporalis in adult patients with class II subdivision malocclusion. There have been carried out the surface electromyographic study of m. masseter, m. temporalis in 17 adult patients with class II subdivision. It was realized quantitative analysis of 271 electromyogram, it was determined the average bioelectric activity, index activity, symmetry and torsion index. It was observed predominance of the bioelectrical activity of m. temporales on m. masseter for all persons with class II subdivision. Bioelectrical activity for m. masseter was bigger on side of distal ratio and for m. temporales on side of neutral ratio. In class ?? subdivision right, the mandible was deviated to the left side and in class ?? subdivision left is deviated to the right side. Thus, rotational moment generated during compression of the jaws, causes deviation of the lower jaw to the side, with a neutral molar ratio. During voluntary chewing bioelectrical activity of m. masseter and m. temporalis was higher in the right side. In accordance with the functional condition of the masticatory muscles of class II subdivision is characterized with functional features of distal occlusion.

Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

PubMed

Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

2015-01-01

Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESN<3 yr, and HIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

Natural variability in bovine milk oligosaccharides from Danish Jersey and Holstein-Friesian breeds

PubMed Central

Sundekilde, Ulrik K; Barile, Daniela; Meyrand, Mickael; Poulsen, Nina A; Larsen, Lotte B; Lebrilla, Carlito B.; Bruce, German J.; Bertram, Hanne C

2012-01-01

Free oligosaccharides are key components of human milk and play multiple roles in the health of the neonate, by stimulating growth of selected beneficial bacteria in the gut, participating in development of the brain and exerting anti-pathogenic activity. However, the concentration of oligosaccharides is low in mature bovine milk, normally used for infant formula, compared with both human colostrum and mature human milk. Characterization of bovine milk oligosaccharides in different breeds is crucial for the identification of viable sources for oligosaccharide purification. An improved source of oligosaccharides can lead to infant formula with improved oligosaccharide functionality. In the present study we have analyzed milk oligosaccharides by high-performance liquid chromatography chip quadrupole time-of-flight mass spectrometry and performed a detailed data analysis using both univariate and multivariate methods. Both statistical tools revealed several differences in oligosaccharide profiles between milk samples from the two Danish breeds; Jersey and Holstein-Friesians. Jersey milk contained higher relative amounts of both sialylated and the more complex neutral fucosylated oligosaccharides, while the Holstein-Friesian milk had higher abundance of smaller and simpler neutral oligosaccharides. The statistical analyses revealed that Jersey milk contain significantly higher levels of fucosylated oligosaccharides than Holstein-Friesian milk. Jersey milk also possesses oligosaccharides with a higher degree of complexity and functional residues (fucose and sialic acid) suggesting it may therefore offer advantages in term of a wider array of bioactivities. PMID:22632419

The impact of antigenic drift of influenza A virus on human herd immunity: Sero-epidemiological study of H1N1 in healthy Thai population in 2009.

PubMed

Kanai, Yuta; Boonsathorn, Naphatsawan; Chittaganpitch, Malinee; Bai, Guirong; Li, Yonggang; Kase, Tetsuo; Takahashi, Kazuo; Okuno, Yoshinobu; Jampangern, Wipawee; Ikuta, Kazuyoshi; Sawanpanyalert, Pathom

2010-07-26

To examine the effect of the antigenic drift of H1N1 influenza viruses on herd immunity, neutralization antibodies from 744 sera from Thai healthy volunteers in 2008-2009, who had not been vaccinated for at least the last 5 years, were investigated by microneutralization (MN) and hemagglutination inhibition (HI) assays. Significantly higher MN titers were observed for the H1N1 Thai isolate in 2006 than in 2008. The results indicate that the antigenically drifted virus effectively escaped herd immunity. Since the low neutralization activity of herd immunity against drifted viruses is an important factor for viruses to spread efficiently, continuous sero-epidemiological study is required for public health. Copyright 2010 Elsevier Ltd. All rights reserved.

Influence of the social environment on children's school travel.

PubMed

McDonald, Noreen C; Deakin, Elizabeth; Aalborg, Annette E

2010-01-01

To analyze the association between parental perceptions of the social environment and walking and biking to school among 10-14-year-olds. Surveys were conducted with 432 parents of 10-14-year-olds in the San Francisco Bay Area during 2006 and 2007; the final sample size was 357. The social environment was measured with a 3-item scale assessing child-centered social control. Unadjusted and adjusted differences in rates of active travel to school were compared between families reporting high levels of social control in their neighborhood and those reporting low or neutral levels of social control. Adjusted differences were computed by matching respondents on child and household characteristics and distance to school. Of children whose parents reported high levels of social control, 37% walked or biked to school, compared with 24% of children whose parents reported low or neutral levels. The adjusted difference between the two groups was 10 percentage points (p=0.04). The association was strongest for girls and non-Hispanic whites. Higher levels of parent-perceived child-centered social control are associated with more walking and biking to school. Increasing physical activity through active travel to school may require intervention programs to address the social environment.

Collectors on illicit collecting: Higher loyalties and other techniques of neutralization in the unlawful collecting of rare and precious orchids and antiquities

PubMed Central

Mackenzie, Simon; Yates, Donna

2015-01-01

Trafficking natural objects and trafficking cultural objects have been treated separately both in regulatory policy and in criminological discussion. The former is generally taken to be ‘wildlife crime’ while the latter has come to be considered under the auspices of a debate on ‘illicit art and antiquities’. In this article we study the narrative discourse of high-end collectors of orchids and antiquities. The illicit parts of these global trades are subject to this analytical divide between wildlife trafficking and art trafficking, and this has resulted in quite different regulatory structures for each of these markets. However, the trafficking routines, the types and levels of harm involved, and the supply–demand dynamics in the trafficking of orchids and antiquities are actually quite similar, and in this study we find those structural similarities reflected in substantial common ground in the way collectors talk about their role in each market. Collectors of rare and precious orchids and antiquities valorize their participation in markets that are known to be in quite considerable degree illicit, appealing to ‘higher loyalties’ such as preservation, appreciation of aesthetic beauty and cultural edification. These higher loyalties, along with other techniques of neutralization, deplete the force of law as a guide to appropriate action. We propose that the appeal to higher loyalties is difficult to categorize as a technique of neutralization in this study as it appears to be a motivational explanation for the collectors involved. The other classic techniques of neutralization are deflective, guilt and critique reducing narrative mechanisms, while higher loyalties drives illicit behaviour in collecting markets for orchids and antiquities in ways that go significantly beyond the normal definition of neutralization. PMID:28066153

Collectors on illicit collecting: Higher loyalties and other techniques of neutralization in the unlawful collecting of rare and precious orchids and antiquities.

PubMed

Mackenzie, Simon; Yates, Donna

2016-08-01

Trafficking natural objects and trafficking cultural objects have been treated separately both in regulatory policy and in criminological discussion. The former is generally taken to be 'wildlife crime' while the latter has come to be considered under the auspices of a debate on 'illicit art and antiquities'. In this article we study the narrative discourse of high-end collectors of orchids and antiquities. The illicit parts of these global trades are subject to this analytical divide between wildlife trafficking and art trafficking, and this has resulted in quite different regulatory structures for each of these markets. However, the trafficking routines, the types and levels of harm involved, and the supply-demand dynamics in the trafficking of orchids and antiquities are actually quite similar, and in this study we find those structural similarities reflected in substantial common ground in the way collectors talk about their role in each market. Collectors of rare and precious orchids and antiquities valorize their participation in markets that are known to be in quite considerable degree illicit, appealing to 'higher loyalties' such as preservation, appreciation of aesthetic beauty and cultural edification. These higher loyalties, along with other techniques of neutralization, deplete the force of law as a guide to appropriate action. We propose that the appeal to higher loyalties is difficult to categorize as a technique of neutralization in this study as it appears to be a motivational explanation for the collectors involved. The other classic techniques of neutralization are deflective, guilt and critique reducing narrative mechanisms, while higher loyalties drives illicit behaviour in collecting markets for orchids and antiquities in ways that go significantly beyond the normal definition of neutralization.

A Fe(II)/citrate/UV/PMS process for carbamazepine degradation at a very low Fe(II)/PMS ratio and neutral pH: The mechanisms.

PubMed

Ling, Li; Zhang, Dapeng; Fan, Chihhao; Shang, Chii

2017-11-01

A novel Fe(II)/citrate/UV/PMS process for degrading a model micropollutant, carbamazepine (CBZ), at a low Fe(II)/PMS ratio and neutral pH has been proposed in this study, and the mechanisms of radical generation in the system was explored. With a UV dose of 302.4 mJ/cm 2 , an initial pH of 7, and CBZ, PMS, Fe(II) and citrate at initial concentrations of 10, 100, 12 and 26 μM, respectively, the CBZ degradation efficiency reached 71% in 20 min in the Fe(II)/citrate/UV/PMS process, which was 4.7 times higher than that in either the citrate/UV/PMS or Fe(II)/citrate/PMS process. The enhanced CBZ degradation in the Fe(II)/citrate/UV/PMS process was mainly attributed to the continuous activation of PMS by the UV-catalyzed regenerated Fe(II) from a Fe(III)-citrate complex, [Fe 3 O(cit) 3 H 3 ] 2- , which not only maintained Fe(III) soluble at neutral pH, but also increased 6.6 and 2.6 times of its molar absorbance and quantum yield as compared to those of ionic Fe(III), respectively. In the Fe(II)/citrate/UV/PMS process, the SO 4 •- produced from the fast reaction between PMS and the initially-added Fe(II) contributed 11% of CBZ degradation. The PMS activation by the UV radiation and regenerated Fe(II) contributed additional 14% and 46% of CBZ removal, respectively. The low iron and citrate doses and the fast radical generation at neutral pH make the Fe(II)/citrate/UV/PMS process suitable for degrading recalcitrant organic compounds in potable water. Copyright © 2017 Elsevier Ltd. All rights reserved.

Engineering of a recombinant trivalent single-chain variable fragment antibody directed against rabies virus glycoprotein G with improved neutralizing potency.

PubMed

Turki, Imène; Hammami, Akil; Kharmachi, Habib; Mousli, Mohamed

2014-02-01

Human and equine rabies immunoglobulins are currently available for passive immunization against rabies. However, these are hampered by the limited supply and some drawbacks. Advances in antibody engineering have led to overcome issues of clinical applications and to improve the protective efficacy. In the present study, we report the generation of a trivalent single-chain Fv (scFv50AD1-Fd), that recognizes the rabies virus glycoprotein, genetically fused to the trimerization domain of the bacteriophage T4 fibritin, termed 'foldon' (Fd). scFv50AD1-Fd was expressed as soluble recombinant protein in bacterial periplasmic space and purified through affinity chromatography. The molecular integrity and stability were analyzed by polyacrylamide gradient-gel electrophoresis, size-exclusion chromatography and incubation in human sera. The antigen-binding properties of the trimeric scFv were analyzed by direct and competitive-ELISA. Its apparent affinity constant was estimated at 1.4 ± 0.25 × 10(9)M(-1) and was 75-fold higher than its monovalent scFv (1.9 ± 0.68 × 10(7)M(-1)). The scFv50AD1-Fd neutralized rabies virus in a standard in vitro and in vivo neutralization assay. We showed a high neutralization activity up to 75-fold compared with monovalent format and the WHO standard serum. The gain in avidity resulting from multivalency along with an improved biological activity makes the trivalent scFv50AD1-Fd construct an important reagent for rabies protection. The antibody engineering approach presented here may serve as a strategy for designing a new generation of anti-rabies for passive immunotherapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Orientation Control in Thin Films of a High-χ Block Copolymer with a Surface Active Embedded Neutral Layer.

PubMed

Zhang, Jieqian; Clark, Michael B; Wu, Chunyi; Li, Mingqi; Trefonas, Peter; Hustad, Phillip D

2016-01-13

Directed self-assembly (DSA) of block copolymers (BCPs) is an attractive advanced patterning technology being considered for future integrated circuit manufacturing. By controlling interfacial interactions, self-assembled microdomains in thin films of polystyrene-block-poly(methyl methacrylate), PS-b-PMMA, can be oriented perpendicular to surfaces to form line/space or hole patterns. However, its relatively weak Flory interaction parameter, χ, limits its capability to pattern sub-10 nm features. Many BCPs with higher interaction parameters are capable of forming smaller features, but these "high-χ" BCPs typically have an imbalance in surface energy between the respective blocks that make it difficult to achieve the required perpendicular orientation. To address this challenge, we devised a polymeric surface active additive mixed into the BCP solution, referred to as an embedded neutral layer (ENL), which segregates to the top of the BCP film during casting and annealing and balances the surface tensions at the top of the thin film. The additive comprises a second BCP with a "neutral block" designed to provide matched surface tensions with the respective polymers of the main BCP and a "surface anchoring block" with very low surface energy that drives the material to the air interface during spin-casting and annealing. The surface anchoring block allows the film to be annealed above the glass transition temperature of the two materials without intermixing of the two components. DSA was also demonstrated with this embedded neutral top layer formulation on a chemical patterned template using a single step coat and simple thermal annealing. This ENL technology holds promise to enable the use of high-χ BCPs in advanced patterning applications.

Prefrontal control and predictors of cognitive behavioral therapy response in social anxiety disorder

PubMed Central

Fitzgerald, Daniel A.; Piejko, Katherine; Roberts, Julia; Kennedy, Amy E.; Phan, K. Luan

2016-01-01

Generalized social anxiety disorder (gSAD) is associated with aberrant anterior cingulate cortex (ACC) response to threat distractors. Perceptual load has been shown to modulate ACC activity such that under high load, when demands on processing capacity is restricted, individuals with gSAD exhibit compensatory activation to threat distractors yet under low load, there is evidence of reduced activation. It is not known if neural predictors of response to cognitive behavioral therapy (CBT), based on such emotional conflict resolution, interact with demands on controlled processes. Prior to CBT, 32 patients with gSAD completed an fMRI task involving a target letter in a string of identical targets (low perceptual load) or a target letter in a mixed letter string (high perceptual load) superimposed on fearful, angry and neutral face distractors. Whole-brain voxel-wise analyses revealed better CBT outcome was predicted by more frontopartial activity that included dorsal ACC (dACC) and insula to threat (vs neutral) distractors during high, but not low, perceptual load. Psychophysiological interaction analysis with dACC as the seed region revealed less connectivity with dorsolateral prefrontal cortex to threat distractors during high load. Results indicate patients with less regulatory capability when demands on higher-order control are great may benefit more from CBT. PMID:26634281

Sex-dependent dissociation between emotional appraisal and memory: a large-scale behavioral and fMRI study.

PubMed

Spalek, Klara; Fastenrath, Matthias; Ackermann, Sandra; Auschra, Bianca; Coynel, David; Frey, Julia; Gschwind, Leo; Hartmann, Francina; van der Maarel, Nadine; Papassotiropoulos, Andreas; de Quervain, Dominique; Milnik, Annette

2015-01-21

Extensive evidence indicates that women outperform men in episodic memory tasks. Furthermore, women are known to evaluate emotional stimuli as more arousing than men. Because emotional arousal typically increases episodic memory formation, the females' memory advantage might be more pronounced for emotionally arousing information than for neutral information. Here, we report behavioral data from 3398 subjects, who performed picture rating and memory tasks, and corresponding fMRI data from up to 696 subjects. We were interested in the interaction between sex and valence category on emotional appraisal, memory performances, and fMRI activity. The behavioral results showed that females evaluate in particular negative (p < 10(-16)) and positive (p = 2 × 10(-4)), but not neutral pictures, as emotionally more arousing (pinteraction < 10(-16)) than males. However, in the free recall females outperformed males not only in positive (p < 10(-16)) and negative (p < 5 × 10(-5)), but also in neutral picture recall (p < 3.4 × 10(-8)), with a particular advantage for positive pictures (pinteraction < 4.4 × 10(-10)). Importantly, females' memory advantage during free recall was absent in a recognition setting. We identified activation differences in fMRI, which corresponded to the females' stronger appraisal of especially negative pictures, but no activation differences that reflected the interaction effect in the free recall memory task. In conclusion, females' valence-category-specific memory advantage is only observed in a free recall, but not a recognition setting and does not depend on females' higher emotional appraisal. Copyright © 2015 the authors 0270-6474/15/350920-16$15.00/0.

Antibody expressing pea seeds as fodder for prevention of gastrointestinal parasitic infections in chickens.

PubMed

Zimmermann, Jana; Saalbach, Isolde; Jahn, Doreen; Giersberg, Martin; Haehnel, Sigrun; Wedel, Julia; Macek, Jeanette; Zoufal, Karen; Glünder, Gerhard; Falkenburg, Dieter; Kipriyanov, Sergey M

2009-09-11

Coccidiosis caused by protozoans of genus Eimeria is a chicken parasitic disease of great economical importance. Conventional disease control strategies depend on vaccination and prophylactic use of anticoccidial drugs. Alternative solution to prevent and treat coccidiosis could be provided by passive immunization using orally delivered neutralizing antibodies. We investigated the possibility to mitigate the parasitic infection by feeding poultry with antibody expressing transgenic crop seeds. Using the phage display antibody library, we generated a panel of anti-Eimeria scFv antibody fragments with high sporozoite-neutralizing activity. These antibodies were expressed either transiently in agrobacteria-infiltrated tobacco leaves or stably in seeds of transgenic pea plants. Comparison of the scFv antibodies purified either from tobacco leaves or from the pea seeds demonstrated no difference in their antigen-binding activity and molecular form compositions. Force-feeding experiments demonstrated that oral delivery of flour prepared from the transgenic pea seeds had higher parasite neutralizing activity in vivo than the purified antibody fragments isolated from tobacco. The pea seed content was found to protect antibodies against degradation by gastrointestinal proteases (>100-fold gain in stability). Ad libitum feeding of chickens demonstrated that the transgenic seeds were well consumed and not shunned. Furthermore, feeding poultry with shred prepared from the antibody expressing pea seeds led to significant mitigation of infection caused both by high and low challenge doses of Eimeria oocysts. The results suggest that our strategy offers a general approach to control parasitic infections in production animals using cost-effective antibody expression in crop seeds affordable for the animal health market.

Antibody expressing pea seeds as fodder for prevention of gastrointestinal parasitic infections in chickens

PubMed Central

Zimmermann, Jana; Saalbach, Isolde; Jahn, Doreen; Giersberg, Martin; Haehnel, Sigrun; Wedel, Julia; Macek, Jeanette; Zoufal, Karen; Glünder, Gerhard; Falkenburg, Dieter; Kipriyanov, Sergey M

2009-01-01

Background Coccidiosis caused by protozoans of genus Eimeria is a chicken parasitic disease of great economical importance. Conventional disease control strategies depend on vaccination and prophylactic use of anticoccidial drugs. Alternative solution to prevent and treat coccidiosis could be provided by passive immunization using orally delivered neutralizing antibodies. We investigated the possibility to mitigate the parasitic infection by feeding poultry with antibody expressing transgenic crop seeds. Results Using the phage display antibody library, we generated a panel of anti-Eimeria scFv antibody fragments with high sporozoite-neutralizing activity. These antibodies were expressed either transiently in agrobacteria-infiltrated tobacco leaves or stably in seeds of transgenic pea plants. Comparison of the scFv antibodies purified either from tobacco leaves or from the pea seeds demonstrated no difference in their antigen-binding activity and molecular form compositions. Force-feeding experiments demonstrated that oral delivery of flour prepared from the transgenic pea seeds had higher parasite neutralizing activity in vivo than the purified antibody fragments isolated from tobacco. The pea seed content was found to protect antibodies against degradation by gastrointestinal proteases (>100-fold gain in stability). Ad libitum feeding of chickens demonstrated that the transgenic seeds were well consumed and not shunned. Furthermore, feeding poultry with shred prepared from the antibody expressing pea seeds led to significant mitigation of infection caused both by high and low challenge doses of Eimeria oocysts. Conclusion The results suggest that our strategy offers a general approach to control parasitic infections in production animals using cost-effective antibody expression in crop seeds affordable for the animal health market. PMID:19747368

Structural features and complement-fixing activity of pectin from three Brassica oleracea varieties: white cabbage, kale, and red kale.

PubMed

Samuelsen, Anne Berit; Westereng, Bjørge; Yousif, Osman; Holtekjølen, Ann Katrin; Michaelsen, Terje E; Knutsen, Svein H

2007-02-01

Leaves of different cabbage species are used both as food and as wound healing remedies in traditional medicine. This supposed wound healing activity might be connected to presence of immunomodulating water soluble polysaccharides. To study this, three different cabbage varieties, white cabbage (W), kale (K), and red kale (RK), were pretreated with 80% ethanol and then extracted with water at 50 degrees C and 100 degrees C for isolation of polysaccharide-containing fractions. The fractions were analyzed for monosaccharide composition, glycosidic linkages, Mw distribution, protein content, and phenolic compounds and then tested for complement-fixing activity. All fractions contained pectin type polysaccharides with linkages corresponding to homogalacturonan and hairy regions. Those extracted at 50 degrees C contained higher amounts of neutral side chains and were more active in the complement-fixation test than those extracted at 100 degrees C. The fractions can be ranged by decreasing activity: K-50 > RK-50 > W-50 approximately = K-100 > RK100 approximately = W-100. Studies on structure-activity relationships (SAR) employing multivariate statistical analysis strongly suggest that the magnitude of the measured activity is influenced by the content of certain side chains in the polymers. High activity correlates to large neutral side chains with high amounts of (1-->6)- and (1-->3,6)-linked Gal and low amounts of (1-->4)-linked GalA but not on molecular weight distribution of the polymers.

Do Astronauts Havbe a Higher Rate of Orthopedic Shoulder Conditions Than a Cohort of Working Professionals

NASA Technical Reports Server (NTRS)

Laughlin, M. S.; Murray, J. D.; Young, M.; Wear, M. L.; Van Baalen, M.; Tarver, W. J.

2016-01-01

Occupational surveillance of astronaut shoulder injuries began with operational concerns at the Neutral Buoyancy Laboratory (NBL) during Extra Vehicular Activity (EVA) training. Orthopedic shoulder injury and surgery rates were calculated [1], but classifying the rates as normal, high or low was highly dependent on the comparison group. Thus, the purpose of this study was to identify a population of working professionals and compare orthopedic shoulder consultation and surgery rates.

Neural response patterns in spider, blood-injection-injury and social fearful individuals: new insights from a simultaneous EEG/ECG-fMRI study.

PubMed

Michałowski, Jarosław M; Matuszewski, Jacek; Droździel, Dawid; Koziejowski, Wojciech; Rynkiewicz, Andrzej; Jednoróg, Katarzyna; Marchewka, Artur

2017-06-01

In the present simultaneous EEG/ECG-fMRI study we compared the temporal and spatial characteristics of the brain responses and the cardiac activity during fear picture processing between spider, blood-injection-injury (BII) and social fearful as well as healthy (non-fearful) volunteers. All participants were presented with two neutral and six fear-related blocks of pictures: two social, two spider and two blood/injection fear blocks. In a social fear block neutral images were occasionally interspersed with photographs of angry faces and social exposure scenes. In spider and blood/injection fear blocks neutral pictures were interspersed with spider fear-relevant and blood/injection pictures, respectively. When compared to healthy controls the social fear group responded with increased activations in the anterior orbital, middle/anterior cingulate and middle/superior temporal areas for pictures depicting angry faces and with a few elevated superior frontal activations for social exposure scenes. In the blood/injection fear group, heart rate was decreased and the activity in the middle/inferior frontal and visual processing regions was increased for blood/injection pictures. The HR decrease for blood/injection pictures correlated with increased frontal responses. In the spider fear group, spider fear-relevant pictures triggered increased activations within a broad subcortical and cortical neural fear network. The HR response for spider fear-relevant stimuli was increased and correlated with an increased insula and hippocampus activity. When compared to healthy controls, all fear groups showed higher LPP amplitudes for their feared cues and an overall greater P1 hypervigilance effect. Contrasts against the fear control groups showed that the increased responses for fear-specific stimuli are mostly related to specific fears and not to general anxiety proneness. The results suggest different engagement of cognitive evaluation and down-regulation strategies and an overall increased sensitization of the fear system in the three fear groups.

Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula.

PubMed

Yang, Chengbo; Yang, Xiaojian; Lackeyram, Dale; Rideout, Todd C; Wang, Zirong; Stoll, Barbara; Yin, Yulong; Burrin, Douglas G; Fan, Ming Z

2016-06-01

Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA co-transporter (B(0)AT1, encoded by the SLC6A19 gene) plays a dominant role for apical uptake of large neutral AA including L-Gln, we hypothesized that high apical Na(+)-Gln co-transport activity, and B(0)AT1 (SLC6A19) in co-expression with angiotensin-converting enzyme 2 (ACE2) were expressed along the entire small intestinal crypt-villus axis in young animals via unique control mechanisms. Kinetics of Na(+)-Gln co-transport activity in the apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt-villus axis from liquid formula-fed young pigs, were measured with the membrane potential being clamped to zero using thiocyanate. Apical maximal Na(+)-Gln co-transport activity was much higher (p < 0.05) in the upper villus cells than in the middle villus (by 29 %) and the crypt (by 30 %) cells, whereas Na(+)-Gln co-transport affinity was lower (p < 0.05) in the upper villus cells than in the middle villus and the crypt cells. The B(0)AT1 (SLC6A19) mRNA abundance was lower (p < 0.05) in the crypt (by 40-47 %) than in the villus cells. There were no significant differences in B(0)AT1 and ACE2 protein abundances on the apical membrane among the upper villus, the middle villus and the crypt cells. Our study suggests that piglet fast growth is associated with very high intestinal apical Na(+)-neutral AA uptake activities via abundantly co-expressing B(0)AT1 and ACE2 proteins in the apical membrane and by transcribing the B(0)AT1 (SLC6A19) gene in the epithelia along the entire crypt-villus axis.

Force system evaluation of symmetrical beta-titanium T-loop springs preactivated by curvature and concentrated bends.

PubMed

Caldas, Sergei Godeiro Fernandes Rabelo; Martins, Renato Parsekian; Galvão, Marília Regalado; Vieira, Camilla Ivini Viana; Martins, Lídia Parsekian

2011-08-01

The objective of this research was to compare the effect of preactivation on the force system of beta-titanium T-loop springs (TLSs). Twenty TLSs with dimensions of 6 × 10 mm, of 0.017 × 0.025-in beta-titanium alloy, were randomly divided into 2 groups according to their preactivation. By using a moment transducer coupled to a digital extensometer indicator adapted to a testing machine, the amounts of horizontal force and moment produced were recorded at every 0.5 mm of deactivation from 5 mm of the initial activation in an interbracket distance of 23 mm. The moment-to-force ratio, the "neutral position" and the load-deflection ratio were also calculated. TLSs preactivated by curvature delivered horizontal forces significantly lower than those preactivated by concentrated bends. No differences were found in relation to the moments produced throughout the deactivation of both groups. The moment-to-force ratios were systematically higher on the TLSs preactivated by curvature than those preactivated by concentrated bends, except on 5 mm of activation. Significant differences were found in the load-deflection rates and "neutral position." The TLSs preactivated by curvature delivered lower horizontal forces and higher moment-to-force and load-deflection ratios than did those preactivated by concentrated bends. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Report for neutral buoyancy simulations of transfer orbit stage contingency extravehicular activities

NASA Technical Reports Server (NTRS)

Sexton, J. D.

1992-01-01

The transfer orbit stage (TOS) will propel the advanced communications technology satellite (ACTS) from the Space Shuttle to an Earth geosynchronous transfer orbit. Two neutral buoyancy test series were conducted at MSFC to validate the extravehicular activities (EVA) contingency operations for the ACTS/TOS/mission. The results of the neutral buoyancy tests are delineated and a brief history of the TOS EVA program is given.

Substance P levels and neutral endopeptidase activity in acute burn wounds and hypertrophic scar.

PubMed

Scott, Jeffrey R; Muangman, Pornprom R; Tamura, Richard N; Zhu, Kathy Q; Liang, Zhi; Anthony, Joanne; Engrav, Loren H; Gibran, Nicole S

2005-04-01

Substance P, a cutaneous neuroinflammatory mediator released from peripheral nerves, plays a role in responses to injury. Neutral endopeptidase is a cell membrane-bound metallopeptidase enzyme that regulates substance P activity. The question of substance P involvement in hypertrophic scar development has been based on observations that hypertrophic scars have increased numbers of nerves. The authors hypothesized that hypertrophic scar has greater substance P levels and decreased neutral endopeptidase activity compared with uninjured skin and acute partial-thickness burns, which may contribute to an exuberant response to injury. The authors obtained small skin samples of deep partial-thickness burns (n = 7; postburn days 7 to 78) and uninjured skin (n = 14) from patients (eight male patients and six female patients; 2 to 71 years old) undergoing burn wound excision. Hypertrophic scar samples were obtained from six patients (three male patients and three female patients; 8 to 47 years old) undergoing surgical excision 13 to 64 months after burn injury. Protein concentrations were determined using a bicinchoninic acid assay. Substance P concentration was determined by means of indirect enzyme-linked immunosorbent assay. Neutral endopeptidase activity was measured using an enzymatic assay that quantifies a fluorescent degradation product, methoxy-2-naphthylamine (MNA). Substance P and neutral endopeptidase data were standardized to sample weight. Substance P levels were greater in hypertrophic scar (3506 pg/g) compared with uninjured skin (1698 pg/g; p < 0.03) and burned skin (958 pg/g; p < 0.01). Hypertrophic scar samples had decreased neutral endopeptidase enzyme activity (8.8 pM MNA/hour/microg) compared with normal skin (16.3 pM MNA/hour/microg; p < 0.05). Acute burn wounds (27.9 pM MNA/hour/microg) demonstrated increased neutral endopeptidase enzyme activity (p < 0.05). Increased substance P concentration in hypertrophic scar correlates with histologic findings of increased nerve numbers in hypertrophic scar samples. Decreased neutral endopeptidase enzyme activity in hypertrophic scar may contribute to increased available substance P that may result in an exuberant neuroinflammatory response.

[Expression and characterization of a neutral Enterobacter cloacae GX-3 invertase].

PubMed

Zhao, Yingli; Wu, Qianqian; Zhang, Zhikai; Wang, Zilong; Wei, Yutuo; Huang, Ribo; Du, Liqin

2015-04-04

To characterize a neutral invertase from Enterobacter cloacae GX-3. By searching GenBank database, we found the genes encoding invertase from the same genus Enterobacter. These sequences were aligned and analyzed. Then, a gene encoding neutral invertase was amplified by PCR. The recombinant plasmid pQE-Einv was constructed. We purified the expressed protein Einv with nickel-nitrilotriacetic acid chromatography. At last, the characterics of the recombinant protein Einv were studied in detail. A gene encoding neutral invertase was discovered and cloned from E. cloacae GX-3. The recombinant enzyme Einv was characterized. Einv had an optimum pH of 6.5 and an optimum temperature of 40 degrees C. The results of sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE) and gel permeation chromatography ( GPC) showed that Einv was a homo-dimer protein. Einv retained 80% activity at sucrose concentrations up to 1170 mmol/L. But, Einv had no transglycosylation activity at high sucrose concentration. It could hydrolyze raffinose, 1-kestose, nystose, fructofuranosylnystose and stachyose. It is first reported that an invertase from Enterobacter cloacae is a beta-fructofuranosidase at neutral pH range. It only has hydrolysis activity without tranglycosylation activity. These characteristics indicate that the neutral invertase Einv has important applications in food industry.

Recombinant cathepsin E has no proteolytic activity at neutral pH.

PubMed

Zaidi, Nousheen; Herrmann, Timo; Voelter, Wolfgang; Kalbacher, Hubert

2007-08-17

Cathepsin E (CatE) is a major intracellular aspartic protease reported to be involved in cellular protein degradation and several pathological processes. Distinct cleavage specificities of CatE at neutral and acidic pH have been reported previously in studies using CatE purified from human gastric mucosa. Here, in contrast, we have analyzed the proteolytic activity of recombinant CatE at acidic and neutral pH using two separate approaches, RP-HPLC and FRET-based proteinase assays. Our data clearly indicate that recombinant CatE does not possess any proteolytic activity at all at neutral pH and was unable to cleave the peptides glucagon, neurotensin, and dynorphin A that were previously reported to be cleaved by CatE at neutral pH. Even in the presence of ATP, which is known to stabilize CatE, no proteolytic activity was observed. These discrepant results might be due to some contaminating factor present in the enzyme preparations used in previous studies or may reflect differences between recombinant CatE and the native enzyme.

Development of a High-Content Orthopoxvirus Infectivity and Neutralization Assays

PubMed Central

Gates, Irina; Olson, Victoria; Smith, Scott; Patel, Nishi; Damon, Inger; Karem, Kevin

2015-01-01

Currently, a number of assays measure Orthopoxvirus neutralization with serum from individuals, vaccinated against smallpox. In addition to the traditional plaque reduction neutralization test (PRNT), newer higher throughput assays are based on neutralization of recombinant vaccinia virus, expressing reporter genes such as β-galactosidase or green fluorescent protein. These methods could not be used to evaluate neutralization of variola virus, since genetic manipulations of this virus are prohibited by international agreements. Currently, PRNT is the assay of choice to measure neutralization of variola virus. However, PRNT assays are time consuming, labor intensive, and require considerable volume of serum sample for testing. Here, we describe the development of a high-throughput, cell-based imaging assay that can be used to measure neutralization, and characterize replication kinetics of various Orthopoxviruses, including variola, vaccinia, monkeypox, and cowpox. PMID:26426117

The Receptor-Binding Site of the Measles Virus Hemagglutinin Protein Itself Constitutes a Conserved Neutralizing Epitope

PubMed Central

Ohno, Shinji; Sakai, Kouji; Ito, Yuri; Fukuhara, Hideo; Komase, Katsuhiro; Brindley, Melinda A.; Rota, Paul A.; Plemper, Richard K.; Maenaka, Katsumi; Takeda, Makoto

2013-01-01

Here, we provide direct evidence that the receptor-binding site of measles virus (MV) hemagglutinin protein itself forms an effective conserved neutralizing epitope (CNE). Several receptor-interacting residues constitute the CNE. Thus, viral escape from neutralization has to be associated with loss of receptor-binding activity. Since interactions with both the signaling lymphocyte activation molecule (SLAM) and nectin4 are critical for MV pathogenesis, its escape, which results from loss of receptor-binding activity, should not occur in nature. PMID:23283964

Glenohumeral Function of the Long Head of the Biceps Muscle

PubMed Central

Chalmers, Peter N.; Cip, Johannes; Trombley, Robert; Cole, Brian J.; Wimmer, Markus A.; Romeo, Anthony A.; Verma, Nikhil N.

2014-01-01

Background: Optimal treatment of superior labral anterior-posterior (SLAP) tears is controversial, in part because the dynamic role of the long head of the biceps muscle (LHBM) in the glenohumeral joint is unclear. The aim of this study was to determine dynamic LHBM behavior during shoulder activity by studying (1) the electromyographic activity of the LHBM during shoulder motion, (2) the effect of elbow immobilization on this activity, and (3) the effect of a load applied to the distal humerus on this activity. Hypothesis: The LHBM would not play a significant role in active glenohumeral range of motion. Study Design: Controlled laboratory study. Methods: Thirteen normal volunteers underwent surface electromyography (EMG) measurement of the LHBM, short head biceps muscle (SHBM), deltoid, infraspinatus, and brachioradialis during shoulder motion from the neutral position (0° of rotation, flexion, and abduction) to 45° of flexion, 90° of flexion, 45° of abduction, and 90° of abduction. These motions were repeated both with and without splint immobilization of the forearm and elbow at 100° of flexion and neutral rotation and with and without a 1-kg weight placed on the lateral distal humerus. Results: Mean EMG activity within the LHBM and the SHBM was low (≤11.6% ± 9.1%). LHBM activity was significant increased by flexion and abduction (P < .049 in all cases), while SHBM activity was not. EMG activity from the middle head of the deltoid was significantly increased by loading with the shoulder positioned away from the body (ie, in abduction or flexion). When compared with the unloaded state, the addition of a distal humeral load significantly increased LHBM activity in 45° of abduction (P = .028) and 90° of flexion (P = .033) despite forearm and elbow immobilization. The SHBM showed similar trends. Conclusion: In normal volunteers with forearm and elbow immobilization and application of a load to the distal humerus, LHBM EMG activity is increased by both glenohumeral flexion and abduction, suggesting that this muscle plays a dynamic role in glenohumeral motion with higher demand activities. Clinical Relevance: Biceps tenodesis may result in dynamic change within the glenohumeral joint with higher demand activities. PMID:26535304

Three-dimensional modeling of the neutral gas depletion effect in a helicon discharge plasma

NASA Astrophysics Data System (ADS)

Kollasch, Jeffrey; Schmitz, Oliver; Norval, Ryan; Reiter, Detlev; Sovinec, Carl

2016-10-01

Helicon discharges provide an attractive radio-frequency driven regime for plasma, but neutral-particle dynamics present a challenge to extending performance. A neutral gas depletion effect occurs when neutrals in the plasma core are not replenished at a sufficient rate to sustain a higher plasma density. The Monte Carlo neutral particle tracking code EIRENE was setup for the MARIA helicon experiment at UW Madison to study its neutral particle dynamics. Prescribed plasma temperature and density profiles similar to those in the MARIA device are used in EIRENE to investigate the main causes of the neutral gas depletion effect. The most dominant plasma-neutral interactions are included so far, namely electron impact ionization of neutrals, charge exchange interactions of neutrals with plasma ions, and recycling at the wall. Parameter scans show how the neutral depletion effect depends on parameters such as Knudsen number, plasma density and temperature, and gas-surface interaction accommodation coefficients. Results are compared to similar analytic studies in the low Knudsen number limit. Plans to incorporate a similar Monte Carlo neutral model into a larger helicon modeling framework are discussed. This work is funded by the NSF CAREER Award PHY-1455210.

Mercury Inhibits Soil Enzyme Activity in a Lower Concentration than the Guideline Value.

PubMed

Mahbub, Khandaker Rayhan; Krishnan, Kannan; Megharaj, Mallavarapu; Naidu, Ravi

2016-01-01

Three soil types - neutral, alkaline and acidic were experimentally contaminated with nine different concentrations of inorganic mercury (0, 5, 10, 50, 100, 150, 200, 250, 300 mg/kg) to derive effective concentrations of mercury that exert toxicity on soil quality. Bioavailability of mercury in terms of water solubility was lower in acidic soil with higher organic carbon. Dehydrogenase enzyme activity and nitrification rate were chosen as indicators to assess soil quality. Inorganic mercury significantly inhibited (p < 0.001) microbial activities in the soils. The critical mercury contents (EC10) were found to be less than the available safe limits for inorganic mercury which demonstrated inadequacy of existing guideline values.

[FAB immunoglobulin fragments. I. The comparative characteristics of the serological and virus-neutralizing properties of a gamma globulin against tick-borne encephalitis and of the FAB fragments isolated from it].

PubMed

Barban, P S; Minaeva, V M; Pantiukhina, A N; Startseva, M G

1976-06-01

A comparative study was made of the serological properties and virus-neutralizing activity of antiencephalitis gamma-globulin and Fab-fragments isolated from it by gel-filtration. Horse immunoglobulins against the autumno-summer tick-borne encephalitis virus could be disintegrated with the aid of papaine to monovalent Fab-fragments which (according to the complement fixation reaction, the test of suppression of the complement fixation, and the HAIT) retained the serological activity whose level was compared with that of the serological activity of gamma-globulin. Fab-fragments possessed a marked virus-neutralizing activity. The mean value of a logarithm of the neutralization index was 2.65 +/- 0.2 for Fab-fragments and 3.74 +/- 0.38 for gamma-globulin (P less than 0.01).

Female Emotional Eaters Show Abnormalities in Consummatory and Anticipatory Food Reward

PubMed Central

Bohon, Cara; Stice, Eric; Spoor, Sonja

2009-01-01

Objective To test the hypothesis that emotional eaters show greater neural activation in response to food intake and anticipated food intake than nonemotional eaters and whether these differences are amplified during a negative versus neutral mood state. Method Female emotional eaters and nonemotional eaters (N = 21) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless control solution while in a negative and neutral mood. Results Emotional eaters showed greater activation in the parahippocampal gyrus and anterior cingulate (ACC) in response to anticipated receipt of milkshake and greater activation in the pallidum, thalamus, and ACC in response to receipt of milkshake during a negative relative to a neutral mood. In contrast, nonemotional eaters showed decreased activation in reward regions during a negative versus a neutral mood. Discussion Results suggest that emotional eating is related to increased anticipatory and consummatory food reward, but only during negative mood. PMID:19040270

Impacts of motivational valence on the error-related negativity elicited by full and partial errors.

PubMed

Maruo, Yuya; Schacht, Annekathrin; Sommer, Werner; Masaki, Hiroaki

2016-02-01

Affect and motivation influence the error-related negativity (ERN) elicited by full errors; however, it is unknown whether they also influence ERNs to correct responses accompanied by covert incorrect response activation (partial errors). Here we compared a neutral condition with conditions, where correct responses were rewarded or where incorrect responses were punished with gains and losses of small amounts of money, respectively. Data analysis distinguished ERNs elicited by full and partial errors. In the reward and punishment conditions, ERN amplitudes to both full and partial errors were larger than in the neutral condition, confirming participants' sensitivity to the significance of errors. We also investigated the relationships between ERN amplitudes and the behavioral inhibition and activation systems (BIS/BAS). Regardless of reward/punishment condition, participants scoring higher on BAS showed smaller ERN amplitudes in full error trials. These findings provide further evidence that the ERN is related to motivational valence and that similar relationships hold for both full and partial errors. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Application of subtracted gDNA microarray-assisted Bulked Segregant Analysis for rapid discovery of molecular markers associated with day-neutrality in strawberry (Fragaria x ananassa)

PubMed Central

Gor, Mian Chee; Mantri, Nitin; Pang, Edwin

2016-01-01

A Fragaria Discovery Panel (FDP; strawberry-specific SDA) containing 287 features was constructed by subtracting the pooled gDNA of nine non-angiosperm species from the pooled gDNA of five strawberry genotypes. This FDP was used for Bulk Segregant Analysis (BSA) to enable identification of molecular markers associated with day-neutrality. Analysis of hybridisation patterns of a short day (SD) DNA bulk and three day-neutral (DN) DNA bulks varying in flowering strength allowed identification of a novel feature, FaP2E11, closely linked to CYTOKININ OXIDASE 1 (CKX1) gene possibly involved in promoting flowering under non-inductive condition. The signal intensities of FaP2E11 feature obtained from the strong DN bulk (DN1) is three fold higher than the short day bulk (SD), indicating that the putative marker may linked to a CKX1 variant allele with lower enzyme activity. We propose a model for flowering regulation based on the hypothesis that flowering strength may be regulated by the copy number of FaP2E11-linked CKX1 alleles. This study demonstrates the feasibility of the SDA-based BSA approach for the identification of molecular markers associated with day-neutrality in strawberry. This innovative strategy is an efficient and cost-effective approach for molecular marker discovery. PMID:27586242

Changes in sugar content and related enzyme activities in table grape (Vitis vinifera L.) in response to foliar selenium fertilizer.

PubMed

Zhu, Shuaimeng; Liang, Yinli; An, Xiaojuan; Kong, Fanchao; Gao, Dekai; Yin, Hongfei

2017-09-01

Spraying selenium (Se) fertilizer is an effective method for Se-enriched fruit production. Sugar content in fruit is the major factor determining berry quality. However, changes in sugar metabolism in response to Se fertilizer are unclear. Hence, this study was conducted to identify the effects of Se fertilizer on sugar metabolism and related enzyme activities of grape berries. Additionally, production of leaves with and without Se fertilizer was also investigated. Acid invertase (AI) activity, total soluble sugar and Se content in berries, and photosynthetic rate in leaves produced under Se fertilizer treatments were higher than that of control. Glucose and fructose were the primary sugars in berries, with a trace of sucrose. In both berries and leaves, neutral invertase activity was lower than AI, there was no significant difference in neutral invertase, sucrose synthase and sucrose phosphate synthase between Se fertilizer-treated and control. In berries, AI showed a significant positive correlation with glucose and fructose; also Se content was significantly correlated with sugar content. AI played an important role in the process of sugar accumulation in berries; high AI activity in berries and photosynthetic rate in leaves could explain the mechanism by which Se fertilizer affected sugar accumulation in berries. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The effect of emotionally valenced eye region images on visuocortical processing of surprised faces.

PubMed

Li, Shuaixia; Li, Ping; Wang, Wei; Zhu, Xiangru; Luo, Wenbo

2018-05-01

In this study, we presented pictorial representations of happy, neutral, and fearful expressions projected in the eye regions to determine whether the eye region alone is sufficient to produce a context effect. Participants were asked to judge the valence of surprised faces that had been preceded by a picture of an eye region. Behavioral results showed that affective ratings of surprised faces were context dependent. Prime-related ERPs with presentation of happy eyes elicited a larger P1 than those for neutral and fearful eyes, likely due to the recognition advantage provided by a happy expression. Target-related ERPs showed that surprised faces in the context of fearful and happy eyes elicited dramatically larger C1 than those in the neutral context, which reflected the modulation by predictions during the earliest stages of face processing. There were larger N170 with neutral and fearful eye contexts compared to the happy context, suggesting faces were being integrated with contextual threat information. The P3 component exhibited enhanced brain activity in response to faces preceded by happy and fearful eyes compared with neutral eyes, indicating motivated attention processing may be involved at this stage. Altogether, these results indicate for the first time that the influence of isolated eye regions on the perception of surprised faces involves preferential processing at the early stages and elaborate processing at the late stages. Moreover, higher cognitive processes such as predictions and attention can modulate face processing from the earliest stages in a top-down manner. © 2017 Society for Psychophysiological Research.

A functional magnetic resonance imaging investigation of short-term source and item memory for negative pictures.

PubMed

Mitchell, Karen J; Mather, Mara; Johnson, Marcia K; Raye, Carol L; Greene, Erich J

2006-10-02

We investigated the hypothesis that arousal recruits attention to item information, thereby disrupting working memory processes that help bind items to context. Using functional magnetic resonance imaging, we compared brain activity when participants remembered negative or neutral picture-location conjunctions (source memory) versus pictures only. Behaviorally, negative trials showed disruption of short-term source, but not picture, memory; long-term picture recognition memory was better for negative than for neutral pictures. Activity in areas involved in working memory and feature integration (precentral gyrus and its intersect with superior temporal gyrus) was attenuated on negative compared with neutral source trials relative to picture-only trials. Visual processing areas (middle occipital and lingual gyri) showed greater activity for negative than for neutral trials, especially on picture-only trials.

A fully human monoclonal antibody with novel binding epitope and excellent neutralizing activity to multiple human IFN-α subtypes: A candidate therapy for systemic lupus erythematosus.

PubMed

Du, Peng; Xu, Lei; Qiu, Weiyi; Zeng, Dadi; Yue, Junjie; Wang, Shuang; Huang, Peitang; Sun, Zhiwei

2015-01-01

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease short of effective therapeutic agents. A multitude of studies of SLE in the last decade have accentuated a central role of the interferon alpha (IFN-α) pathway in SLE pathogenesis. We report here a candidate therapeutic neutralizing antibody, AIA22, with a different binding epitope and discrepant neutralizing profile from the anti-multiple IFN-α subtype antibodies currently in clinical trials. AIA22 specifically interacts with multiple IFN-α subtypes, binds to the type I IFN receptor 2 (IFNAR2) recognition region of IFN-α (considered a novel antigen epitope), and effectively neutralizes the activity of almost all of the IFN-α subtypes (with the exception of IFN-α7) both in vitro and in vivo. Concurrently, structural modeling and computational design yielded a mutational antibody of AIA22, AIAmut, which exhibited substantially improved neutralizing activity to multiple IFN-α subtypes.

Neutralization of Yersinia pestis-mediated macrophage cytotoxicity by anti-LcrV antibodies and its correlation with protective immunity in a mouse model of bubonic plague.

PubMed

Zauberman, Ayelet; Cohen, Sara; Levy, Yinon; Halperin, Gideon; Lazar, Shirley; Velan, Baruch; Shafferman, Avigdor; Flashner, Yehuda; Mamroud, Emanuelle

2008-03-20

Plague is a life-threatening disease caused by Yersinia pestis, for which effective-licensed vaccines and reliable predictors of in vivo immunity are lacking. V antigen (LcrV) is a major Y. pestis virulence factor that mediates translocation of the cytotoxic Yersinia protein effectors (Yops). It is a well-established protective antigen and a part of currently tested plague subunit vaccines. We have developed a highly sensitive in vitro macrophage cytotoxicity neutralization assay which is mediated by anti-LcrV antibodies; and studied the potential use of these neutralizing antibodies as an in vitro correlate of plague immunity in mice. The assay is based on a Y. pestis strain with enhanced cytotoxicity to macrophages in which endogenous yopJ was replaced by the more effectively translocated yopP of Y. enterocolitica O:8. Mice passively immunized with rabbit anti-LcrV IgG or actively immunized with recombinant LcrV were protected against lethal doses of a virulent Y. pestis strain, in a mouse model of bubonic plague. This protection significantly correlated with the in vitro neutralizing activity of the antisera but not with their corresponding ELISA titers. In actively immunized mice, a cutoff value for serum neutralizing activity, above which survival was assured with high degree of confidence, could be established for different vaccination regimes. The impact of overall findings on the potential use of serum neutralizing activity as a correlate of protective immunity is discussed.

Neural Mechanisms of Reading Facial Emotions in Young and Older Adults

PubMed Central

Ebner, Natalie C.; Johnson, Marcia K.; Fischer, Håkan

2012-01-01

The ability to read and appropriately respond to emotions in others is central for successful social interaction. Young and older adults are better at identifying positive than negative facial expressions and also expressions of young than older faces. Little, however, is known about the neural processes associated with reading different emotions, particularly in faces of different ages, in samples of young and older adults. During fMRI, young and older participants identified expressions in happy, neutral, and angry young and older faces. The results suggest a functional dissociation of ventromedial prefrontal cortex (vmPFC) and dorsomedial prefrontal cortex (dmPFC) in reading facial emotions that is largely comparable in young and older adults: Both age groups showed greater vmPFC activity to happy compared to angry or neutral faces, which was positively correlated with expression identification for happy compared to angry faces. In contrast, both age groups showed greater activity in dmPFC to neutral or angry than happy faces which was negatively correlated with expression identification for neutral compared to happy faces. A similar region of dmPFC showed greater activity for older than young faces, but no brain-behavior correlations. Greater vmPFC activity in the present study may reflect greater affective processing involved in reading happy compared to neutral or angry faces. Greater dmPFC activity may reflect more cognitive control involved in decoding and/or regulating negative emotions associated with neutral or angry than happy, and older than young, faces. PMID:22798953

Pyrazole derived ultra-short antimicrobial peptidomimetics with potent anti-biofilm activity.

PubMed

Ahn, Mija; Gunasekaran, Pethaiah; Rajasekaran, Ganesan; Kim, Eun Young; Lee, Soo-Jae; Bang, Geul; Cho, Kun; Hyun, Jae-Kyung; Lee, Hyun-Ju; Jeon, Young Ho; Kim, Nam-Hyung; Ryu, Eun Kyoung; Shin, Song Yub; Bang, Jeong Kyu

2017-01-05

In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin. Besides its higher selectivity (therapeutic index) toward bacterial cells than LL-37, Py11 showed highly increased proteolytic stability against trypsin digestion and maintained its antimicrobial activity in the presence of physiological salts. Interestingly, Py11 exhibited higher anti-biofilm activity against MDRPA compared to LL-37. The results from fluorescence spectroscopy and transmission electron microscopy (TEM) suggested that Py11 kills bacterial cells possibly by integrity disruption damaging the cell membrane, leading to the cytosol leakage and eventual cell lysis. Furthermore, Py11 displayed significant anti-inflammatory (endotoxin-neutralizing) activity by inhibiting LPS-induced production of nitric oxide (NO) and TNF-α. Collectively, our results suggest that Py11 may serve as a model compound for the design of antimicrobial and antisepsis agents. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

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

Bates, John T.; Keefer, Christopher J.; Slaughter, James C.

2014-04-15

The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on}more » with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.« less

Binding neutral information to emotional contexts: Brain dynamics of long-term recognition memory.

PubMed

Ventura-Bort, Carlos; Löw, Andreas; Wendt, Julia; Moltó, Javier; Poy, Rosario; Dolcos, Florin; Hamm, Alfons O; Weymar, Mathias

2016-04-01

There is abundant evidence in memory research that emotional stimuli are better remembered than neutral stimuli. However, effects of an emotionally charged context on memory for associated neutral elements is also important, particularly in trauma and stress-related disorders, where strong memories are often activated by neutral cues due to their emotional associations. In the present study, we used event-related potentials (ERPs) to investigate long-term recognition memory (1-week delay) for neutral objects that had been paired with emotionally arousing or neutral scenes during encoding. Context effects were clearly evident in the ERPs: An early frontal ERP old/new difference (300-500 ms) was enhanced for objects encoded in unpleasant compared to pleasant and neutral contexts; and a late central-parietal old/new difference (400-700 ms) was observed for objects paired with both pleasant and unpleasant contexts but not for items paired with neutral backgrounds. Interestingly, objects encoded in emotional contexts (and novel objects) also prompted an enhanced frontal early (180-220 ms) positivity compared to objects paired with neutral scenes indicating early perceptual significance. The present data suggest that emotional--particularly unpleasant--backgrounds strengthen memory for items encountered within these contexts and engage automatic and explicit recognition processes. These results could help in understanding binding mechanisms involved in the activation of trauma-related memories by neutral cues.

MSFC Skylab neutral buoyancy simulator

NASA Technical Reports Server (NTRS)

1974-01-01

The use of a neutral buoyancy simulator for developing extravehicular activity systems and for training astronauts in weightless activities is discussed. The construction of the facility and the operations are described. The types of tests and the training activities conducted in the simulator are reported. Photographs of the components of the simulator and actual training exercises are included.

Friend Leukemogenic Virus-neutralizing Antibody from Mouse Ascitic Fluid

PubMed Central

March, R. W.; Chirigos, M. A.; Hook, W. A.; Burka, B. L.

1967-01-01

Ascitic fluid antibody produced in C57/B1 mice immunized with Friend leukemogenic virus exhibited potent neutralizing activity. In vitro neutralization tests revealed that a mean neutralization index of 3.0 was achieved, and it was shown by sucrose gradient ultracentrifugation that this antibody resembled the 7S type. A mean yield of 6.7 ml of fluid per mouse per weekly paracentesis was obtained over an 8-week period. The ascitic fluid antibody to Friend virus was also active in vivo. Mice given antibody 3, 5, 7, and 9 days after infection with Friend virus did not develop the splenomegaly characteristic of Friend disease. PMID:16349755

Dye-release assay for investigation of antimicrobial peptide activity in a competitive lipid environment.

PubMed

Sani, Marc-Antoine; Gagne, Eve; Gehman, John D; Whitwell, Thomas C; Separovic, Frances

2014-09-01

A dye-release method for investigating the effect of a competitive lipid environment on the activity of two membrane-disrupting antimicrobial peptides (AMP), maculatin 1.1 and aurein 1.2, is presented. The results support the general conclusion that AMP have greater affinity for negatively charged membranes, for example bacterial membranes, than for the neutral membrane surface found in eukaryotic cells, but only within a competitive lipid environment. Indeed, in a single-model membrane environment, both peptides were more potent against neutral vesicles than against charged vesicles. The approach was also used to investigate the effect of pre-incubating the peptides in a neutral lipid environment then introducing charged lipid vesicles. Maculatin was shown to migrate from the neutral lipid bilayers, where pores had already formed, to the charged membrane bilayers. This result was also observed for charged-to-charged bilayers but, interestingly, not for neutral-to-neutral lipid interfaces. Aurein was able to migrate from either lipid environment, indicating weaker binding to lipid membranes, and a different molecular mechanism for lysis of lipid bilayers. Competitive lipid environments could be used to assess other critical conditions that modulate the activity of membrane peptides or proteins.

Analytical Method for the Detection of Residual Active Ingredients Found in Neutralized Suspensions of Antimicrobial Products.

PubMed

Kamel, Alaa; Tomasino, Stephen F

2017-03-01

An analytical method for determining the presence and levels of residual active ingredients found in neutralized suspensions of phenolic and quaternary ammonium salt-based antimicrobial products was developed using solid-phase extraction in combination with LC-tandem MS. A single-laboratory validation of the method was performed at three concentration levels for the quaternary ammonium compounds (also referred to as benzalkonium chlorides or BACs) and the phenols in the presence of letheen broth neutralizer at 2.5 and 2.75 μg/mL, respectively, as well as at dilutions of 1:10 and 1:100 in those concentrations. The method's lowest LODs were 0.005 μg/g for BACs and 0.006 μg/g for phenols. The average recovery of the fortified samples for both active ingredients ranged between 80 and 124%, and RSDs were generally <20%. In a related study, the effectiveness of letheen broth with and without sodium thiosulfate was evaluated as a neutralizer for sodium hypochlorite. The results showed that letheen broth without sodium thiosulfate neutralizes chlorine concentrations up to 60 ppm, and that 200 μg sodium thiosulfate are required to neutralize a 72 ppm concentrated chlorine solution in letheen broth.

Characterization of Alpha-Toxin hla Gene Variants, Alpha-Toxin Expression Levels, and Levels of Antibody to Alpha-Toxin in Hemodialysis and Postsurgical Patients with Staphylococcus aureus Bacteremia

PubMed Central

Wu, Yuling; Tabor, David E.; Mok, Hoyin; Sellman, Bret R.; Jenkins, Amy; Yu, Li; Jafri, Hasan S.; Rude, Thomas H.; Ruffin, Felicia; Schell, Wiley A.; Park, Lawrence P.; Yan, Qin; Thaden, Joshua T.; Messina, Julia A.; Esser, Mark T.

2014-01-01

Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent spa typing and hla sequencing. Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha-toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay. Most isolates encoded hla (197/200; 98.5%) and expressed alpha-toxin (173/200; 86.5%). In vitro alpha-toxin levels were inversely associated with survival (cure, 2.19 μg/ml, versus failure, 1.09 μg/ml; P < 0.01). Both neutralizing (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing S. aureus isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of hla revealed 12 distinct hla genotypes, and all genotypic variants were susceptible to a neutralizing monoclonal antibody in clinical development (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in clinical S. aureus isolates. Higher in vitro alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study. PMID:25392350

Neutral-Line Magnetic Shear and Enhanced Coronal Heating in Solar Active Regions

NASA Technical Reports Server (NTRS)

Falconer, D. A.; Moore, R. L.; Porter, J. G.; Gary, G. A.; Shimizu, T.

1997-01-01

By examining the magnetic structure at sites in the bright coronal interiors of active regions that are not flaring but exhibit persistent strong coronal heating, we establish some new characteristics of the magnetic origins of this heating. We have examined the magnetic structure of these sites in five active regions, each of which was well observed by both the Yohkoh SXT and the Marshall Space Flight Center Vector Magnetograph and showed strong shear in its magnetic field along part of at least one neutral line (polarity inversion). Thus, we can assess whether this form of nonpotential field structure in active regions is a characteristic of the enhanced coronal heating and vice versa. From 27 orbits' worth of Yohkoh SXT images of the five active regions, we have obtained a sample of 94 persistently bright coronal features (bright in all images from a given orbit), 40 long (greater than or approximately equals 20,000 km) neutral-line segments having strong magnetic shear throughout (shear angle greater than 45 deg), and 39 long neutral-line segments having weak magnetic shear throughout (shear angle less than 45 deg). From this sample, we find that: (1) all of our persistently bright coronal features are rooted in magnetic fields that are stronger than 150 G; (2) nearly all (95%) of these enhanced coronal features are rooted near neutral lines (closer than 10,000 km); (3) a great majority (80%) of the bright features are rooted near strong-shear portions of neutral lines; (4) a great majority (85%) of long strong-shear segments of neutral lines have persistently bright coronal features rooted near them; (5) a large minority (40%) of long weak-shear segments of neutral lines have persistently bright coronal features rooted near them; and (6) the brightness of a persistently bright Coronal feature often changes greatly over a few hours. From these results, we conclude that most persistent enhanced heating of coronal loops in active regions: (1) requires the presence of a polarity inversion in the magnetic field near at least one of the loop footpoints; (2) is greatly aided by the presence of strong shear in the core magnetic field along that neutral line; and (3) is controlled by some variable process that acts in this magnetic environment. We infer that this variable process is low-lying reconnection accompanying flux cancellation.

Expression of enhancing-activity-free neutralizing antibody against dengue type 1 virus in plasmid-inoculated mice.

PubMed

Yamanaka, Atsushi; Pitaksajjakul, Pannamthip; Ramasoota, Pongrama; Konishi, Eiji

2015-11-09

Most candidate dengue vaccines currently under development induce neutralizing antibodies, which are considered important for immunoprotection. However, the concomitant induction of infection-enhancing antibodies is an unavoidable concern. In contrast, a neutralizing antibody developed for passive immunotherapy has been engineered to eliminate its enhancing activity. Therefore, a strategy for the long-term expression of enhancing-activity-free neutralizing antibodies may resolve this concern. A mouse monoclonal antibody, 7F4, of the IgG3 subclass and with no detectable enhancing activity, was selected as the model neutralizing antibody to evaluate the potential of this strategy. Equal amounts of commercial vector (pFUSE)-based plasmids containing 7F4 heavy (H)- or light (L)-chain variable region genes were mixed and used for the cotransfection of 293T cells and co-delivery into ICR and BALB/c mice. The recombinant plasmids were designed to express IgG2b or IgG3 subclass antibodies (p7F4G2b or p7F4G3, respectively). 293T cells transfected with 2 μg of p7F4G2b or p7F4G3 produced approximately 15,000 or 800 ng/ml IgG in the culture fluids, respectively. The dose is expressed as the total amount of H- and L-chain plasmids. Neutralizing antibody was detected dose-dependently in ICR mice inoculated with 50-200 μg of p7F4G2b. A 1:2 dilution of sera from ICR and BALB/c mice inoculated with 100 μg of p7F4G3 showed average plaque reduction levels of >70% on day 3 and >90% on days 5-9. BALB/c mice maintained detectable neutralizing antibody for at least 3 months. The neutralizing antibody expressed by p7F4G3 in mice showed no enhancing activity. Although the expression of neutralizing antibodies from immunoglobulin genes is a type of passive immunization, its durability can be utilized as a dengue vaccine strategy. This "proof-of-concept" study using a mouse model demonstrates that the enhancing-activity-free characteristic of this strategy augurs well for dengue vaccine development, although further improvement is required. Copyright © 2015 Elsevier Ltd. All rights reserved.

7. LESLIE WICKMAN, EVA (EXTRA VEHICULAR ACTIVITIES) SPECIALIST, IN SPACE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. LESLIE WICKMAN, EVA (EXTRA VEHICULAR ACTIVITIES) SPECIALIST, IN SPACE SUIT AFTER TESTING IN NEUTRAL BUOYANCY TANK. AVERAGE COST OF SUIT IS $1,000,000. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

Snake venom neutralization by Indian medicinal plants (Vitex negundo and Emblica officinalis) root extracts.

PubMed

Alam, M I; Gomes, A

2003-05-01

The methanolic root extracts of Vitex negundo Linn. and Emblica officinalis Gaertn. were explored for the first time for antisnake venom activity. The plant (V. negundo and E. officinalis) extracts significantly antagonized the Vipera russellii and Naja kaouthia venom induced lethal activity both in in vitro and in vivo studies. V. russellii venom-induced haemorrhage, coagulant, defibrinogenating and inflammatory activity was significantly neutralized by both plant extracts. No precipitating bands were observed between the plant extract and snake venom. The above observations confirmed that the plant extracts possess potent snake venom neutralizing capacity and need further investigation.

Airway response to emotion- and disease-specific films in asthma, blood phobia, and health.

PubMed

Ritz, Thomas; Wilhelm, Frank H; Meuret, Alicia E; Gerlach, Alexander L; Roth, Walton T

2011-01-01

Earlier research found autonomic and airway reactivity in asthma patients when they were exposed to blood-injection-injury (BII) stimuli. We studied oscillatory resistance (R(os)) in asthma and BII phobia during emotional and disease-relevant films and examined whether muscle tension counteracts emotion-induced airway constriction. Fifteen asthma patients, 12 BII phobia patients, and 14 healthy controls viewed one set of negative, positive, neutral, BII-related, and asthma-related films with leg muscle tension and a second set without. R(os), ventilation, cardiovascular activity, and skin conductance were measured continuously. R(os) was higher during emotional compared to neutral films, particularly during BII material, and responses increased from healthy over asthmatic to BII phobia participants. Leg muscle tension did not abolish R(os) increases. Thus, the airways are particularly responsive to BII-relevant stimuli, which could become risk factors for asthma patients. Copyright © 2010 Society for Psychophysiological Research.

Diet and fecal steroid profile in a South Asian population with a low colon-cancer rate.

PubMed

McKeigue, P M; Adelstein, A M; Marmot, M G; Henly, P J; Owen, R W; Hill, M J; Thompson, M H

1989-07-01

South Asian immigrants to England and Wales have low mortality from colon cancer and high mortality from coronary heart disease compared with the general population. In a survey of a predominantly Gujarati population in northwest London, both vegetarians and nonvegetarians had similar total dietary fat intake to the native British population but higher dietary fiber intake. Total fecal bile acid and neutral animal sterol concentrations were lower in South Asians than in a native British comparison group. Sixty-two percent of South Asians excreted detectable quantities of free primary bile acids, which were not present in stools from native British subjects. The ratio of fecal coprostanol to total neutral animal sterols was also lower in South Asians. Low risk of colon cancer in this population may be related to reduced microbial activity in the bowel and low levels of tumor-promoting secondary bile acids.

Highlighting relatedness promotes prosocial motives and behavior.

PubMed

Pavey, Louisa; Greitemeyer, Tobias; Sparks, Paul

2011-07-01

According to self-determination theory, people have three basic psychological needs: relatedness, competence, and autonomy. Of these, the authors reasoned that relatedness need satisfaction is particularly important for promoting prosocial behavior because of the increased sense of connectedness to others that this engenders. In Experiment 1, the authors manipulated relatedness, autonomy, competence, or gave participants a neutral task, and found that highlighting relatedness led to higher interest in volunteering and intentions to volunteer relative to the other conditions. Experiment 2 found that writing about relatedness experiences promoted feelings of connectedness to others, which in turn predicted greater prosocial intentions. Experiment 3 found that relatedness manipulation participants donated significantly more money to charity than did participants given a neutral task. The results suggest that highlighting relatedness increases engagement in prosocial activities and are discussed in relation to the conflict and compatibility between individual and social outcomes. © 2011 by the Society for Personality and Social Psychology, Inc

Graded Neuronal Modulations Related to Visual Spatial Attention.

PubMed

Mayo, J Patrick; Maunsell, John H R

2016-05-11

Studies of visual attention in monkeys typically measure neuronal activity when the stimulus event to be detected occurs at a cued location versus when it occurs at an uncued location. But this approach does not address how neuronal activity changes relative to conditions where attention is unconstrained by cueing. Human psychophysical studies have used neutral cueing conditions and found that neutrally cued behavioral performance is generally intermediate to that of cued and uncued conditions (Posner et al., 1978; Mangun and Hillyard, 1990; Montagna et al., 2009). To determine whether the neuronal correlates of visual attention during neutral cueing are similarly intermediate, we trained macaque monkeys to detect changes in stimulus orientation that were more likely to occur at one location (cued) than another (uncued), or were equally likely to occur at either stimulus location (neutral). Consistent with human studies, performance was best when the location was cued, intermediate when both locations were neutrally cued, and worst when the location was uncued. Neuronal modulations in visual area V4 were also graded as a function of cue validity and behavioral performance. By recording from both hemispheres simultaneously, we investigated the possibility of switching attention between stimulus locations during neutral cueing. The results failed to support a unitary "spotlight" of attention. Overall, our findings indicate that attention-related changes in V4 are graded to accommodate task demands. Studies of the neuronal correlates of attention in monkeys typically use visual cues to manipulate where attention is focused ("cued" vs "uncued"). Human psychophysical studies often also include neutrally cued trials to study how attention naturally varies between points of interest. But the neuronal correlates of this neutral condition are unclear. We measured behavioral performance and neuronal activity in cued, uncued, and neutrally cued blocks of trials. Behavioral performance and neuronal responses during neutral cueing were intermediate to those of the cued and uncued conditions. We found no signatures of a single mechanism of attention that switches between stimulus locations. Thus, attention-related changes in neuronal activity are largely hemisphere-specific and graded according to task demands. Copyright © 2016 the authors 0270-6474/16/365353-09$15.00/0.

Graded Neuronal Modulations Related to Visual Spatial Attention

PubMed Central

Maunsell, John H. R.

2016-01-01

Studies of visual attention in monkeys typically measure neuronal activity when the stimulus event to be detected occurs at a cued location versus when it occurs at an uncued location. But this approach does not address how neuronal activity changes relative to conditions where attention is unconstrained by cueing. Human psychophysical studies have used neutral cueing conditions and found that neutrally cued behavioral performance is generally intermediate to that of cued and uncued conditions (Posner et al., 1978; Mangun and Hillyard, 1990; Montagna et al., 2009). To determine whether the neuronal correlates of visual attention during neutral cueing are similarly intermediate, we trained macaque monkeys to detect changes in stimulus orientation that were more likely to occur at one location (cued) than another (uncued), or were equally likely to occur at either stimulus location (neutral). Consistent with human studies, performance was best when the location was cued, intermediate when both locations were neutrally cued, and worst when the location was uncued. Neuronal modulations in visual area V4 were also graded as a function of cue validity and behavioral performance. By recording from both hemispheres simultaneously, we investigated the possibility of switching attention between stimulus locations during neutral cueing. The results failed to support a unitary “spotlight” of attention. Overall, our findings indicate that attention-related changes in V4 are graded to accommodate task demands. SIGNIFICANCE STATEMENT Studies of the neuronal correlates of attention in monkeys typically use visual cues to manipulate where attention is focused (“cued” vs “uncued”). Human psychophysical studies often also include neutrally cued trials to study how attention naturally varies between points of interest. But the neuronal correlates of this neutral condition are unclear. We measured behavioral performance and neuronal activity in cued, uncued, and neutrally cued blocks of trials. Behavioral performance and neuronal responses during neutral cueing were intermediate to those of the cued and uncued conditions. We found no signatures of a single mechanism of attention that switches between stimulus locations. Thus, attention-related changes in neuronal activity are largely hemisphere-specific and graded according to task demands. PMID:27170131

Enhancement of endotoxin neutralization by coupling of a C12-alkyl chain to a lactoferricin-derived peptide

PubMed Central

2004-01-01

Antibacterial peptide acylation, which mimics the structure of the natural lipopeptide polymyxin B, increases antimicrobial and endotoxin-neutralizing activities. The interaction of the lactoferricin-derived peptide LF11 and its N-terminally acylated analogue, lauryl-LF11, with different chemotypes of bacterial lipopolysaccharide (LPS Re, Ra and smooth S form) was investigated by biophysical means and was related to the peptides' biological activities. Both peptides exhibit high antibacterial activity against the three strains of Salmonella enterica differing in the LPS chemotype. Lauryl-LF11 has one order of magnitude higher activity against Re-type, but activity against Ra- and S-type bacteria is comparable with that of LF11. The alkyl derivative peptide lauryl-LF11 shows a much stronger inhibition of the LPS-induced cytokine induction in human mononuclear cells than LF11. Although peptide–LPS interaction is essentially of electrostatic nature, the lauryl-modified peptide displays a strong hydrophobic component. Such a feature might then explain the fact that saturation of the peptide binding takes place at a much lower peptide/LPS ratio for LF11 than for lauryl-LF11, and that an overcompensation of the negative LPS backbone charges is observed for lauryl-LF11. The influence of LF11 on the gel-to-liquid-crystalline phase-transition of LPS is negligible for LPS Re, but clearly fluidizing for LPS Ra. In contrast, lauryl-LF11 causes a cholesterol-like effect in the two chemotypes, fluidizing in the gel and rigidifying of the hydrocarbon chains in the liquid-crystalline phase. Both peptides convert the mixed unilamellar/non-lamellar aggregate structure of lipid A, the ‘endotoxic principle’ of LPS, into a multilamellar one. These data contribute to the understanding of the mechanisms of the peptide-mediated neutralization of endotoxin and effect of lipid modification of peptides. PMID:15344905

Sodium ions activated phosphofructokinase leading to enhanced D-lactic acid production by Sporolactobacillus inulinus using sodium hydroxide as a neutralizing agent.

PubMed

Zheng, Lu; Liu, Mingqing; Sun, Jiaduo; Wu, Bin; He, Bingfang

2017-05-01

Sporolactobacillus inulinus is a superior D-lactic acid-producing bacterium and proposed species for industrial production. The major pathway for D-lactic acid biosynthesis, glycolysis, is mainly regulated via the two irreversible steps catalyzed by the allosteric enzymes, phosphofructokinase (PFK) and pyruvate kinase. The activity level of PFK was significantly consistent with the cell growth and D-lactic acid production, indicating its vital role in control and regulation of glycolysis. In this study, the ATP-dependent PFK from S. inulinus was expressed in Escherichia coli and purified to homogeneity. The PFK was allosterically activated by both GDP and ADP and inhibited by phosphoenolpyruvate; the addition of activators could partly relieve the inhibition by phosphoenolpyruvate. Furthermore, monovalent cations could enhance the activity, and Na + was the most efficient one. Considering this kind activation, NaOH was investigated as the neutralizer instead of the traditional neutralizer CaCO 3 . In the early growth stage, the significant accelerated glucose consumption was achieved in the NaOH case probably for the enhanced activity of Na + -activated PFK. Using NaOH as the neutralizer at pH 6.5, the fermentation time was greatly shortened about 22 h; simultaneously, the glucose consumption rate and the D-lactic acid productivity were increased by 34 and 17%, respectively. This probably contributed to the increased pH and Na + -promoted activity of PFK. Thus, fermentations by S. inulinus using the NaOH neutralizer provide a green and highly efficient D-lactic acid production with easy subsequent purification.

Lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated.

PubMed

Dumas, Eric K; Garman, Lori; Cuthbertson, Hannah; Charlton, Sue; Hallis, Bassam; Engler, Renata J M; Choudhari, Shyamal; Picking, William D; James, Judith A; Farris, A Darise

2017-06-08

A major difference between two currently licensed anthrax vaccines is presence (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT) component Lethal Factor (LF). The primary immunogen in both vaccine formulations is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrated that LF antibodies can be protective. In this report we compared humoral immune responses in cohorts of AVP (n=39) and AVA recipients (n=78) matched 1:2 for number of vaccinations and time post-vaccination, and evaluated whether the LF response contributes to LT neutralization in human recipients of AVP. PA response rates (≥95%) and PA IgG concentrations were similar in both groups; however, AVP recipients exhibited higher LT neutralization ED 50 values (AVP: 1464.0±214.7, AVA: 544.9±83.2, p<0.0001) and had higher rates of LF IgG positivity (95%) compared to matched AVA vaccinees (1%). Multiple regression analysis revealed that LF IgG makes an independent and additive contribution to the LT neutralization response in the AVP group. Affinity purified LF antibodies from two independent AVP recipients neutralized LT and bound to LF Domain 1, confirming contribution of LF antibodies to LT neutralization. This study documents the benefit of including an LF component to PA-based anthrax vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

A New Neutral-pH Low-GDP Peritoneal Dialysis Fluid

PubMed Central

Himmele, Rainer; Jensen, Lynn; Fenn, Dominik; Ho, Chih-Hu; Sawin, Dixie-Ann; Diaz-Buxo, Jose A.

2012-01-01

♦ Background: Conventional peritoneal dialysis fluids (PDFs) consist of ready-to-use solutions with an acidic pH. Sterilization of these fluids is known to generate high levels of glucose degradation products (GDPs). Although several neutral-pH, low-GDP PD solutions have been developed, none are commercially available in the United States. We analyzed pH and GDPs in Delflex Neutral pH (Fresenius Medical Care North America, Waltham, MA, USA), the first neutral-pH PDF to be approved by the US Food and Drug Administration. ♦ Methods: We evaluated whether patients (n = 26; age range: 18 - 78 years) could properly mix the Delflex Neutral pH PDF after standardized initial training. We further analyzed the concentrations of 10 different glucose degradation products in Delflex Neutral pH PDF and compared the results with similar analyses in other commercially available biocompatible PDFs. ♦ Results: All pH measurements (n = 288) in the delivered Delflex Neutral pH solution consistently fell within the labeled range of 7.0 ± 0.4. Analysis of mixing errors showed no significant impact on the pH results. Delflex Neutral pH, Balance (Fresenius Medical Care, Bad Homburg, Germany), BicaVera (Fresenius Medical Care), and Gambrosol Trio (Gambro Lundia AB, Lund, Sweden) exhibited similar low total GDP concentrations, with maximums in the 4.25% solutions of 88 μmol/L, 74 μmol/L, 74 μmol/L, and 79 μmol/L respectively; the concentration in Physioneal (Baxter Healthcare Corporation, Deerfield, IL, USA) was considerably higher at 263.26 μmol/L. The total GDP concentration in Extraneal (Baxter Healthcare Corporation) was 63 μmol/L, being thus slightly lower than the concentrations in the 4.25% glucose solutions, but higher than the concentrations in the 1.5% and 2.5% glucose solutions. ♦ Conclusions: The new Delflex Neutral pH PDF consistently delivers neutral pH with minimal GDPs. PMID:22383632

8. LESLIE WICKMAN, EVA (EXTRA VEHICULAR ACTIVITIES) SPECIALIST, GETTING OUT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. LESLIE WICKMAN, EVA (EXTRA VEHICULAR ACTIVITIES) SPECIALIST, GETTING OUT OF SPACE SUIT AFTER TESTING IN NEUTRAL BUOYANCY TANK. AVERAGE COST OF SUIT $1,000,000. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

Sex differences in neural responses to disgusting visual stimuli: implications for disgust-related psychiatric disorders.

PubMed

Caseras, Xavier; Mataix-Cols, David; An, Suk Kyoon; Lawrence, Natalia S; Speckens, Anne; Giampietro, Vincent; Brammer, Michael J; Phillips, Mary L

2007-09-01

A majority of patients with disgust-related psychiatric disorders such as animal phobias and contamination-related obsessive-compulsive disorder are women. The aim of this functional magnetic resonance imaging (fMRI) study was to examine possible sex differences in neural responses to disgust-inducing stimuli that might help explain this female predominance. Thirty-four healthy adult volunteers (17 women, all right-handed) were scanned while viewing alternating blocks of disgusting and neutral pictures from the International Affective Picture System. Using a partially-silent fMRI sequence, the participants rated their level of discomfort after each block of pictures. Skin conductance responses (SCR) were measured throughout the experiment. All participants completed the Disgust Scale. Both women and men reported greater subjective discomfort and showed more SCR fluctuations during the disgusting picture blocks than during the neutral picture blocks. Women and men also demonstrated a similar pattern of brain response to disgusting compared with neutral pictures, showing activation in the anterior insula, ventrolateral and dorsolateral prefrontal cortices, and visual regions. Compared with men, women had significantly higher disgust sensitivity scores, experienced more subjective discomfort, and demonstrated greater activity in left ventrolateral prefrontal regions. However, these differences were no longer significant when disgust sensitivity scores were controlled for. In healthy adult volunteers, there are significant sex-related differences in brain responses to disgusting stimuli that are irrevocably linked to greater disgust sensitivity scores in women. The implications for disgust-related psychiatric disorders are discussed.

Stealth properties of poly(ethylene oxide)-based triblock copolymer micelles: a prerequisite for a pH-triggered targeting system.

PubMed

Van Butsele, K; Morille, M; Passirani, C; Legras, P; Benoit, J P; Varshney, S K; Jérôme, R; Jérôme, C

2011-10-01

Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon protonation under acidic conditions, pH-sensitive poly(2-vinylpyridine) (P2VP) blocks were stretched, exhibiting positive charges at the periphery of the micelles as well as being a model targeting unit. The polymer micelles were based on two different macromolecular architectures, an ABC miktoarm star terpolymer and an ABC linear triblock copolymer, which combined three different polymer blocks, i.e. hydrophobic poly(ε-caprolactone), PEO and P2VP. Neutral polymer micelles were formed at physiological pH. These systems were tested for their ability to avoid macrophage uptake, their complement activation and their pharmacological behavior after systemic injection in mice, as a function of their conformation (neutral or protonated). After protonation, complement activation and macrophage uptake were up to twofold higher than for neutral systems. By contrast, when P2VP blocks and the targeting unit were buried by the PEO shell at physiological pH, micelle stealth properties were improved, allowing their future systemic injection with an expected long circulation in blood. Smart systems responsive to pH were thus developed which therefore hold great promise for targeted drug delivery to an acidic tumoral environment. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biologically important compounds in synfuels processes

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

Clark, B R; Ho, C; Griest, W H

1980-01-01

Crude products, by-products and wastes from synfuel processes contain a broad spectrum of chemical compounds - many of which are active in biological systems. Discerning which compound classes are most important is necessary in order to establish effective control over release or exposure. Polycyclic aromatic hydrocarbons (PAH), multialkylated PAH, primary aromatic amines and N-heterocyclic PAH are significant contributors to the overall mutagenic activities of a large number of materials examined. Ames test data show that the basic, primary aromatic amine fraction is the most active. PAHs, multialkylated PAHs and N-heterocyclic PAHs are all components of the neutral fraction. In nearlymore » all cases, the neutral fractions contribute the largest portion of the mutagenic activity, while the basic primary aromatic amine fractions have the highest specific activity. Neutral fractions are usually the largest (wt %) whereas the total basic fractions are small by comparison; thus, the overall greater contribution of the neutral fraction to the mutagenic activity of most samples. Biologically active constituents are isolated in preparative scale amounts from complex mixtures utilizing combinations of liquid-liquid extraction and various liquid chromatographic column-eluant combinations. Fractions are characterized using a combination of spectroscopic techniques and gas chromatography/mass spectrometry.« less

Attachment anxiety benefits from security priming: Evidence from working memory performance

PubMed Central

2018-01-01

The present study investigates the relationship between the attachment dimensions (anxious vs. avoidance) and the cognitive performance of individuals, specifically whether the attachment dimensions would predict the working memory (WM) performance. In the n-back task, reflecting the WM capacity, both attachment related and non-attachment related words were used. Participants were randomly assigned into two groups that received either the secure or the neutral subliminal priming. In the secure priming condition, the aim was to induce sense of security by presenting secure attachment words prior to the n-back task performance. In neutral priming condition, neutral words that did not elicit sense of security were presented. Structural equation modeling revealed divergent patterns for attachment anxiety and avoidance dimensions under the different priming conditions. In neutral priming condition, WM performance declined in terms of capacity in the n-back task for individuals who rated higher levels of attachment anxiety. However in the secure priming condition, WM performance was boosted in the n-back task for individuals who rated higher levels of attachment anxiety. In other words, the subliminal priming of the security led to increased WM capacity of individuals who rated higher levels of attachment anxiety. This effect, however, was not observed for higher levels of attachment avoidance. Results are discussed along the lines of hyperactivation and deactivation strategies of the attachment system. PMID:29522549

Daboia russellii and Naja kaouthia venom neutralization by lupeol acetate isolated from the root extract of Indian sarsaparilla Hemidesmus indicus R.Br.

PubMed

Chatterjee, Ipshita; Chakravarty, A K; Gomes, A

2006-06-15

The present study reports the isolation and purification of lupeol acetate from the methanolic root extract of Indian medicinal plant Hemidesmus indicus (L.) R.Br. (family: Asclepiadaceae) which could neutralize venom induced action of Daboia russellii and Naja kaouthia on experimental animals. Lupeol acetate could significantly neutralize lethality, haemorrhage, defibrinogenation, edema, PLA(2) activity induced by Daboia russellii venom. It also neutralized Naja kaouthia venom induced lethality, cardiotoxicity, neurotoxicity and respiratory changes in experimental animals. Lupeol acetate potentiated the protection by snake venom antiserum action against Daboia russellii venom induced lethality in male albino mice. Venom induced changes in lipid peroxidation and super oxide dismutase activity was antagonized by lupeol acetate. Snake venom neutralization by lupeol acetate and its possible mechanism of action has been discussed.

Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

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

Shedlock, Devon J., E-mail: shedlock@mail.med.upenn.ed; Bailey, Michael A., E-mail: mike.bailey@taurigroup.co; Popernack, Paul M.

2010-06-05

Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished bymore » reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.« less

Neutral particle beam intensity controller

DOEpatents

Dagenhart, William K.

1986-01-01

A neutral beam intensity controller is provided for a neutral beam generator in which a neutral beam is established by accelerating ions from an ion source into a gas neutralizer. An amplitude modulated, rotating magnetic field is applied to the accelerated ion beam in the gas neutralizer to defocus the resultant neutral beam in a controlled manner to achieve intensity control of the neutral beam along the beam axis at constant beam energy. The rotating magnetic field alters the orbits of ions in the gas neutralizer before they are neutralized, thereby controlling the fraction of neutral particles transmitted out of the neutralizer along the central beam axis to a fusion device or the like. The altered path or defocused neutral particles are sprayed onto an actively cooled beam dump disposed perpendicular to the neutral beam axis and having a central open for passage of the focused beam at the central axis of the beamline. Virtually zero therough 100% intensity control is achieved by varying the magnetic field strength without altering the ion source beam intensity or its species yield.

Impact of neutral density fluctuations on gas puff imaging diagnostics

NASA Astrophysics Data System (ADS)

Wersal, C.; Ricci, P.

2017-11-01

A three-dimensional turbulence simulation of the SOL and edge regions of a toroidally limited tokamak is carried out. The simulation couples self-consistently the drift-reduced two-fluid Braginskii equations to a kinetic equation for neutral atoms. A diagnostic neutral gas puff on the low-field side midplane is included and the impact of neutral density fluctuations on D_α light emission investigated. We find that neutral density fluctuations affect the D_α emission. In particular, at a radial distance from the gas puff smaller than the neutral mean free path, neutral density fluctuations are anti-correlated with plasma density, electron temperature, and D_α fluctuations. It follows that the neutral fluctuations reduce the D_α emission in most of the observed region and, therefore, have to be taken into account when interpreting the amplitude of the D_α emission. On the other hand, higher order statistical moments (skewness, kurtosis) and turbulence characteristics (such as correlation length, or the autocorrelation time) are not significantly affected by the neutral fluctuations. At distances from the gas puff larger than the neutral mean free path, a non-local shadowing effect influences the neutral density fluctuations. There, the D_α fluctuations are correlated with the neutral density fluctuations, and the high-order statistical moments and measurements of other turbulence properties are strongly affected by the neutral density fluctuations.

Evaluation of antioxidant activity and electronic structure of aspirin and paracetamol

NASA Astrophysics Data System (ADS)

Motozaki, W.; Nagatani, Y.; Kimura, Y.; Endo, K.; Takemura, T.; Kurmaev, E. Z.; Moewes, A.

2011-01-01

We present a study of electronic structure, chemical bonding, and antioxidant activity of phenolic antioxidants (aspirin and paracetamol). X-ray photoelectron and emission spectra of the antioxidants have been simulated by deMon density functional theory (DFT) calculations of the molecules. The chemical bonding of aspirin is characterized by the formation of oxygen 'lone-pair' π-orbitals which can neutralize free radicals and thus be related to antioxidant properties of the drug. In the case of paracetamol the additional nitrogen 'lone pair' is formed which can explain toxicity of the drug. We propose an evaluation method of antioxidant activity based on the relationship between experimental half-wave oxidation potential ( Ep/2 ) and calculated ionization potentials ( IP) by the DFT calculations, and can conclude that paracetamol has the higher antioxidant activity than aspirin.

The serotonin transporter gene polymorphism and the effect of baseline on amygdala response to emotional faces.

PubMed

von dem Hagen, Elisabeth A H; Passamonti, Luca; Nutland, Sarah; Sambrook, Jennifer; Calder, Andrew J

2011-03-01

Previous research has found that a common polymorphism in the serotonin transporter gene (5-HTTLPR) is an important mediator of individual differences in brain responses associated with emotional behaviour. In particular, relative to individuals homozygous for the l-allele, carriers of the s-allele display heightened amygdala activation to emotional compared to non-emotional stimuli. However, there is some debate as to whether this difference is driven by increased activation to emotional stimuli, resting baseline differences between the groups, or decreased activation to neutral stimuli. We performed functional imaging during an implicit facial expression processing task in which participants viewed angry, sad and neutral faces. In addition to neutral faces, we included two further baseline conditions, houses and fixation. We found increased amygdala activation in s-allele carriers relative to l-homozygotes in response to angry faces compared to neutral faces, houses and fixation. When comparing neutral faces to houses or fixation, we found no significant difference in amygdala response between the two groups. In addition, there was no significant difference between the groups in response to fixation when compared with a houses baseline. Overall, these results suggest that the increased amygdala response observed in s-allele carriers to emotional faces is primarily driven by an increased response to emotional faces rather than a decreased response to neutral faces or an increased resting baseline. The results are discussed in relation to the tonic and phasic hypotheses of 5-HTTLPR-mediated modulation of amygdala activity. Copyright © 2010 Elsevier Ltd. All rights reserved.

pH-dependent biotransformation of ionizable organic micropollutants in activated sludge.

PubMed

Gulde, Rebekka; Helbling, Damian E; Scheidegger, Andreas; Fenner, Kathrin

2014-12-02

Removal of micropollutants (MPs) during activated sludge treatment can mainly be attributed to biotransformation and sorption to sludge flocs, whereby the latter process is known to be of minor importance for polar organic micropollutants. In this work, we investigated the influence of pH on the biotransformation of MPs with cationic-neutral speciation in an activated sludge microbial community. We performed batch biotransformation, sorption control, and abiotic control experiments for 15 MPs with cationic-neutral speciation, one control MP with neutral-anionic speciation, and two neutral MPs at pHs 6, 7, and 8. Biotransformation rate constants corrected for sorption and abiotic processes were estimated from measured concentration time series with Bayesian inference. We found that biotransformation is pH-dependent and correlates qualitatively with the neutral fraction of the ionizable MPs. However, a simple speciation model based on the assumption that only the neutral species is efficiently taken up and biotransformed by the cells tends to overpredict the effect of speciation. Therefore, additional mechanisms such as uptake of the ionic species and other more complex attenutation mechanisms are discussed. Finally, we observed that the sorption coefficients derived from our control experiments were small and showed no notable pH-dependence. From this we conclude that pH-dependent removal of polar, ionizable organic MPs in activated sludge systems is less likely an effect of pH-dependent sorption but rather of pH-dependent biotransformation. The latter has the potential to cause marked differences in the removal of polar, ionizable MPs at different operational pHs during activated sludge treatment.

Preferential amygdala reactivity to the negative assessment of neutral faces.

PubMed

Blasi, Giuseppe; Hariri, Ahmad R; Alce, Guilna; Taurisano, Paolo; Sambataro, Fabio; Das, Saumitra; Bertolino, Alessandro; Weinberger, Daniel R; Mattay, Venkata S

2009-11-01

Prior studies suggest that the amygdala shapes complex behavioral responses to socially ambiguous cues. We explored human amygdala function during explicit behavioral decision making about discrete emotional facial expressions that can represent socially unambiguous and ambiguous cues. During functional magnetic resonance imaging, 43 healthy adults were required to make complex social decisions (i.e., approach or avoid) about either relatively unambiguous (i.e., angry, fearful, happy) or ambiguous (i.e., neutral) facial expressions. Amygdala activation during this task was compared with that elicited by simple, perceptual decisions (sex discrimination) about the identical facial stimuli. Angry and fearful expressions were more frequently judged as avoidable and happy expressions most often as approachable. Neutral expressions were equally judged as avoidable and approachable. Reaction times to neutral expressions were longer than those to angry, fearful, and happy expressions during social judgment only. Imaging data on stimuli judged to be avoided revealed a significant task by emotion interaction in the amygdala. Here, only neutral facial expressions elicited greater activity during social judgment than during sex discrimination. Furthermore, during social judgment only, neutral faces judged to be avoided were associated with greater amygdala activity relative to neutral faces that were judged as approachable. Moreover, functional coupling between the amygdala and both dorsolateral prefrontal (social judgment > sex discrimination) and cingulate (sex discrimination > social judgment) cortices was differentially modulated by task during processing of neutral faces. Our results suggest that increased amygdala reactivity and differential functional coupling with prefrontal circuitries may shape complex decisions and behavioral responses to socially ambiguous cues.

Preferential Amygdala Reactivity to the Negative Assessment of Neutral Faces

PubMed Central

Blasi, Giuseppe; Hariri, Ahmad R.; Alce, Guilna; Taurisano, Paolo; Sambataro, Fabio; Das, Saumitra; Bertolino, Alessandro; Weinberger, Daniel R.; Mattay, Venkata S.

2010-01-01

Background Prior studies suggest that the amygdala shapes complex behavioral responses to socially ambiguous cues. We explored human amygdala function during explicit behavioral decision making about discrete emotional facial expressions that can represent socially unambiguous and ambiguous cues. Methods During functional magnetic resonance imaging, 43 healthy adults were required to make complex social decisions (i.e., approach or avoid) about either relatively unambiguous (i.e., angry, fearful, happy) or ambiguous (i.e., neutral) facial expressions. Amygdala activation during this task was compared with that elicited by simple, perceptual decisions (sex discrimination) about the identical facial stimuli. Results Angry and fearful expressions were more frequently judged as avoidable and happy expressions most often as approachable. Neutral expressions were equally judged as avoidable and approachable. Reaction times to neutral expressions were longer than those to angry, fearful, and happy expressions during social judgment only. Imaging data on stimuli judged to be avoided revealed a significant task by emotion interaction in the amygdala. Here, only neutral facial expressions elicited greater activity during social judgment than during sex discrimination. Furthermore, during social judgment only, neutral faces judged to be avoided were associated with greater amygdala activity relative to neutral faces that were judged as approachable. Moreover, functional coupling between the amygdala and both dorsolateral prefrontal (social judgment > sex discrimination) and cingulate (sex discrimination > social judgment) cortices was differentially modulated by task during processing of neutral faces. Conclusions Our results suggest that increased amygdala reactivity and differential functional coupling with prefrontal circuitries may shape complex decisions and behavioral responses to socially ambiguous cues. PMID:19709644

Dynamic neural activity during stress signals resilient coping

PubMed Central

Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

2016-01-01

Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

Female emotional eaters show abnormalities in consummatory and anticipatory food reward: a functional magnetic resonance imaging study.

PubMed

Bohon, Cara; Stice, Eric; Spoor, Sonja

2009-04-01

To test the hypothesis that emotional eaters show greater neural activation in response to food intake and anticipated food intake than nonemotional eaters and whether these differences are amplified during a negative versus neutral mood state. Female emotional eaters and nonemotional eaters (N = 21) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless control solution while in a negative and neutral mood. Emotional eaters showed greater activation in the parahippocampal gyrus and anterior cingulate (ACC) in response to anticipated receipt of milkshake and greater activation in the pallidum, thalamus, and ACC in response to receipt of milkshake during a negative relative to a neutral mood. In contrast, nonemotional eaters showed decreased activation in reward regions during a negative versus a neutral mood. Results suggest that emotional eating is related to increased anticipatory and consummatory food reward, but only during negative mood. (c) 2008 by Wiley Periodicals, Inc.

A morphological study of waves in the thermosphere using DE-2 observations

NASA Technical Reports Server (NTRS)

Gross, S. H.; Kuo, S. P.; Shmoys, J.

1986-01-01

Theoretical model and data analysis of DE-2 observations for determining the correlation between the neutral wave activity and plasma irregularities have been presented. The relationships between the observed structure of the sources, precipitation and joule heating, and the fluctuations in neutral and plasma parameters are obtained by analyzing two measurements of neutral atmospheric wave activity and plasma irregularities by DE-2 during perigee passes at an altitude on the order of 300 to 350 km over the polar cap. A theoretical model based on thermal nonlinearity (joule heating) to give mode-mode coupling is developed to explore the role of neutral disturbance (winds and gravity waves) on the generation of plasma irregularities.

Effects of pelvic tilt angles and forced vital capacity in healthy individuals

PubMed Central

Hwang, Young-In; Kim, Ki-Song

2018-01-01

[Purpose] The purpose of this study was to investigate the effect of pelvic tilt angles and lung function in participants performing pelvic tilts on a ball. [Subjects and Methods] Eighteen subjects participated in this study. While they performed pelvic tilt on sitting at a ball, the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) were measured at 10 degrees of anterior and posterior pelvic tilt, respectively, and neutral position. The repeated measure ANOVA was performed, and the Bonferroni correction was used for post-hoc analysis. [Results] The PEF of the participants was significantly higher at neutral position, compared with an anterior pelvic tilt at 10 degrees. The FEV1 was also higher in neutral position, compared with anterior and posterior pelvic tilt. [Conclusion] This study underlines the need for the standardization of the FVC testing protocol for positioning the pelvic angle in a neutral position in patients with respiratory disorders to promote reliable interpretation of intervention outcomes. PMID:29410572

Identification of Human Papillomavirus Type 16 L1 Surface Loops Required for Neutralization by Human Sera†

PubMed Central

Carter, Joseph J.; Wipf, Greg C.; Madeleine, Margaret M.; Schwartz, Stephen M.; Koutsky, Laura A.; Galloway, Denise A.

2006-01-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface. PMID:16641259

Identification of human papillomavirus type 16 L1 surface loops required for neutralization by human sera.

PubMed

Carter, Joseph J; Wipf, Greg C; Madeleine, Margaret M; Schwartz, Stephen M; Koutsky, Laura A; Galloway, Denise A

2006-05-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface.

Effect of pulsed electric fields on the activity of neutral trehalase from beer yeast and RSM analysis.

PubMed

Ye, Haiqing; Jin, Yan; Lin, Songyi; Liu, Mingyuan; Yang, Yi; Zhang, Meishuo; Zhao, Ping; Jones, Gregory

2012-06-01

The trehalase activity plays an important role in extraction of trehalose from beer yeast. In this study, the effect of pulsed electric field processing on neutral trehalase activity in beer yeast was investigated. In order to develop and optimize a pulsed electric field (PEF) mathematical model for activating the neutral trehalase, we have investigated three variables, including electric field intensity (10-50 kV/cm), pulse duration (2-10 μs) and liquid-solid ratio (20-50 ml/g) and subsequently optimized them by response surface methodology (RSM). The experimental data were fitted to a second-order polynomial equation and profiled into the corresponding contour plots. Optimal condition obtained by RSM is as follows: electric field intensity 42.13 kV/cm, liquid-solid ratio 30.12 ml/g and pulse duration 5.46 μs. Under these conditions, with the trehalose decreased 8.879 mg/L, the PEF treatment had great effect on activating neutral trehalase in beer yeast cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Visual cortex and cerebellum hyperactivation during negative emotion picture stimuli in migraine patients.

PubMed

Wang, Mengxing; Su, Jingjing; Zhang, Jilei; Zhao, Ying; Yao, Qian; Zhang, Qiting; Zhang, Hui; Wang, Shuo; Li, Ge-Fei; Liu, Jian-Ren; Du, Xiaoxia

2017-02-09

Migraines are a common and undertreated disease and often have psychiatric comorbidities; however, the abnormal mechanism of emotional processing in migraine patients has not been well clarified. This study sought to investigate the different brain functional activation to neutral, positive and negative emotional stimuli between migraine and healthy subjects. Twenty-six adults with migraines and 26 healthy adults, group-matched for sex and age, participated in this experiment. Although there were no significant differences between two groups during the viewing of positive affective pictures vs. neutral affective pictures, there were different activation patterns during the viewing of negative to neutral affective pictures in the two groups; the control group showed both increased and decreased activation patterns, while the migraine subjects showed only increased activation. Negative affective pictures elicited stronger activation than neutral affective pictures in migraineurs, which included the bilateral cerebellum anterior lobe/culmen, the bilateral lingual gyri, the bilateral precuneus and the left cuneus. Our data indicated that migraine patients were hypersensitive to negative stimuli, which might provide clues to aid in the understanding of the pathophysiology and psychiatric comorbidities of migraines.

Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity.

PubMed

Feng, Ying; Sun, Xikui; Ye, Xianmiao; Feng, Yupeng; Wang, Jinlin; Zheng, Xuehua; Liu, Xinglong; Yi, Changhua; Hao, Mingli; Wang, Qian; Li, Feng; Xu, Wei; Li, Liang; Li, Chufang; Zhou, Rong; Chen, Ling; Feng, Liqiang

2018-05-01

Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of sperm DNA quality in men presenting with testicular cancer and lymphoma using alkaline and neutral Comet assays.

PubMed

Kumar, K; Lewis, S; Vinci, S; Riera-Escamilla, A; Fino, M-G; Tamburrino, L; Muratori, M; Larsen, P; Krausz, C

2018-01-01

Despite more cancers in young men over the past two decades, improvements in therapies give a greater chance to live full lives following treatment. Sperm genomic quality is variable following cancer diagnosis, so its assessment is important if sperm cryopreservation is being considered. Here, we evaluated DNA damage using two DNA damage assays: an alkaline and for the first time, a neutral Comet assays in men presenting with testicular cancer (n = 19 for alkaline and 13 for neutral group) and lymphoma (n = 13 for alkaline and 09 for neutral group) compared with fertile donors (n = 20 for alkaline and 14 for neutral group). No significant differences were observed in any semen analysis parameters. In contrast, sperm DNA damage was higher in men with testicular cancer than in donors as assessed by both the alkaline (12.4% vs. 37.4%, p < 0.001) and neutral (7.5% vs. 13.4%; p < 0.05) Comet assays. Similar trends were observed in men with lymphoma. Here, sperm DNA damage was higher using both the alkaline (35.0% vs. 12.4%) and neutral (10.7% against 7.5% (p < 0.05) Comet assays. Moreover, the DNA strand breaks (particularly double-strand breaks) were significantly more prominent in men with cancer having abnormal seminal parameters than normozoospermic ones. This study showed that sperm DNA testing using alkaline and neutral Comet assays is more sensitive than semen analysis in detecting impaired sperm quality in men presenting with cancer. It may provide a useful adjunct when considering storage prior to cancer investigations and assisted reproductive techniques (ART)-based treatment. © 2017 American Society of Andrology and European Academy of Andrology.

Redox-Controlled Olefin (Co)Polymerization Catalyzed by Ferrocene-Bridged Phosphine-Sulfonate Palladium Complexes.

PubMed

Chen, Min; Yang, Bangpei; Chen, Changle

2015-12-14

The facile and reversible interconversion between neutral and oxidized forms of palladium complexes containing ferrocene-bridged phosphine sulfonate ligands was demonstrated. The activity of these palladium complexes could be controlled using redox reagents during ethylene homopolymerization, ethylene/methyl acrylate copolymerization, and norbornene oligomerization. Specifically in norbornene oligomerization, the neutral complexes were not active at all whereas the oxidized counterparts showed appreciable activity. In situ switching between the neutral and oxidized forms resulted in an interesting "off" and "on" behavior in norbornene oligomerization. This work provides a new strategy to control the olefin polymerization process. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solar cycle evolution of solar wind speed structure between 1973 and 1985 observed with the interplanetary scintillation method

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

Kojima, M.; Kakinuma, T.

1987-07-01

The solar cycle evolution of solar wind speed structure was studied for the years from 1973 to 1985 on a basis of interplanetary scintillation observations using a new method for mapping solar wind speed to the source surface. The major minimum-speed regions are distributed along a neutral line through the whole period of a solar cycle: when solar activity is low, they are distributed on the wavy neutral line along the solar equator; in the active phase they also tend to be distributed along the neutral line, which has a large latitudinal amplitude. The minimum-speed regions tend to be distributedmore » not only along the neutral line but also at low magnetic intensity regions and/or coronal bright regions which do not correspond to the neutral line. As the polar high-speed regions extend equatorward around the minimum phase, the latitudinal gradient of speed increases at the boundaries of the low-speed region, and the width of the low-speed region decreases. One or two years before the minimum of solar activity, two localized minimum-speed regions appear on the neutral line, and their locations are longitudinally separated by 180. copyright American Geophysical Union 1987« less

Updating existing emotional memories involves the frontopolar/orbitofrontal cortex in ways that acquiring new emotional memories does not

PubMed Central

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2011-01-01

In life, we must often learn new associations to people, places, or things we already know. The current functional magnetic resonance imaging study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral objects and encoding tasks. This initial learning phase was followed by a memory updating phase, during which participants learned picture-location associations for old pictures (i.e., pictures previously associated with other neutral stimuli) and new pictures (i.e., pictures not seen in the first phase). There was greater frontopolar/ orbitofrontal (OFC) activity when people learned picture-location associations for old negative pictures than for new negative pictures, but frontopolar OFC activity did not significantly differ during learning locations of old versus new neutral pictures. In addition, frontopolar activity was more negatively correlated with the amygdala when participants learned picture-location associations for old negative pictures than for new negative or old neutral pictures. Past studies revealed that the frontopolar OFC allows for updating the affective values of stimuli in reversal learning or extinction of conditioning (e.g., Izquierdo & Murray, 2005); our findings suggest that it plays a more general role in updating associations to emotional stimuli. PMID:21568639

Neural Activation Underlying Cognitive Control in the Context of Neutral and Affectively Charged Pictures in Children

ERIC Educational Resources Information Center

Lamm, Connie; White, Lauren K.; McDermott, Jennifer Martin; Fox, Nathan A.

2012-01-01

The neural correlates of cognitive control for typically developing 9-year-old children were examined using dense-array ERPs and estimates of cortical activation (LORETA) during a go/no-go task with two conditions: a neutral picture condition and an affectively charged picture condition. Activation was estimated for the entire cortex after which…

Functional interplay of top-down attention with affective codes during visual short-term memory maintenance.

PubMed

Kuo, Bo-Cheng; Lin, Szu-Hung; Yeh, Yei-Yu

2018-06-01

Visual short-term memory (VSTM) allows individuals to briefly maintain information over time for guiding behaviours. Because the contents of VSTM can be neutral or emotional, top-down influence in VSTM may vary with the affective codes of maintained representations. Here we investigated the neural mechanisms underlying the functional interplay of top-down attention with affective codes in VSTM using functional magnetic resonance imaging. Participants were instructed to remember both threatening and neutral objects in a cued VSTM task. Retrospective cues (retro-cues) were presented to direct attention to the hemifield of a threatening object (i.e., cue-to-threat) or a neutral object (i.e., cue-to-neutral) during VSTM maintenance. We showed stronger activity in the ventral occipitotemporal cortex and amygdala for attending threatening relative to neutral representations. Using multivoxel pattern analysis, we found better classification performance for cue-to-threat versus cue-to-neutral objects in early visual areas and in the amygdala. Importantly, retro-cues modulated the strength of functional connectivity between the frontoparietal and early visual areas. Activity in the frontoparietal areas became strongly correlated with the activity in V3a-V4 coding the threatening representations instructed to be relevant for the task. Together, these findings provide the first demonstration of top-down modulation of activation patterns in early visual areas and functional connectivity between the frontoparietal network and early visual areas for regulating threatening representations during VSTM maintenance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose

PubMed Central

2014-01-01

Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. PMID:24444350

Streptococcus oligofermentans Inhibits Streptococcus mutans in Biofilms at Both Neutral pH and Cariogenic Conditions.

PubMed

Bao, Xudong; de Soet, Johannes Jacob; Tong, Huichun; Gao, Xuejun; He, Libang; van Loveren, Cor; Deng, Dong Mei

2015-01-01

Homeostasis of oral microbiota can be maintained through microbial interactions. Previous studies showed that Streptococcus oligofermentans, a non-mutans streptococci frequently isolated from caries-free subjects, inhibited the cariogenic Streptococcus mutans by the production of hydrogen peroxide (HP). Since pH is a critical factor in caries formation, we aimed to study the influence of pH on the competition between S. oligofermentans and S. mutans in biofilms. To this end, S. mutans and S. oligofermentans were inoculated alone or mixed at 1:1 ratio in buffered biofilm medium in a 96-well active attachment model. The single- and dual-species biofilms were grown under either constantly neutral pH or pH-cycling conditions. The latter includes two cycles of 8 h neutral pH and 16 h pH 5.5, used to mimic cariogenic condition. The 48 h biofilms were analysed for the viable cell counts, lactate and HP production. The last two measurements were carried out after incubating the 48 h biofilms in buffers supplemented with 1% glucose (pH 7.0) for 4 h. The results showed that S. oligofermentans inhibited the growth of S. mutans in dual-species biofilms under both tested pH conditions. The lactic acid production of dual-species biofilms was significantly lower than that of single-species S. mutans biofilms. Moreover, dual-species and single-species S. oligofermentans biofilms grown under pH-cycling conditions (with a 16 h low pH period) produced a significantly higher amount of HP than those grown under constantly neutral pH. In conclusion, S. oligofermentans inhibited S. mutans in biofilms not only under neutral pH, but also under pH-cycling conditions, likely through HP production. S. oligofermentans may be a compelling probiotic candidate against caries.

The importance of RSV F protein conformation in VLPs in stimulation of neutralizing antibody titers in mice previously infected with RSV

PubMed Central

Cullen, Lori M.; Schmidt, Madelyn R.; Morrison, Trudy G.

2017-01-01

ABSTRACT Respiratory syncytial virus (RSV) is a significant respiratory pathogen but no vaccine is available. RSV infections present 2 major, unique problems. First, humans can experience repeated infections caused by the same virus sero-group indicating that protective memory responses to RSV infection are defective. Second, most people have been infected with RSV by age 5. Immune responses to these infections, while poorly protective, could impact the effectiveness of a vaccine. The goal of this study was to assess the generation of protective immune responses in mice previously infected with RSV by virus-like particle (VLP) vaccine candidates containing a stabilized pre-fusion form of the RSV F protein or a stabilized post-fusion F protein. We report that a single immunization of RSV-experienced animals with a stabilized pre-fusion F protein VLP stimulated high titers of neutralizing antibody while a single injection of a post-fusion F protein VLP or a second RSV infection only weakly stimulated neutralizing antibody titers. These results suggest that prior RSV infection can induce neutralizing antibody memory responses, which can be activated by pre-F protein VLPs but not by post-F protein VLPs or a subsequent infection. Thus the F protein conformation has a major impact on enhancing production of neutralizing antibodies in RSV-experienced animals. Furthermore, although both VLPs contained the same RSV G protein, the pre-F VLP stimulated significantly higher titers of total anti-G protein IgG than the post-F VLP in both naïve and RSV-experienced animals. Thus the F protein conformation also influences anti-G protein responses. PMID:28604155

The importance of RSV F protein conformation in VLPs in stimulation of neutralizing antibody titers in mice previously infected with RSV.

PubMed

Cullen, Lori M; Schmidt, Madelyn R; Morrison, Trudy G

2017-12-02

Respiratory syncytial virus (RSV) is a significant respiratory pathogen but no vaccine is available. RSV infections present 2 major, unique problems. First, humans can experience repeated infections caused by the same virus sero-group indicating that protective memory responses to RSV infection are defective. Second, most people have been infected with RSV by age 5. Immune responses to these infections, while poorly protective, could impact the effectiveness of a vaccine. The goal of this study was to assess the generation of protective immune responses in mice previously infected with RSV by virus-like particle (VLP) vaccine candidates containing a stabilized pre-fusion form of the RSV F protein or a stabilized post-fusion F protein. We report that a single immunization of RSV-experienced animals with a stabilized pre-fusion F protein VLP stimulated high titers of neutralizing antibody while a single injection of a post-fusion F protein VLP or a second RSV infection only weakly stimulated neutralizing antibody titers. These results suggest that prior RSV infection can induce neutralizing antibody memory responses, which can be activated by pre-F protein VLPs but not by post-F protein VLPs or a subsequent infection. Thus the F protein conformation has a major impact on enhancing production of neutralizing antibodies in RSV-experienced animals. Furthermore, although both VLPs contained the same RSV G protein, the pre-F VLP stimulated significantly higher titers of total anti-G protein IgG than the post-F VLP in both naïve and RSV-experienced animals. Thus the F protein conformation also influences anti-G protein responses.

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.

PubMed

Sholukh, Anton M; Byrareddy, Siddappa N; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Lakhashe, Samir K; Rasmussen, Robert A; Watkins, Jennifer D; Vyas, Hemant K; Thorat, Swati; Brandstoetter, Tania; Mukhtar, Muhammad M; Yoon, John K; Novembre, Francis J; Villinger, Francois; Landucci, Gary; Forthal, Donald N; Ratcliffe, Sarah; Tuero, Iskra; Robert-Guroff, Marjorie; Polonis, Victoria R; Bilska, Miroslawa; Montefiori, David C; Johnson, Welkin E; Ertl, Hildegund C; Ruprecht, Ruth M

2014-01-20

A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C'-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.

Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder.

PubMed

Schlumpf, Yolanda R; Nijenhuis, Ellert R S; Chalavi, Sima; Weder, Ekaterina V; Zimmermann, Eva; Luechinger, Roger; La Marca, Roberto; Reinders, A A T Simone; Jäncke, Lutz

2013-01-01

The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as "Emotional Parts" (EP), but mentally avoid these as "Apparently Normal Parts" of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently. Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures. Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially. DID patients have dissociative part-dependent biopsychosocial reactions to masked neutral and angry faces. As EP, they are overactivated, and as ANP underactivated. The findings support TSDP. Major clinical implications are discussed.

Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder☆

PubMed Central

Schlumpf, Yolanda R.; Nijenhuis, Ellert R.S.; Chalavi, Sima; Weder, Ekaterina V.; Zimmermann, Eva; Luechinger, Roger; La Marca, Roberto; Reinders, A.A.T. Simone; Jäncke, Lutz

2013-01-01

Objective The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as “Emotional Parts” (EP), but mentally avoid these as “Apparently Normal Parts” of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently. Methods Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures. Results Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially. Conclusions DID patients have dissociative part-dependent biopsychosocial reactions to masked neutral and angry faces. As EP, they are overactivated, and as ANP underactivated. The findings support TSDP. Major clinical implications are discussed. PMID:24179849

Neutral depletion and the helicon density limit

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

Magee, R. M.; Galante, M. E.; Carr, J. Jr.

2013-12-15

It is straightforward to create fully ionized plasmas with modest rf power in a helicon. It is difficult, however, to create plasmas with density >10{sup 20} m{sup −3}, because neutral depletion leads to a lack of fuel. In order to address this density limit, we present fast (1 MHz), time-resolved measurements of the neutral density at and downstream from the rf antenna in krypton helicon plasmas. At the start of the discharge, the neutral density underneath the antenna is reduced to 1% of its initial value in 15 μs. The ionization rate inferred from these data implies that the electronmore » temperature near the antenna is much higher than the electron temperature measured downstream. Neutral density measurements made downstream from the antenna show much slower depletion, requiring 14 ms to decrease by a factor of 1/e. Furthermore, the downstream depletion appears to be due to neutral pumping rather than ionization.« less

Upper atmosphere differences between northern and southern high latitudes: The role of magnetic field asymmetry

NASA Astrophysics Data System (ADS)

Förster, Matthias; Cnossen, Ingrid

2013-09-01

The nondipolar portions of the Earth's main magnetic field constitute substantial differences between the two hemispheres. Beside the magnetic flux densities and patterns being different in the Northern Hemisphere (NH) and Southern Hemisphere (SH), also the offset between the invariant magnetic and the geographic poles is larger in the SH than in the NH. We investigated the effects of this magnetic field asymmetry on the high-latitude thermosphere and ionosphere using global numerical simulations and compared our results with recent observations. While the effects on the high-latitude plasma convection are small, the consequences for the neutral wind circulation are substantial. The cross-polar neutral wind and ion drift velocities are generally larger in the NH than the SH, and the hemispheric difference shows a semidiurnal variation. The neutral wind vorticity is likewise larger in the NH than in the SH, with the difference probably becoming larger for higher solar activity. In contrast, the spatial variance of the neutral wind is considerably larger in the SH polar region, with the hemispheric difference showing a strong semidiurnal variation. Its phase is similar to the phase of the semidiurnal variation of the hemispheric magnitude differences. Hemispheric differences in ion drift and neutral wind magnitude are most likely caused partly by the larger magnetic flux densities in the near-polar regions of the SH and partly by the larger offset between the invariant and geographic pole in the SH, while differences in spatial variance are probably just caused by the latter. We conclude that the asymmetry of the magnetic field, both in strength and in orientation, establishes substantial hemispheric differences in the neutral wind and plasma drift in the high-latitude upper atmosphere, which can help to explain observed hemispheric differences found with the Cluster/Electron Drift Instrument (EDI) and the Challenging Minisatellite Payload (CHAMP).

Experiences with new neutralization technologies for remediation after ISL mining of uranium in Straz Pod Ralskem

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

Sedlakova, Veronika; Kaspar, Ludvik; Tykal, Tomas

2013-07-01

A big affection of the rock environment and groundwaters occurred during the chemical mining of uranium in the years 1966 to 1996 in the neighbourhood of the town Straz pod Ralskem in the Czech Republic. It is necessary to clean the residual technological solutions (RTS) from the underground. The pH of the solutions in some places is still less than 2 and the concentration of sulphates reaches up to 65 g/l. The remedial activities consist of pumping of the RTS from the ground and reprocessing of the RTS in the surface technologies. The implementation of the new neutralization technologies NDSmore » ML and NDS 10 help us with increasing of the efficiency of the remedial process. The NDS ML technology ('Mother liquor reprocessing station') started its operation in 2009 and it processes the concentrated technological solution from the evaporation station after the alum crystallization (mother liquor) with the concentration of total dissolved solids up to 250 g/l. The principle is the neutralization of the acid solutions with the aid of the lime milk. The suspension is then filtrated in the filter press, the filter cake is deposited in the tailings pond and the filtrate is injected back into the underground rock environment. The NDS 10 technology ('Neutralization and Decontamination Station NDS 10') started its operation in 2012 and it works on the same technological principle as the NDS ML station. The difference is that the NDS 10 station can process higher volume (4.4 m{sup 3}/min) of the RTS with lower concentration of total dissolved solids 20 - 25 g/l. This poster describes the experiences of the state enterprise DIAMO with putting of these two neutralization technologies into operation and with using of the lime milk neutralization in such a large scale. (authors)« less

Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling.

PubMed

Nawrat, Christopher C; Jamison, Christopher R; Slutskyy, Yuriy; MacMillan, David W C; Overman, Larry E

2015-09-09

Alkyl oxalates are new bench-stable alcohol-activating groups for radical generation under visible light photoredox conditions. Using these precursors, the first net redox-neutral coupling of tertiary and secondary alcohols with electron-deficient alkenes is achieved.

[Changes in the EEG spectral power during perception of neutral and emotionally salient words in schizophrenic patients, their relatives and healthy individuals from the general population].

PubMed

Alfimova, M V; Uvarova, L G

2007-01-01

To search for EEG-correlates of emotional processing that might be indicators of genetic predisposition to schizophrenia, changes in EEG spectral power during perception of neutral and emotionally salient words were examined in 36 schizophrenic patients, 50 of their unaffected first-degree relatives, and 47 healthy individuals without any family history of psychoses. In healthy persons, passive listening to neutral words induced minimum changes in cortical rhythmical activity, predominantly in the form of synchronization of slow and fast waves, whereas perception of emotional words was followed by a generalized depression of the alpha and beta1 activity and a locally specific decrease in the power of theta and beta2 frequency bands. The patients and their relatives showed a decrease in the alpha and beta1 activity simultaneously with an increase in the power of delta activity in response to both groups of words. Thus, in the patients and their relatives, reactions to neutral and emotional words were ulterior as a result of augmented reactions to the neutral words. These findings suggest that the EEG changes reflect familial and possibly hereditable abnormal involuntary attention. No prominent decrease in reactivity to emotional stimuli was revealed in schizophrenic families.

Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

PubMed

Cohen, Yehuda Z; Lorenzi, Julio C C; Seaman, Michael S; Nogueira, Lilian; Schoofs, Till; Krassnig, Lisa; Butler, Allison; Millard, Katrina; Fitzsimons, Tomas; Daniell, Xiaoju; Dizon, Juan P; Shimeliovich, Irina; Montefiori, David C; Caskey, Marina; Nussenzweig, Michel C

2018-03-01

Recently discovered broadly neutralizing antibodies (bNAbs) against HIV-1 demonstrate extensive breadth and potency against diverse HIV-1 strains and represent a promising approach for the treatment and prevention of HIV-1 infection. The breadth and potency of these antibodies have primarily been evaluated by using panels of HIV-1 Env-pseudotyped viruses produced in 293T cells expressing molecularly cloned Env proteins. Here we report on the ability of five bNAbs currently in clinical development to neutralize circulating primary HIV-1 isolates derived from peripheral blood mononuclear cells (PBMCs) and compare the results to those obtained with the pseudovirus panels used to characterize the bNAbs. The five bNAbs demonstrated significantly less breadth and potency against clinical isolates produced in PBMCs than against Env-pseudotyped viruses. The magnitude of this difference in neutralizing activity varied, depending on the antibody epitope. Glycan-targeting antibodies showed differences of only 3- to 4-fold, while antibody 10E8, which targets the membrane-proximal external region, showed a nearly 100-fold decrease in activity between published Env-pseudotyped virus panels and PBMC-derived primary isolates. Utilizing clonal PBMC-derived primary isolates and molecular clones, we determined that the observed discrepancy in bNAb performance is due to the increased sensitivity to neutralization exhibited by 293T-produced Env-pseudotyped viruses. We also found that while full-length molecularly cloned viruses produced in 293T cells exhibit greater sensitivity to neutralization than PBMC-derived viruses do, Env-pseudotyped viruses produced in 293T cells generally exhibit even greater sensitivity to neutralization. As the clinical development of bNAbs progresses, it will be critical to determine the relevance of each of these in vitro neutralization assays to in vivo antibody performance. IMPORTANCE Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Antibodies with exceptional neutralizing activity against HIV-1 may provide several advantages to traditional HIV drugs, including an improved side-effect profile, a reduced dosing frequency, and immune enhancement. The activity of these antibodies has been established in vitro by utilizing HIV-1 Env-pseudotyped viruses derived from circulating viruses but produced in 293T cells by pairing Env proteins with a backbone vector. We tested PBMC-produced circulating viruses against five anti-HIV-1 antibodies currently in clinical development. We found that the activity of these antibodies against PBMC isolates is significantly less than that against 293T Env-pseudotyped viruses. This decline varied among the antibodies tested, with some demonstrating moderate reductions in activity and others showing an almost 100-fold reduction. As the development of these antibodies progresses, it will be critical to determine how the results of different in vitro tests correspond to performance in the clinic. Copyright © 2018 Cohen et al.

A New Understanding of the Europa Atmosphere and Limits on Geophysical Activity

NASA Astrophysics Data System (ADS)

Shemansky, D. E.; Yung, Y. L.; Liu, X.; Yoshii, J.; Hansen, C. J.; Hendrix, A. R.; Esposito, L. W.

2014-12-01

Deep extreme ultraviolet spectrograph exposures of the plasma sheet at the orbit of Europa, obtained in 2001 using the Cassini Ultraviolet Imaging Spectrograph experiment, have been analyzed to determine the state of the gas. The results are in basic agreement with earlier results, in particular with Voyager encounter measurements of electron density and temperature. Mass loading rates and lack of detectable neutrals in the plasma sheet, however, are in conflict with earlier determinations of atmospheric composition and density at Europa. A substantial fraction of the plasma species at the Europa orbit are long-lived sulfur ions originating at Io, with ~25% derived from Europa. During the outward radial diffusion process to the Europa orbit, heat deposition forces a significant rise in plasma electron temperature and latitudinal size accompanied with conversion to higher order ions, a clear indication that mass loading from Europa is very low. Analysis of far ultraviolet spectra from exposures on Europa leads to the conclusion that earlier reported atmospheric measurements have been misinterpreted. The results in the present work are also in conflict with a report that energetic neutral particles imaged by the Cassini ion and neutral camera experiment originate at the Europa orbit. An interpretation of persistent energetic proton pitch angle distributions near the Europa orbit as an effect of a significant population of neutral gas is also in conflict with the results of the present work. The general conclusion drawn here is that Europa is geophysically far less active than inferred in previous research, with mass loading of the plasma sheet <=4.5 × 1025 atoms s-1 two orders of magnitude below earlier published calculations. Temporal variability in the region joining the Io and Europa orbits, based on the accumulated evidence, is forced by the response of the system to geophysical activity at Io. No evidence for the direct injection of H2O into the Europa atmosphere or from Europa into the magnetosphere system, as has been observed at Enceladus in the Saturn system, is obtained in the present investigation.

Acid base activity of live bacteria: Implications for quantifying cell wall charge

NASA Astrophysics Data System (ADS)

Claessens, Jacqueline; van Lith, Yvonne; Laverman, Anniet M.; Van Cappellen, Philippe

2006-01-01

To distinguish the buffering capacity associated with functional groups in the cell wall from that resulting from metabolic processes, base or acid consumption by live and dead cells of the Gram-negative bacterium Shewanella putrefaciens was measured in a pH stat system. Live cells exhibited fast consumption of acid (pH 4) or base (pH 7, 8, 9, and 10) during the first few minutes of the experiments. At pH 5.5, no acid or base was required to maintain the initial pH constant. The initial amounts of acid or base consumed by the live cells at pH 4, 8, and 10 were of comparable magnitudes as those neutralized at the same pHs by intact cells killed by exposure to gamma radiation or ethanol. Cells disrupted in a French press required higher amounts of acid or base, due to additional buffering by intracellular constituents. At pH 4, acid neutralization by suspensions of live cells stopped after 50 min, because of loss of viability. In contrast, under neutral and alkaline conditions, base consumption continued for the entire duration of the experiments (5 h). This long-term base neutralization was, at least partly, due to active respiration by the cells, as indicated by the build-up of succinate in solution. Qualitatively, the acid-base activity of live cells of the Gram-positive bacterium Bacillus subtilis resembled that of S. putrefaciens. The pH-dependent charging of ionizable functional groups in the cell walls of the live bacteria was estimated from the initial amounts of acid or base consumed in the pH stat experiments. From pH 4 to 10, the cell wall charge increased from near-zero values to about -4 × 10 -16 mol cell -1 and -6.5 × 10 -16 mol cell -1 for S. putrefaciens and B. subtilis, respectively. The similar cell wall charging of the two bacterial strains is consistent with the inferred low contribution of lipopolysaccharides to the buffering capacity of the Gram-negative cell wall (of the order of 10%).

A NEW UNDERSTANDING OF THE EUROPA ATMOSPHERE AND LIMITS ON GEOPHYSICAL ACTIVITY

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

Shemansky, D. E.; Liu, X.; Yoshii, J.

2014-12-20

Deep extreme ultraviolet spectrograph exposures of the plasma sheet at the orbit of Europa, obtained in 2001 using the Cassini Ultraviolet Imaging Spectrograph experiment, have been analyzed to determine the state of the gas. The results are in basic agreement with earlier results, in particular with Voyager encounter measurements of electron density and temperature. Mass loading rates and lack of detectable neutrals in the plasma sheet, however, are in conflict with earlier determinations of atmospheric composition and density at Europa. A substantial fraction of the plasma species at the Europa orbit are long-lived sulfur ions originating at Io, with ∼25%more » derived from Europa. During the outward radial diffusion process to the Europa orbit, heat deposition forces a significant rise in plasma electron temperature and latitudinal size accompanied with conversion to higher order ions, a clear indication that mass loading from Europa is very low. Analysis of far ultraviolet spectra from exposures on Europa leads to the conclusion that earlier reported atmospheric measurements have been misinterpreted. The results in the present work are also in conflict with a report that energetic neutral particles imaged by the Cassini ion and neutral camera experiment originate at the Europa orbit. An interpretation of persistent energetic proton pitch angle distributions near the Europa orbit as an effect of a significant population of neutral gas is also in conflict with the results of the present work. The general conclusion drawn here is that Europa is geophysically far less active than inferred in previous research, with mass loading of the plasma sheet ≤4.5 × 10{sup 25} atoms s{sup –1} two orders of magnitude below earlier published calculations. Temporal variability in the region joining the Io and Europa orbits, based on the accumulated evidence, is forced by the response of the system to geophysical activity at Io. No evidence for the direct injection of H{sub 2}O into the Europa atmosphere or from Europa into the magnetosphere system, as has been observed at Enceladus in the Saturn system, is obtained in the present investigation.« less

Seroimmunity to polioviruses in U.S. Army recruits.

PubMed

Burke, D S; Gaydos, J C; Hodder, R A; Bancroft, W H

1979-02-01

Titers of neutralizing antibody to poliovirus types 1, 2, and 3 were determined for serum specimens obtained from 268 U.S. Army recruits. Among those tested, 20.9% lacked neutralizing antibody to one or more types of poliovirus, and 1.1% lacked antibody to all three types. An analysis of demographic data showed that age of less than 18 years, schooling for less than 10 years, and residence in the northeastern United States were associated with higher percentages of recruits lacking neutralizing antibodies to polioviruses in serum.

Antigenic Properties of the HIV Envelope on Virions in Solution

PubMed Central

Mengistu, Meron; Lewis, George K.; Lakowicz, Joseph R.

2014-01-01

The structural flexibility found in human immunodeficiency virus (HIV) envelope glycoproteins creates a complex relationship between antigenicity and sensitivity to antiviral antibodies. The study of this issue in the context of viral particles is particularly problematic as conventional virus capture approaches can perturb antigenicity profiles. Here, we employed a unique analytical system based on fluorescence correlation spectroscopy (FCS), which measures antibody-virion binding with all reactants continuously in solution. Panels of nine anti-envelope monoclonal antibodies (MAbs) and five virus types were used to connect antibody binding profiles with neutralizing activities. Anti-gp120 MAbs against the 2G12 or b12 epitope, which marks functional envelope structures, neutralized viruses expressing CCR5-tropic envelopes and exhibited efficient virion binding in solution. MAbs against CD4-induced (CD4i) epitopes considered hidden on functional envelope structures poorly bound these viruses and were not neutralizing. Anti-gp41 MAb 2F5 was neutralizing despite limited virion binding. Similar antigenicity patterns occurred on CXCR4-tropic viruses, except that anti-CD4i MAbs 17b and 19e were neutralizing despite little or no virion binding. Notably, anti-gp120 MAb PG9 and anti-gp41 MAb F240 bound to both CCR5-tropic and CXCR4-tropic viruses without exerting neutralizing activity. Differences in the virus production system altered the binding efficiencies of some antibodies but did not enhance antigenicity of aberrant gp120 structures. Of all viruses tested, only JRFL pseudoviruses showed a direct relationship between MAb binding efficiency and neutralizing potency. Collectively, these data indicate that the antigenic profiles of free HIV particles generally favor the exposure of functional over aberrant gp120 structures. However, the efficiency of virion-antibody interactions in solution inconsistently predicts neutralizing activity in vitro. PMID:24284318

High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis

PubMed Central

Weiss, Eric R.; Alter, Galit; Ogembo, Javier Gordon; Henderson, Jennifer L.; Tabak, Barbara; Bakiş, Yasin; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa

2016-01-01

ABSTRACT The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM. IMPORTANCE Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a major target for antibodies. We report the detection of EBV gp350-specific antibodies capable of neutralizing EBV infection in vitro. The majority of gp350-directed vaccines focus on glycoproteins from lab-adapted strains, which may poorly reflect primary viral envelope diversity. We report some of the first primary gp350 sequences, noting that the gp350 host receptor binding site is remarkably stable across patients and time. However, changes in overall gene diversity were detectable during infection. Patients with higher peripheral blood viral loads in primary infection and greater changes in viral diversity generated more efficient antibodies. Our findings provide insight into the generation of functional antibodies, necessary for vaccine development. PMID:27733645

High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis.

PubMed

Weiss, Eric R; Alter, Galit; Ogembo, Javier Gordon; Henderson, Jennifer L; Tabak, Barbara; Bakiş, Yasin; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Luzuriaga, Katherine

2017-01-01

The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM. Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a major target for antibodies. We report the detection of EBV gp350-specific antibodies capable of neutralizing EBV infection in vitro The majority of gp350-directed vaccines focus on glycoproteins from lab-adapted strains, which may poorly reflect primary viral envelope diversity. We report some of the first primary gp350 sequences, noting that the gp350 host receptor binding site is remarkably stable across patients and time. However, changes in overall gene diversity were detectable during infection. Patients with higher peripheral blood viral loads in primary infection and greater changes in viral diversity generated more efficient antibodies. Our findings provide insight into the generation of functional antibodies, necessary for vaccine development. Copyright © 2016 American Society for Microbiology.

Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera.

PubMed

Ngwuta, Joan O; Chen, Man; Modjarrad, Kayvon; Joyce, M Gordon; Kanekiyo, Masaru; Kumar, Azad; Yassine, Hadi M; Moin, Syed M; Killikelly, April M; Chuang, Gwo-Yu; Druz, Aliaksandr; Georgiev, Ivelin S; Rundlet, Emily J; Sastry, Mallika; Stewart-Jones, Guillaume B E; Yang, Yongping; Zhang, Baoshan; Nason, Martha C; Capella, Cristina; Peeples, Mark E; Ledgerwood, Julie E; McLellan, Jason S; Kwong, Peter D; Graham, Barney S

2015-10-14

Respiratory syncytial virus (RSV) is estimated to claim more lives among infants <1 year old than any other single pathogen, except malaria, and poses a substantial global health burden. Viral entry is mediated by a type I fusion glycoprotein (F) that transitions from a metastable prefusion (pre-F) to a stable postfusion (post-F) trimer. A highly neutralization-sensitive epitope, antigenic site Ø, is found only on pre-F. We determined what fraction of neutralizing (NT) activity in human sera is dependent on antibodies specific for antigenic site Ø or other antigenic sites on F in healthy subjects from ages 7 to 93 years. Adsorption of individual sera with stabilized pre-F protein removed >90% of NT activity and depleted binding antibodies to both F conformations. In contrast, adsorption with post-F removed ~30% of NT activity, and binding antibodies to pre-F were retained. These findings were consistent across all age groups. Protein competition neutralization assays with pre-F mutants in which sites Ø or II were altered to knock out binding of antibodies to the corresponding sites showed that these sites accounted for ~35 and <10% of NT activity, respectively. Binding competition assays with monoclonal antibodies (mAbs) indicated that the amount of site Ø-specific antibodies correlated with NT activity, whereas the magnitude of binding competed by site II mAbs did not correlate with neutralization. Our results indicate that RSV NT activity in human sera is primarily derived from pre-F-specific antibodies, and therefore, inducing or boosting NT activity by vaccination will be facilitated by using pre-F antigens that preserve site Ø. Copyright © 2015, American Association for the Advancement of Science.

Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors.

PubMed

Gray, Elin S; Taylor, Natasha; Wycuff, Diane; Moore, Penny L; Tomaras, Georgia D; Wibmer, Constantinos Kurt; Puren, Adrian; DeCamp, Allan; Gilbert, Peter B; Wood, Blake; Montefiori, David C; Binley, James M; Shaw, George M; Haynes, Barton F; Mascola, John R; Morris, Lynn

2009-09-01

Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon.

Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors▿ †

PubMed Central

Gray, Elin S.; Taylor, Natasha; Wycuff, Diane; Moore, Penny L.; Tomaras, Georgia D.; Wibmer, Constantinos Kurt; Puren, Adrian; DeCamp, Allan; Gilbert, Peter B.; Wood, Blake; Montefiori, David C.; Binley, James M.; Shaw, George M.; Haynes, Barton F.; Mascola, John R.; Morris, Lynn

2009-01-01

Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon. PMID:19553335

Structural Insight into and Mutational Analysis of Family 11 Xylanases: Implications for Mechanisms of Higher pH Catalytic Adaptation.

PubMed

Bai, Wenqin; Zhou, Cheng; Zhao, Yueju; Wang, Qinhong; Ma, Yanhe

2015-01-01

To understand the molecular basis of higher pH catalytic adaptation of family 11 xylanases, we compared the structures of alkaline, neutral, and acidic active xylanases and analyzed mutants of xylanase Xyn11A-LC from alkalophilic Bacillus sp. SN5. It was revealed that alkaline active xylanases have increased charged residue content, an increased ratio of negatively to positively charged residues, and decreased Ser, Thr, and Tyr residue content relative to non-alkaline active counterparts. Between strands β6 and β7, alkaline xylanases substitute an α-helix for a coil or turn found in their non-alkaline counterparts. Compared with non-alkaline xylanases, alkaline active enzymes have an inserted stretch of seven amino acids rich in charged residues, which may be beneficial for xylanase function in alkaline conditions. Positively charged residues on the molecular surface and ionic bonds may play important roles in higher pH catalytic adaptation of family 11 xylanases. By structure comparison, sequence alignment and mutational analysis, six amino acids (Glu16, Trp18, Asn44, Leu46, Arg48, and Ser187, numbering based on Xyn11A-LC) adjacent to the acid/base catalyst were found to be responsible for xylanase function in higher pH conditions. Our results will contribute to understanding the molecular mechanisms of higher pH catalytic adaptation in family 11 xylanases and engineering xylanases to suit industrial applications.

Structural Insight into and Mutational Analysis of Family 11 Xylanases: Implications for Mechanisms of Higher pH Catalytic Adaptation

PubMed Central

Bai, Wenqin; Zhou, Cheng; Zhao, Yueju; Wang, Qinhong; Ma, Yanhe

2015-01-01

To understand the molecular basis of higher pH catalytic adaptation of family 11 xylanases, we compared the structures of alkaline, neutral, and acidic active xylanases and analyzed mutants of xylanase Xyn11A-LC from alkalophilic Bacillus sp. SN5. It was revealed that alkaline active xylanases have increased charged residue content, an increased ratio of negatively to positively charged residues, and decreased Ser, Thr, and Tyr residue content relative to non-alkaline active counterparts. Between strands β6 and β7, alkaline xylanases substitute an α-helix for a coil or turn found in their non-alkaline counterparts. Compared with non-alkaline xylanases, alkaline active enzymes have an inserted stretch of seven amino acids rich in charged residues, which may be beneficial for xylanase function in alkaline conditions. Positively charged residues on the molecular surface and ionic bonds may play important roles in higher pH catalytic adaptation of family 11 xylanases. By structure comparison, sequence alignment and mutational analysis, six amino acids (Glu16, Trp18, Asn44, Leu46, Arg48, and Ser187, numbering based on Xyn11A-LC) adjacent to the acid/base catalyst were found to be responsible for xylanase function in higher pH conditions. Our results will contribute to understanding the molecular mechanisms of higher pH catalytic adaptation in family 11 xylanases and engineering xylanases to suit industrial applications. PMID:26161643

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

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

Zhang, Xinsheng, E-mail: xzhang@iavi.org; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY; Wallace, Olivia L.

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions,more » which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.« less

In vitro activity of a polyhexanide-betaine solution against high-risk clones of multidrug-resistant nosocomial pathogens.

PubMed

López-Rojas, Rafael; Fernández-Cuenca, Felipe; Serrano-Rocha, Lara; Pascual, Álvaro

2017-01-01

To determine the in vitro activity of a polyhexanide-betaine solution against collection strains and multidrug-resistant (MDR) nosocomial isolates, including high-risk clones. We studied of 8 ATCC and 21 MDR clinical strains of Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, including the multiresistant high-risk clones. The MICs and MBCs of a 0.1% polyhexanide-0.1% betaine solution were determined by microdilution. For each species, strains with the highest MICs were selected for further experiments. The dilution-neutralization test (PrEN 12054) was performed by incubating bacterial inocula of 10 6 CFU/mL for 1min with undiluted 0.1% polyhexanide-betaine solution. The CFUs were counted after neutralization. Growth curves and time-kill curves at concentrations of 0.25, 1, 4, and 8×MIC, were performed. MICs of recovered strains were determined when regrowth was observed in time-kill studies after 24h of incubation. Strains with reduced susceptibility were selected by serial passage on plates with increasing concentrations of polyhexanide-betaine, and MICs were determined. Polyhexanide-betaine MIC range was 0.5-8mg/L. MBCs equalled or were 1 dilution higher than MICs. The dilution-neutralization method showed total inoculum clearance of all strains. In time-kill curves, no regrowth was observed at 4×MIC, except for S. aureus (8×MIC). Increased MICs were not observed in time-kill curves, or after serial passages after exposure to polyhexanide-betaine. Polyhexanide-betaine presented bactericidal activity against all MDR clinical isolates tested, including high-risk clones, at significantly lower concentrations and time of activity than those commercially used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Structure-function analysis of Avian β-defensin-6 and β-defensin-12: role of charge and disulfide bridges.

PubMed

Yang, Ming; Zhang, Chunye; Zhang, Xuehan; Zhang, Michael Z; Rottinghaus, George E; Zhang, Shuping

2016-09-09

Avian beta-defensins (AvBD) are small, cationic, antimicrobial peptides. The potential application of AvBDs as alternatives to antibiotics has been the subject of interest. However, the mechanisms of action remain to be fully understood. The present study characterized the structure-function relationship of AvBD-6 and AvBD-12, two peptides with different net positive charges, similar hydrophobicity and distinct tissue expression profiles. AvBD-6 was more potent than AvBD-12 against E. coli, S. Typhimurium, and S. aureus as well as clinical isolates of extended spectrum beta lactamase (ESBL)-positive E. coli and K. pneumoniae. AvBD-6 was more effective than AvBD-12 in neutralizing LPS and interacting with bacterial genomic DNA. Increasing bacterial concentration from 10(5) CFU/ml to 10(9) CFU/ml abolished AvBDs' antimicrobial activity. Increasing NaCl concentration significantly inhibited AvBDs' antimicrobial activity, but not the LPS-neutralizing function. Both AvBDs were mildly chemotactic for chicken macrophages and strongly chemotactic for CHO-K1 cells expressing chicken chemokine receptor 2 (CCR2). AvBD-12 at higher concentrations also induced chemotactic migration of murine immature dendritic cells (DCs). Disruption of disulfide bridges abolished AvBDs' chemotactic activity. Neither AvBDs was toxic to CHO-K1, macrophages, or DCs. AvBDs are potent antimicrobial peptides under low-salt conditions, effective LPS-neutralizing agents, and broad-spectrum chemoattractant peptides. Their antimicrobial activity is positively correlated with the peptides' net positive charges, inversely correlated with NaCl concentration and bacterial concentration, and minimally dependent on intramolecular disulfide bridges. In contrast, their chemotactic property requires the presence of intramolecular disulfide bridges. Data from the present study provide a theoretical basis for the design of AvBD-based therapeutic and immunomodulatory agents.

Effects of worry on physiological and subjective reactivity to emotional stimuli in generalized anxiety disorder and nonanxious control participants.

PubMed

Llera, Sandra J; Newman, Michelle G

2010-10-01

The present study examined the effect of worry versus relaxation and neutral thought activity on both physiological and subjective responding to positive and negative emotional stimuli. Thirty-eight participants with generalized anxiety disorder (GAD) and 35 nonanxious control participants were randomly assigned to engage in worry, relaxation, or neutral inductions prior to sequential exposure to each of four emotion-inducing film clips. The clips were designed to elicit fear, sadness, happiness, and calm emotions. Self reported negative and positive affect was assessed following each induction and exposure, and vagal activity was measured throughout. Results indicate that worry (vs. relaxation) led to reduced vagal tone for the GAD group, as well as higher negative affect levels for both groups. Additionally, prior worry resulted in less physiological and subjective responding to the fearful film clip, and reduced negative affect in response to the sad clip. This suggests that worry may facilitate avoidance of processing negative emotions by way of preventing a negative emotional contrast. Implications for the role of worry in emotion avoidance are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Patients with schizophrenia activate behavioural intentions facilitated by counterfactual reasoning.

PubMed

Contreras, Fernando; Albacete, Auria; Tebé, Cristian; Benejam, Bessy; Caño, Agnes; Menchón, José Manuel

2017-01-01

The main variables assessed were: answer to complete a target task (wrong or correctly), and percentage gain in the reaction time (RT) to complete a target task correctly depending on whether the prime was a counterfactual or a neutral-control cue. These variables were assessed in 37 patients with schizophrenia and 37 healthy controls. Potential associations with clinical status and socio-demographic characteristics were also explored. When a counterfactual prime was presented, the probability of giving an incorrect answer was lower for the entire sample than when a neutral prime was presented (OR 0.58; CI 95% 0.42 to 0.79), but the schizophrenia patients showed a higher probability than the controls of giving an incorrect answer (OR 3.89; CI 95% 2.0 to 7.6). Both the schizophrenia patients and the controls showed a similar percentage gain in RT to a correct answer of 8%. Challenging the results of previous research, our findings suggest a normal activation of behavioural intentions facilitated by CFT in schizophrenia. Nevertheless, the patients showed more difficulty than the controls with the task, adding support to the concept of CFT as a potential new target for consideration in future therapeutic approaches for this illness.

Comparison of Brain Activity Correlating with Self-Report versus Narrative Attachment Measures during Conscious Appraisal of an Attachment Figure

PubMed Central

Yaseen, Zimri S.; Zhang, Xian; Muran, J. Christopher; Winston, Arnold; Galynker, Igor I.

2016-01-01

Objectives: The Adult Attachment Interview (AAI) has been the gold standard of attachment assessment, but requires special training. The Relationship Scales Questionnaire (RSQ) is a widely used self-report measure. We investigate how each correlates with brain activity during appraisal of subjects’ mothers. Methods: Twenty-eight women were scored on the AAI, RSQ, and mood measures. During functional magnetic resonance imaging, subjects viewed their mothers in neutral-, valence-, and salience-rating conditions. We identified regions where contrasts in brain activity between appraisal and neutral viewing conditions correlated with each measure of attachment after covarying for mood. AAI and RSQ measures were then compared in terms of the extent to which regions of correlating brain activity overlapped with “default mode network” (DMN) vs. executive frontal network (EFN) masks and cortical vs. subcortical masks. Additionally, interactions with mood were examined. Results: Salience and valence processing associated with increased thalamo-striatal, posterior cingulate, and visual cortex activity. Salience processing decreased PFC activity, whereas valence processing increased left insula activity. Activity correlating with AAI vs. RSQ measures demonstrated significantly more DMN and subcortical involvement. Interactions with mood were observed in the middle temporal gyrus and precuneus for both measures. Conclusion: The AAI appears to disproportionately correlate with conscious appraisal associated activity in DMN and subcortical structures, while the RSQ appears to tap EFN structures more extensively. Thus, the AAI may assess more interoceptive, ‘core-self’-related processes, while the RSQ captures higher-order cognitions involved in attachment. Shared interaction effects between mood and AAI and RSQ-measures may suggest that processes tapped by each belong to a common system. PMID:27014022

Comparison of Brain Activity Correlating with Self-Report versus Narrative Attachment Measures during Conscious Appraisal of an Attachment Figure.

PubMed

Yaseen, Zimri S; Zhang, Xian; Muran, J Christopher; Winston, Arnold; Galynker, Igor I

2016-01-01

The Adult Attachment Interview (AAI) has been the gold standard of attachment assessment, but requires special training. The Relationship Scales Questionnaire (RSQ) is a widely used self-report measure. We investigate how each correlates with brain activity during appraisal of subjects' mothers. Twenty-eight women were scored on the AAI, RSQ, and mood measures. During functional magnetic resonance imaging, subjects viewed their mothers in neutral-, valence-, and salience-rating conditions. We identified regions where contrasts in brain activity between appraisal and neutral viewing conditions correlated with each measure of attachment after covarying for mood. AAI and RSQ measures were then compared in terms of the extent to which regions of correlating brain activity overlapped with "default mode network" (DMN) vs. executive frontal network (EFN) masks and cortical vs. subcortical masks. Additionally, interactions with mood were examined. Salience and valence processing associated with increased thalamo-striatal, posterior cingulate, and visual cortex activity. Salience processing decreased PFC activity, whereas valence processing increased left insula activity. Activity correlating with AAI vs. RSQ measures demonstrated significantly more DMN and subcortical involvement. Interactions with mood were observed in the middle temporal gyrus and precuneus for both measures. The AAI appears to disproportionately correlate with conscious appraisal associated activity in DMN and subcortical structures, while the RSQ appears to tap EFN structures more extensively. Thus, the AAI may assess more interoceptive, 'core-self'-related processes, while the RSQ captures higher-order cognitions involved in attachment. Shared interaction effects between mood and AAI and RSQ-measures may suggest that processes tapped by each belong to a common system.

Evidence that inhibitory factor extracted from bovine retractor penis is nitrite, whose acid-activated derivative is stabilized nitric oxide.

PubMed Central

Martin, W.; Smith, J. A.; Lewis, M. J.; Henderson, A. H.

1988-01-01

1. Unactivated extracts of bovine retractor penis (BRP) contains 3-7 microM nitrite. Acid-activation of these extracts at pH 2 for 10 min followed by neutralization generates the active form of inhibitory factor (IF; assayed by its vasodilator action on rabbit aorta), and is associated with partial loss of nitrite. 2. Increasing the time of acid-activation at pH 2 from 10 to 60 min with intermittent vortex mixing generates greater vasodilator activity and increases nitrite loss. 3. When acid-activated and neutralized extracts are incubated at 37 degrees C or 30 min or boiled for 5 min, vasodilator activity is lost and nitrite content increased. Reactivation of these samples at pH 2 for 10 min followed by neutralization leads to partial recoveries of vasodilator activity with loss in nitrite content. 4. Addition of sodium nitrite to BRP extracts increases acid-activatable vasodilator activity pro rata. 5. Acid-activation of aqueous sodium nitrite solutions results in less loss of nitrite and generation of less vasodilator activity than BRP extracts. Vasodilatation is only transient and is rapidly abolished on neutralization, whereas responses to acid-activated BRP extracts are more prolonged and activity is stable on ice. 6. Bovine aortic endothelial cells yield vasodilator activity that is indistinguishable from that isolated from BRP. It is activated by acid, stable on ice, abolished by boiling or by haemoglobin, and appears to be due to the generation of nitric oxide (NO) from nitrite.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2897219

The Influence of Different Social Roles Activation on Women's Financial and Consumer Choices.

PubMed

Sekścińska, Katarzyna; Trzcińska, Agata; Maison, Dominika A

2016-01-01

In recent times, the changes occurring in the social role of women and men have been observed. Traditionally, the dominating social role of the woman was as housewife, and that of the man was focused on work and family maintenance. Nowadays, the social role of women is evolving in the direction of taking a profession, while increasingly men are taking care of the household. The main goal of the studies presented here was to verify how the activation of different social roles (traditional or non-traditional) may be reflected in women's financial and consumer choices. Three experimental studies were conducted. In the first study (n = 195 females), three different social roles of women - professional (non-traditional), housewife (traditional) and neutral (control) - were activated. The results showed that activating women's non-traditional social role increased their tendency to invest and decreased their propensity to save money compared to the activation of the traditional or neutral social role. The goal of the second study (n = 196 females) was to check whether, despite there being no differences in the level of consumption in the first study, can any differences be observed in the preference for the type of products chosen for consumption. The results showed that activating the non-traditional social role raised the propensity to spend funds on products and services for individual use and reduced the willingness to buy goods for collective use (shared with other members of the household). The purpose of the third study (n = 90 females) was to examine how different images of women appearing in advertisements may affect women's judgments of the advertised product. Women who watched the ad with woman in the non-traditional social role estimated the product quality, look, color and price higher that participants exposed to the advertisement presenting the woman in traditional or neutral social role. The present studies give some evidence that the new, non-traditional social role of women that is often presented in the media may affect women's everyday financial choices and judgments of products.

The Influence of Different Social Roles Activation on Women’s Financial and Consumer Choices

PubMed Central

Sekścińska, Katarzyna; Trzcińska, Agata; Maison, Dominika A.

2016-01-01

In recent times, the changes occurring in the social role of women and men have been observed. Traditionally, the dominating social role of the woman was as housewife, and that of the man was focused on work and family maintenance. Nowadays, the social role of women is evolving in the direction of taking a profession, while increasingly men are taking care of the household. The main goal of the studies presented here was to verify how the activation of different social roles (traditional or non-traditional) may be reflected in women’s financial and consumer choices. Three experimental studies were conducted. In the first study (n = 195 females), three different social roles of women – professional (non-traditional), housewife (traditional) and neutral (control) – were activated. The results showed that activating women’s non-traditional social role increased their tendency to invest and decreased their propensity to save money compared to the activation of the traditional or neutral social role. The goal of the second study (n = 196 females) was to check whether, despite there being no differences in the level of consumption in the first study, can any differences be observed in the preference for the type of products chosen for consumption. The results showed that activating the non-traditional social role raised the propensity to spend funds on products and services for individual use and reduced the willingness to buy goods for collective use (shared with other members of the household). The purpose of the third study (n = 90 females) was to examine how different images of women appearing in advertisements may affect women’s judgments of the advertised product. Women who watched the ad with woman in the non-traditional social role estimated the product quality, look, color and price higher that participants exposed to the advertisement presenting the woman in traditional or neutral social role. The present studies give some evidence that the new, non-traditional social role of women that is often presented in the media may affect women’s everyday financial choices and judgments of products. PMID:27014168

Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.

PubMed

Xu, Lei; Ma, Xiaole; Zhao, Weihua; Luo, Lizhu; Yao, Shuxia; Kendrick, Keith M

2015-12-01

There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual-target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

FAST TRACK COMMUNICATION: Novel mechanism for nanoscale catalysis

NASA Astrophysics Data System (ADS)

Msezane, Alfred Z.; Felfli, Zineb; Sokolovski, Dmitri

2010-10-01

The interplay between Regge resonances and Ramsauer-Townsend minima in the electron elastic total cross sections for Au and Pd atoms along with their large electron affinities is proposed as the fundamental atomic mechanism responsible for the observed exceptional catalytic properties of Au nanoparticles and to explain why the combination Au-Pd possesses an even higher catalytic activity than Au or Pd separately when catalyzing H2O2, consistent with recent experiments. The investigation uses the recent complex angular momentum description of electron scattering from neutral atoms and the proposed mechanism in general.

Emotional states, attentional resources, and cognitive activity: a preliminary study.

PubMed

Versace, R; Monteil, J M; Mailhot, L

1993-06-01

This study explored the link between emotional state and attentional resources. A neutral or negative emotional state was induced in 50 subjects, then they performed a path-learning task followed by a word-memorization task while reproducing the prelearned path. Memory performance was assessed on a free-recall test. Analysis indicated that a previous induction of a negative emotional state disrupted path learning. Recall was not significantly affected by the subjects' emotional states, but recall was higher for subjects who had automatized the path prior to memorizing the words.

Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5

PubMed Central

Douglas, Alexander D.; Williams, Andrew R.; Knuepfer, Ellen; Illingworth, Joseph J.; Furze, Julie M.; Crosnier, Cécile; Choudhary, Prateek; Bustamante, Leyla Y.; Zakutansky, Sara E.; Awuah, Dennis K.; Alanine, Daniel G. W.; Theron, Michel; Worth, Andrew; Shimkets, Richard; Rayner, Julian C.; Holder, Anthony A.; Wright, Gavin J.; Draper, Simon J.

2013-01-01

There is intense interest in induction and characterization of strain-transcending neutralizing antibody against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) as a target of broadly-neutralizing antibodies, but there is little information regarding the functional mechanism(s) of antibody-mediated neutralization. Here, we report that vaccine-induced polyclonal anti-PfRH5 antibodies inhibit the tight attachment of merozoites to erythrocytes, and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 monoclonal antibodies (mAbs), we provide evidence that i) the ability to block the PfRH5-basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity; ii) neutralizing mAbs bind spatially-related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence; iii) a brief exposure window of PfRH5 is likely to necessitate rapid binding of antibody to neutralize parasites; and iv) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly-neutralizing anti-malaria antibodies and further encourage anti-PfRH5 based malaria prevention efforts. PMID:24293631

Healthy individuals treated with clomipramine: an fMRI study of brain activity during autobiographical recall of emotions.

PubMed

Cerqueira, C T; Sato, J R; de Almeida, J R C; Amaro, E; Leite, C C; Gorenstein, C; Gentil, V; Busatto, G F

2014-07-01

Various functional magnetic resonance imaging studies addressed the effects of antidepressant drugs on brain functioning in healthy subjects; however, none specifically investigated positive mood changes to antidepressant drug. Sixteen subjects with no personal or family history of psychiatric disorders were selected from an ongoing 4-week open trial of small doses of clomipramine. Follow-up interviews documented clear positive treatment effects in six subjects, with reduced irritability and tension in social interactions, improved decision making, higher self-confidence and brighter mood. These subjects were then included in a placebo-controlled confirmatory trial and were scanned immediately after 4 weeks of clomipramine use and again 4 weeks after the last dose of clomipramine. The functional magnetic resonance imaging (fMRI) scans were run during emotion-eliciting stimuli. Repeated-measures analysis of variance of brain activity patterns showed significant interactions between group and treatment status during induced irritability (P<0.005 cluster-based) but not during happiness. Individuals displaying a positive subjective response do clomipramine had higher frontoparietal cortex activity during irritability than during happiness and neutral emotion, and higher temporo-parieto-occipital cortex activity during irritability than during happiness. We conclude that antidepressants not only induce positive mood responses but also act upon autobiographical recall of negative emotions.

Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy.

PubMed

James, J H; Ziparo, V; Jeppsson, B; Fischer, J E

1979-10-13

It is proposed that hyperammonaemia in liver cirrhosis or after portacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral amino-acid transport system. Plasma neutral aminoacid concentrations are deranged, partly, but not completely, because ammonia stimulates glucagon secretion; a high rate of gluconeogenesis and hyperinsulinaemia follow. Brain uptake of neutral aminoacids rises because ammonia stimulates brain-glutamine synthesis, which results in rapid exchange of brain glutamine for plasma neutral aminoacids. Hyperammonaemia therefore contributes to encephalopathy indirectly, by raising the brain concentration of neutral aminoacids which after neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.

Emotional Memories Are Not All Created Equal: Evidence for Selective Memory Enhancement

ERIC Educational Resources Information Center

Anderson, Adam K.; Grabski, Wojtek; Lacka, Dominika; Yamaguchi, Yuki

2006-01-01

Human brain imaging studies have shown that greater amygdala activation to emotional relative to neutral events leads to enhanced episodic memory. Other studies have shown that fearful faces also elicit greater amygdala activation relative to neutral faces. To the extent that amygdala recruitment is sufficient to enhance recollection, these…

Dust dynamics and diagnostic applications in quasi-neutral plasmas and magnetic fusion

NASA Astrophysics Data System (ADS)

Wang, Zhehui; Ticos, Catalin M.; Si, Jiahe; Delzanno, Gian Luca; Lapenta, Gianni; Wurden, Glen

2007-11-01

Little is known about dust dynamics in highly ionized quasi-neutral plasmas with ca. 1.0 e+20 per cubic meter density and ion temperature at a few eV and above, including in magnetic fusion. For example, dust motion in fusion, better known as UFO's, has been observed since 1980's but not explained. Solid understanding of dust dynamics is also important to International Thermonuclear Experimental Reactor (ITER) because of concerns about safety and dust contamination of fusion core. Compared with well studied strongly-coupled dusty plasma regime, new physics may arise in the higher density quasi-neutral plasma regime because of at least four orders of magnitude higher density and two orders of magnitude hotter ion temperature. Our recent laboratory experiments showed that plasma-flow drag force dominates over other forces in a quasi-neutral flowing plasma. In contrast, delicate balance among different forces in dusty plasma has led to many unique phenomena, in particular, the formation of dust crystal. Based on our experiments, we argue that 1) dust crystal will not form in the highly ionized plasmas with flows; 2) the UFO's are moving dust dragged by plasma flows; 3) dust can be used to measure plasma flow. Two diagnostic applications using dust for laboratory quasi-neutral plasmas and magnetic fusion will also be presented.

Characterization of heat-induced interaction of neutral liposome with lipid membrane of Streptomyces griseus cell.

PubMed

Ngo, Kien Xuan; Umakoshi, Hiroshi; Shimanouchi, Toshinori; Kuboi, Ryoichi

2009-10-15

The interaction between the neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) liposomes and cell membrane of Streptomyces griseus induced by the heat treatment at specific temperature was investigated, focusing on the internalization of the neutral POPC liposomes with S. griseus cells. In an attempt to clarify the modes of liposome internalization, various kinds of inhibitors of endocytotic pathways were used to treat S. griseus cells. The efficiency of the heat treatment on liposome-cell membrane interactions was finally characterized based on the hydrophobic, electrostatic interactions and hydration effect. In fact, the internalization of the neutral liposomes into these cells was found to show higher rate and greater amount at higher temperatures. The kinetic study showed that the maximum amount of the internalized liposomes was, respectively, 469 x 10(5) and 643 x 10(5) liposomes/cell at 37 and 41 degrees C. The internalization of the neutral liposomes induced by the heat treatment was characterized, implying that the endocytosis occurred. The interactions involving the internalization, adsorption, and fusion of these liposomes with S. griseus cells were mainly contributed by the hydrophobic interaction and the unstable hydrogen bonds caused by the loss of water of surface hydration of cell membrane rather than the electrostatic interaction under the specific heat condition.

Antacid effects of Chinese herbal prescriptions assessed by a modified artificial stomach model

PubMed Central

Wu, Tsung-Hsiu; Chen, I-Chin; Chen, Lih-Chi

2010-01-01

AIM: To assess the antacid effects of the tonic Chinese herbal prescriptions, Si-Jun-Zi-Tang (SJZT) and Shen-Ling-Bai-Zhu-San (SLBZS). METHODS: Decoctions of the tonic Chinese herbal prescriptions, SJZT and SLBZS, were prepared according to Chinese original documents. The pH of the prescription decoctions and their neutralizing effects on artificial gastric acids were determined and compared with water and the active controls, sodium bicarbonate and colloidal aluminum phosphate. A modified model of Vatier’s artificial stomach was used to determine the duration of consistent neutralization effect on artificial gastric acids. The neutralization capacity in vitro was determined with the titration method of Fordtran’s model. RESULTS: The results showed that both SJZT and SLBZS have antacid effects in vitro. Compared with the water group, SJZT and SLBZS were found to possess significant gastric acid neutralizing effects. The duration for consistent neutralization of SLBZS was significantly longer than that of water. Also, SLBZS and SJZT exhibited significant antacid capacities compared to water. CONCLUSION: SJZT and SLBZS were consistently active in the artificial stomach model and are suggested to have antacid effects similar to the active control drugs. PMID:20845514

Anti-activin A antibody (IgY) specifically neutralizes various activin A activities.

PubMed

Murata, T; Saito, S; Shiozaki, M; Lu, R Z; Eto, Y; Funaba, M; Takahashi, M; Torii, K

1996-01-01

Activin A (beta A beta A), originally isolated from ovarian follicular fluids as a follicule-stimulating hormone (FSH) secretion stimulator, has also been identified as an erythroid differentiation factor (EDF), a neuron survival factor and a mesoderm-inducing factor. Thus, activin A is a multifunctional factor, and further studies on its physiological function are important. However, it is very difficult to produce a specific antibody to neutralize the activity of activin A because of its highly conserved amino acid sequence across mammalian species. In this study, we succeeded in generating an antibody against activin A, which can neutralize several activities of activin A, such as the stimulation of FSH secretion from pituitary cells and the induction of the differentiation of erythrocytes in vitro. This antibody did not affect the activity of activin B (beta B beta B), which induces the differentiation of erythrocytes in vitro, and the activity of inhibin A (alpha beta A), which inhibits FSH secretion from pituitary in vitro, but slightly neutralized that of activin AB (beta A beta B). Western blotting analysis showed that this antibody recognized both dimeric and monomeric forms of the beta A subunit of activin and inhibin. These results suggest that this antibody recognizes the beta A subunit of activin and specifically neutralizes the activity of a dimer of the beta A subunit, activin A. Furthermore, by the addition of this antibody to the culture medium, the development of murine embryos was suppressed, suggesting that endogenous activin A plays an important role in murine development. These results indicate the usefulness of this antibody for studies of endogenous activin actions.

A single bout of resistance exercise can enhance episodic memory performance.

PubMed

Weinberg, Lisa; Hasni, Anita; Shinohara, Minoru; Duarte, Audrey

2014-11-01

Acute aerobic exercise can be beneficial to episodic memory. This benefit may occur because exercise produces a similar physiological response as physical stressors. When administered during consolidation, acute stress, both physical and psychological, consistently enhances episodic memory, particularly memory for emotional materials. Here we investigated whether a single bout of resistance exercise performed during consolidation can produce episodic memory benefits 48 h later. We used a one-leg knee extension/flexion task for the resistance exercise. To assess the physiological response to the exercise, we measured salivary alpha amylase (a biomarker of central norepinephrine), heart rate, and blood pressure. To test emotional episodic memory, we used a remember-know recognition memory paradigm with equal numbers of positive, negative, and neutral IAPS images as stimuli. The group that performed the exercise, the active group, had higher overall recognition accuracy than the group that did not exercise, the passive group. We found a robust effect of valence across groups, with better performance on emotional items as compared to neutral items and no difference between positive and negative items. This effect changed based on the physiological response to the exercise. Within the active group, participants with a high physiological response to the exercise were impaired for neutral items as compared to participants with a low physiological response to the exercise. Our results demonstrate that a single bout of resistance exercise performed during consolidation can enhance episodic memory and that the effect of valence on memory depends on the physiological response to the exercise. Copyright © 2014 Elsevier B.V. All rights reserved.

Expeditious neutralization assay for human metapneumovirus based on a recombinant virus expressing Renilla luciferase.

PubMed

Zhou, Min; Kitagawa, Yoshinori; Yamaguchi, Mayu; Uchiyama, Chika; Itoh, Masae; Gotoh, Bin

2013-01-01

Human metapneumovirus (HMPV) is a common cause of respiratory diseases in persons of all ages. Because of its slow replication and weak cytopathic effect in cultured cells, conventional neutralization assays for HMPV require around one week for completion. The purpose of this study is to establish a rapid neutralization assay based on a recombinant virus expressing Renilla luciferase (Rluc). A recombinant HMPV expressing both Rluc and green fluorescent protein (GFP) was created by reverse genetics method. Two-fold serial dilutions of human 23 sera were made in a 96-well plate and incubated with 50 pfu/well of the recombinant virus at 4°C for 1 h. The mixtures were then transferred to LLC-MK2 cells in a 96-well plate, incubated for 2 h, and replaced with trypsin-free fresh media. After incubation at 32°C for 24 h, the cells were lysed and measured for Rluc activity. The neutralization titer was defined as the reciprocal of the highest serum dilution that resulted in 50% reduction of Rluc activity. The novel assay could be completed within 24 h and eliminated the requirement of trypsin supporting multistep replication in cultured cells, as well as laborious processes including the plaque assay with immunostaining. Neutralization titers correlated well with those determined by a GFP-based assay previously developed. The neutralization assay based on Rluc activity is the fastest and the most straightforward of all previous assays, and may be available for high throughput screening of neutralizing antibodies. Copyright © 2012 Elsevier B.V. All rights reserved.

Frontolimbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study

PubMed Central

Minzenberg, Michael J.; Fan, Jin; New, Antonia S.; Tang, Cheuk Y.; Siever, Larry J.

2007-01-01

Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of frontolimbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HC) viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HC) in the bilateral rostral/subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD. PMID:17601709

Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study.

PubMed

Minzenberg, Michael J; Fan, Jin; New, Antonia S; Tang, Cheuk Y; Siever, Larry J

2007-08-15

Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of fronto-limbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HC) viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HC) in the bilateral rostral/subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD.

Chemical acceleration of a neutral granulated blast-furnace slag activated by sodium carbonate

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

Kovtun, Maxim, E-mail: max.kovtun@up.ac.za; Kearsley, Elsabe P., E-mail: elsabe.kearsley@up.ac.za; Shekhovtsova, Julia, E-mail: j.shekhovtsova@gmail.com

2015-06-15

This paper presents results of a study on chemical acceleration of a neutral granulated blast-furnace slag activated using sodium carbonate. As strength development of alkali-activated slag cements containing neutral GBFS and sodium carbonate as activator at room temperature is known to be slow, three accelerators were investigated: sodium hydroxide, ordinary Portland cement and a combination of silica fume and slaked lime. In all cements, the main hydration product is C–(A)–S–H, but its structure varies between tobermorite and riversideite depending on the accelerator used. Calcite and gaylussite are present in all systems and they were formed due to either cation exchangemore » reaction between the slag and the activator, or carbonation. With accelerators, compressive strength up to 15 MPa can be achieved within 24 h in comparison to 2.5 MPa after 48 h for a mix without an accelerator.« less

Does modulation of selective attention to features reflect enhancement or suppression of neural activity?

PubMed

Daffner, Kirk R; Zhuravleva, Tatyana Y; Sun, Xue; Tarbi, Elise C; Haring, Anna E; Rentz, Dorene M; Holcomb, Phillip J

2012-02-01

Numerous studies have demonstrated that selective attention to color is associated with a larger neural response under attend than ignore conditions, but have not addressed whether this difference reflects enhanced activity under attend or suppressed activity under ignore. In this study, a color-neutral condition was included, which presented stimuli physically identical to those under attend and ignore conditions, but in which color was not task relevant. Attention to color did not modulate the early sensory-evoked P1 and N1 components. Traditional ERP markers of early selection (the anterior Selection Positivity and posterior Selection Negativity) did not differ between the attend and neutral conditions, arguing against a mechanism of enhanced activity. However, there were markedly reduced responses under the ignore relative to the neutral condition, consistent with the view that early selection mechanisms reflect suppression of neural activity under the ignore condition. Copyright © 2011 Elsevier B.V. All rights reserved.

The Potential of Microalgae Lipids for Edible Oil Production.

PubMed

Huang, Yanfei; Zhang, Dongmei; Xue, Shengzhang; Wang, Meng; Cong, Wei

2016-10-01

The objective of this study was to evaluate the potential of oil-rich green algae, Chlorella vulgaris, Scenedesmus obliquus, and Nannochloropsis oceanica, to produce edible oil with respect to lipid and residue properties. The results showed that C. vulgaris and N. oceanica had similarly much higher lipid recovery (about 50 %) in hexane extraction than that of S. obliquus (about 25 %), and C. vulgaris had the highest content of neutral lipids among the three algae. The fatty acid compositions of neutral lipids from C. vulgaris and S. obliquus were mainly C16 and C18, resembling that of vegetable oils. ARA and EPA were the specific valuable fatty acids in lipids of N. oceanica, but the content of which was lower in neutral lipids. Phytol was identified as the major unsaponifiable component in lipids of the three algae. Combined with the evaluation of the ratios in SFA/MUFA/PUFA, (n-6):(n-3) and content of free fatty acids, lipids obtained from C. vulgaris displayed the great potential for edible oil production. Lipids of N. oceanica showed the highest antioxidant activity, and its residue contained the largest amounts of protein as well as the amino acid compositions were greatly beneficial to the health of human beings.

Always look on the broad side of life: happiness increases the breadth of sensory memory.

PubMed

Kuhbandner, Christof; Lichtenfeld, Stephanie; Pekrun, Reinhard

2011-08-01

Research has shown that positive affect increases the breadth of information processing at several higher stages of information processing, such as attentional selection or knowledge activation. In the present study, we examined whether these affective influences are already present at the level of transiently storing incoming information in sensory memory, before attentional selection takes place. After inducing neutral, happy, or sad affect, participants performed an iconic memory task which measures visual sensory memory. In all conditions, iconic memory performance rapidly decreased with increasing delay between stimulus presentation and test, indicating that affect did not influence the decay of iconic memory. However, positive affect increased the amount of incoming information stored in iconic memory. In particular, our results showed that this occurs due to an elimination of the spatial bias typically observed in iconic memory. Whereas performance did not differ at positions where observers in the neutral and negative conditions showed the highest performance, positive affect enhanced performance at all positions where observers in the neutral and negative conditions were relatively "blind." These findings demonstrate that affect influences the breadth of information processing already at earliest processing stages, suggesting that affect may produce an even more fundamental shift in information processing than previously believed. 2011 APA, all rights reserved

Biological and genetic evolution of HIV type 1 in two siblings with different patterns of disease progression.

PubMed

Ripamonti, Chiara; Leitner, Thomas; Laurén, Anna; Karlsson, Ingrid; Pastore, Angela; Cavarelli, Mariangela; Antonsson, Liselotte; Plebani, Anna; Fenyö, Eva Maria; Scarlatti, Gabriella

2007-12-01

To investigate the immunological and virological factors that may lead to different patterns of disease progression characteristic of HIV-1-infected children, two HIV-1-infected siblings, a slow and a fast progressor, were followed prospectively before the onset of highly active antiretroviral therapy. Viral coreceptor usage, including the use of CCR5/CXCR4 chimeric receptors, macrophage tropism, and sensitivity to the CC-chemokine RANTES, has been studied. An autologous and heterologous neutralizing antibody response has been documented using peripheral blood mononuclear cells- and GHOST(3) cell line-based assays. Viral evolution was investigated by env C2-V3 region sequence analysis. Although both siblings were infected with HIV-1 of the R5 phenotype, their viruses showed important biological differences. In the fast progressor there was a higher RANTES sensitivity of the early virus, an increased trend to change the mode of CCR5 receptor use, and a larger genetic evolution. Both children developed an autologous neutralizing antibody response starting from the second year with evidence of the continuous emergence of resistant variants. A marked viral genetic and phenotypic evolution was documented in the fast progressor sibling, which is accompanied by a high viral RANTES sensitivity and persistent neutralizing antibodies.

Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis.

PubMed

De Benedictis, Paola; Minola, Andrea; Rota Nodari, Elena; Aiello, Roberta; Zecchin, Barbara; Salomoni, Angela; Foglierini, Mathilde; Agatic, Gloria; Vanzetta, Fabrizia; Lavenir, Rachel; Lepelletier, Anthony; Bentley, Emma; Weiss, Robin; Cattoli, Giovanni; Capua, Ilaria; Sallusto, Federica; Wright, Edward; Lanzavecchia, Antonio; Bourhy, Hervé; Corti, Davide

2016-04-01

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response. © 2016 Humabs BioMed SA Published under the terms of the CC BY 4.0 license.

Neutral-depletion-induced axially asymmetric density in a helicon source and imparted thrust

NASA Astrophysics Data System (ADS)

Takahashi, Kazunori; Takao, Yoshinori; Ando, Akira

2016-02-01

The high plasma density downstream of the source is observed to be sustained only for a few hundreds of microsecond at the initial phase of the discharge, when pulsing the radiofrequency power of a helicon plasma thruster. Measured relative density of argon neutrals inside the source implies that the neutrals are significantly depleted there. A position giving a maximum plasma density temporally moves to the upstream side of the source due to the neutral depletion and then the exhausted plasma density significantly decreases. The direct thrust measurement demonstrates that the higher thrust-to-power ratio is obtained by using only the initial phase of the high density plasma, compared with the steady-state operation.

Structural and electronic properties Te62+ and Te82+: A DFT study

NASA Astrophysics Data System (ADS)

Sharma, Tamanna; Tamboli, Rohit; Kanhere, D. G.; Sharma, Raman

2018-05-01

Structural and electronic properties of Tellurium cluster (Ten) and their cations (Ten2+) (n = 6, 8) have been studied theoretically using VASP within generalized gradient approximation. Ground state geometries and higher energy isomers of these clusters have been examined on the basis of total free energy calculations. Lowest energy isomers of neutral clusters are ring like structures whereas the lowest energy isomers of cations are polyhedral cages. HOMO-LUMO gap in cationic clusters is small compared to its neutral clusters. Removal of two electrons from the neutral cluster raises the free energy. Analysis of free energy, HOMO-LUMO gap and density of states (DOS) show that neutral cluster are more stable than their cations.

Ionospheric plasma cloud dynamics

NASA Technical Reports Server (NTRS)

1976-01-01

Measurements of the thermospheric neutral wind and ionospheric drift made at Eglin AFB, Florida and Kwajalein Atoll are discussed. The neutral wind measurements at Eglin had little variation over a period of four years for moderate magnetic activity (Kp 4); the ionospheric drifts are small. Evidence is presented that indicates that increased magnetic activity has a significant effect on the neutral wind magnitude and direction at this midlatitude station. The neutral wind at dusk near the equator is generally small although in one case out of seven it was significantly larger. It is described how observations of large barium releases can be used to infer the degree of electrodynamic coupling of ion clouds to the background ionosphere. Evidence is presented that indicates that large barium releases are coupled to the conjugate ionosphere at midlatitudes.

Correlation between urinary GAG and anti-idursulfase ERT neutralizing antibodies during treatment with NICIT immune tolerance regimen: A case report☆,☆☆

PubMed Central

Kim, Sarah; Whitley, Chester B.; Jarnes Utz, Jeanine R.

2018-01-01

Introduction Antibodies to intravenous idursulfase enzyme replacement therapy (ERT) for patients with Hunter syndrome (mucopolysaccharidosis type II, MPS II) can have a harmful clinical impact, including both increasing risk of infusion reactions and inhibiting therapeutic activity. Thus, failure to monitor anti-idursulfase antibodies and neutralizing antibodies, and delays in reporting results, may postpone critical clinical decisions. Hypothesis Urinary glycosaminoglycan (GAG) levels may be used as a biomarker for anti-idursulfase antibodies and neutralizing antibodies to improve timeliness in monitoring and managing ERT. Methods This is a case report describing a patient with MPS II with high levels of neutralizing antibodies and worsened clinical status who was treated for five years with a non-immunosuppressive and non-cytotoxic immune tolerance (NICIT) regimen, consisting of intravenous immune globulin and frequent infusions of idursulfase. Neutralizing antibodies and total anti-idursulfase antibodies were measured by two different methods, the direct 1,9-dimethylmethylene blue (DMB) assay and cetylpyridinium chloride carbazole-borate (CPC) assay. Results Neutralizing antibodies, measured as percent inhibition of enzyme activity and also by total neutralizing antibody titer, were correlated with quantitative urinary GAG measured by DMB assay (p = 0.026, p = 0.0067), and quantitative urinary GAG by CPC assay with percent inhibition of enzyme activity by neutralizing antibodies (p = 0.0475). The NICIT regimen showed a sustained immune tolerance after five years and was well-tolerated. Conclusions Urinary GAG, measured by DMB assay, may be a biomarker for anti-idursulfase neutralizing antibodies and is useful for managing immune tolerance regimens for patients with MPS II who have high levels of anti-idursulfase neutralizing antibodies. This study highlights the importance of regular and frequent monitoring of urinary GAG in patients with MPS II who are receiving ERT. The NICIT regimen, with less drug toxicities, may be preferred in patients with MPS who have a high risk of infections and whose disease progresses less rapidly than some other lysosomal storage diseases, such as infantile Pompe disease. PMID:28610913

Alpha-ketoglutarate reduces ethanol toxicity in Drosophila melanogaster by enhancing alcohol dehydrogenase activity and antioxidant capacity.

PubMed

Bayliak, Maria M; Shmihel, Halyna V; Lylyk, Maria P; Storey, Kenneth B; Lushchak, Volodymyr I

2016-09-01

Ethanol at low concentrations (<4%) can serve as a food source for fruit fly Drosophila melanogaster, whereas at higher concentrations it may be toxic. In this work, protective effects of dietary alpha-ketoglutarate (AKG) against ethanol toxicity were studied. Food supplementation with 10-mM AKG alleviated toxic effects of 8% ethanol added to food, and improved fly development. Two-day-old adult flies, reared on diet containing both AKG and ethanol, possessed higher alcohol dehydrogenase (ADH) activity as compared with those reared on control diet or diet with ethanol only. Native gel electrophoresis data suggested that this combination diet might promote post-translational modifications of ADH protein with the formation of a highly active ADH form. The ethanol-containing diet led to significantly higher levels of triacylglycerides stored in adult flies, and this parameter was not altered by AKG supplement. The influence of diet on antioxidant defenses was also assessed. In ethanol-fed flies, catalase activity was higher in males and the levels of low molecular mass thiols were unchanged in both sexes compared to control values. Feeding on a mixture of AKG and ethanol did not affect catalase activity but caused a higher level of low molecular mass thiols compared to ethanol-fed flies. It can be concluded that both a stimulation of some components of antioxidant defense and the increase in ADH activity may be responsible for the protective effects of AKG diet supplementation in combination with ethanol. The results suggest that AKG might be useful as a treatment option to neutralize toxic effects of excessive ethanol intake and to improve the physiological state of D. melanogaster and other animals, potentially including humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral Arginine Metabolism May Decrease the Risk for Dental Caries in Children

PubMed Central

Nascimento, M.M.; Liu, Y.; Kalra, R.; Perry, S.; Adewumi, A.; Xu, X.; Primosch, R.E.; Burne, R.A.

2013-01-01

Arginine metabolism by oral bacteria via the arginine deiminase system (ADS) increases the local pH, which can neutralize the effects of acidification from sugar metabolism and reduce the cariogenicity of oral biofilms. To explore the relationship between oral arginine metabolism and dental caries experience in children, we measured ADS activity in oral samples from 100 children and correlated it with their caries status and type of dentition. Supragingival dental plaque was collected from tooth surfaces that were caries-lesion-free (PF) and from dentinal (PD) and enamel (PE) caries lesions. Regardless of children’s caries status or type of dentition, PF (378.6) had significantly higher ADS activity compared with PD (208.4; p < .001) and PE (194.8; p = .005). There was no significant difference in the salivary arginolytic activity among children with different caries status. Mixed-model analysis showed that plaque caries status is significantly associated with ADS activity despite children’s age, caries status, and dentition (p < .001), with healthy plaque predicting higher ADS activity compared with diseased plaque. Plaque arginine metabolism varies greatly among children and tooth sites, which may affect their susceptibility to caries. PMID:23640952

Changes in Corticospinal and Spinal Excitability to the Biceps Brachii with a Neutral vs. Pronated Handgrip Position Differ between Arm Cycling and Tonic Elbow Flexion

PubMed Central

Forman, Davis A.; Richards, Mark; Forman, Garrick N.; Holmes, Michael W. R.; Power, Kevin E.

2016-01-01

The purpose of this study was to examine the influence of neutral and pronated handgrip positions on corticospinal excitability to the biceps brachii during arm cycling. Corticospinal and spinal excitability were assessed using motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation (TMS) and cervicomedullary-evoked potentials (CMEPs) elicited via transmastoid electrical stimulation (TMES), respectively. Participants were seated upright in front on arm cycle ergometer. Responses were recorded from the biceps brachii at two different crank positions (6 and 12 o’clock positions relative to a clock face) while arm cycling with neutral and pronated handgrip positions. Responses were also elicited during tonic elbow flexion to compare/contrast the results to a non-rhythmic motor output. MEP and CMEP amplitudes were significantly larger at the 6 o’clock position while arm cycling with a neutral handgrip position compared to pronated (45.6 and 29.9%, respectively). There were no differences in MEP and CMEP amplitudes at the 12 o’clock position for either handgrip position. For the tonic contractions, MEPs were significantly larger with a neutral vs. pronated handgrip position (32.6% greater) while there were no difference in CMEPs. Corticospinal excitability was higher with a neutral handgrip position for both arm cycling and tonic elbow flexion. While spinal excitability was also higher with a neutral handgrip position during arm cycling, no difference was observed during tonic elbow flexion. These findings suggest that not only is corticospinal excitability to the biceps brachii modulated at both the supraspinal and spinal level, but that it is influenced differently between rhythmic arm cycling and tonic elbow flexion. PMID:27826236

Inertia-Centric Stability Analysis of a Planar Uniform Dust Molecular Cloud with Weak Neutral-Charged Dust Frictional Coupling

NASA Astrophysics Data System (ADS)

K. Karmakar, P.; Borah, B.

2014-05-01

This paper adopts an inertia-centric evolutionary model to study the excitation mechanism of new gravito-electrostatic eigenmode structures in a one-dimensional (1-D) planar self-gravitating dust molecular cloud (DMC) on the Jeans scale. A quasi-neutral multi-fluid consisting of warm electrons, warm ions, neutral gas and identical inertial cold dust grains with partial ionization is considered. The grain-charge is assumed not to vary at the fluctuation evolution time scale. The neutral gas particles form the background, which is weakly coupled with the collapsing grainy plasma mass. The gravitational decoupling of the background neutral particles is justifiable for a higher inertial mass of the grains with higher neutral population density so that the Jeans mode frequency becomes reasonably large. Its physical basis is the Jeans assumption of a self-gravitating uniform medium adopted for fiducially analytical simplification by neglecting the zero-order field. So, the equilibrium is justifiably treated initially as “homogeneous”. The efficacious inertial role of the thermal species amidst weak collisions of the neutral-charged grains is taken into account. A standard multiscale technique over the gravito-electrostatic equilibrium yields a unique pair of Korteweg-de Vries (KdV) equations. It is integrated numerically by the fourth-order Runge-Kutta method with multi-parameter variation for exact shape analyses. Interestingly, the model is conducive for the propagation of new conservative solitary spectral patterns. Their basic physics, parametric features and unique characteristics are discussed. The results go qualitatively in good correspondence with the earlier observations made by others. Tentative applications relevant to space and astrophysical environments are concisely highlighted.

Neutral Theory and Scale-Free Neural Dynamics

NASA Astrophysics Data System (ADS)

Martinello, Matteo; Hidalgo, Jorge; Maritan, Amos; di Santo, Serena; Plenz, Dietmar; Muñoz, Miguel A.

2017-10-01

Neural tissues have been consistently observed to be spontaneously active and to generate highly variable (scale-free distributed) outbursts of activity in vivo and in vitro. Understanding whether these heterogeneous patterns of activity stem from the underlying neural dynamics operating at the edge of a phase transition is a fascinating possibility, as criticality has been argued to entail many possible important functional advantages in biological computing systems. Here, we employ a well-accepted model for neural dynamics to elucidate an alternative scenario in which diverse neuronal avalanches, obeying scaling, can coexist simultaneously, even if the network operates in a regime far from the edge of any phase transition. We show that perturbations to the system state unfold dynamically according to a "neutral drift" (i.e., guided only by stochasticity) with respect to the background of endogenous spontaneous activity, and that such a neutral dynamics—akin to neutral theories of population genetics and of biogeography—implies marginal propagation of perturbations and scale-free distributed causal avalanches. We argue that causal information, not easily accessible to experiments, is essential to elucidate the nature and statistics of neural avalanches, and that neutral dynamics is likely to play an important role in the cortex functioning. We discuss the implications of these findings to design new empirical approaches to shed further light on how the brain processes and stores information.

The neural representation of emotionally neutral faces and places in patients with panic disorder with agoraphobia.

PubMed

Petrowski, Katja; Wintermann, Gloria; Smolka, Michael N; Huebner, Thomas; Donix, Markus

2014-01-01

Panic disorder with agoraphobia (PD-A) has been associated with abnormal neural activity for threat-related stimuli (faces, places). Recent findings suggest a disturbed neural processing of emotionally neutral stimuli at a more general level. Using functional magnetic resonance imaging (fMRI) we investigated the neural processing of emotionally neutral faces and places in PD-A. Fifteen patients with PD-A and fifteen healthy subjects participated in the study. When they perceived neutral faces and places, the patients with PD-A showed significantly less brain activity in the fusiform gyrus, the inferior occipital gyrus, the calcarine gyrus, the cerebellum, and the cuneus compared with the healthy controls. However, the patients with PD-A showed significantly more brain activity in the precuneus compared with controls subjects. It was not possible to distinguish the agoraphobia-associated effects from possible contributions due to general anxiety induced by fMRI. For future investigations, an additional clinical control group with patients suffering from panic disorder without agoraphobia would be of interest. In addition, the psychopathology concerning the agoraphobic symptoms needs to be investigated in more detail. The findings suggest altered neural processing of emotionally neutral faces and places in patients with PD-A. Reduced neural activity in different brain regions may indicate difficulties in recognizing the emotional content in face and place stimuli due to anxiety-related hyper-arousal. © 2013 Published by Elsevier B.V.

Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies

PubMed Central

Chervyakova, Olga V.; Zaitsev, Valentin L.; Iskakov, Bulat K.; Tailakova, Elmira T.; Strochkov, Vitaliy M.; Sultankulova, Kulyaisan T.; Sandybayev, Nurlan T.; Stanbekova, Gulshan E.; Beisenov, Daniyar K.; Abduraimov, Yergali O.; Mambetaliyev, Muratbay; Sansyzbay, Abylay R.; Kovalskaya, Natalia Y.; Nemchinov, Lev. G.; Hammond, Rosemarie W.

2016-01-01

The aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (SPPV; genus Capripoxvirus, family Poxviridae) structural proteins as candidate subunit vaccines to control sheep pox disease. SPPV structural proteins were identified by sequence homology with proteins of vaccinia virus (VACV) strain Copenhagen. Four SPPV proteins (SPPV-ORF 060, SPPV-ORF 095, SPPV-ORF 117, and SPPV-ORF 122), orthologs of immunodominant L1, A4, A27, and A33 VACV proteins, respectively, were produced in Escherichia coli. Western blot analysis revealed the antigenic and immunogenic properties of SPPV-060, SPPV-095, SPPV-117 and SPPV-122 proteins when injected with adjuvant into experimental rabbits. Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. PMID:27338444

Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies.

PubMed

Chervyakova, Olga V; Zaitsev, Valentin L; Iskakov, Bulat K; Tailakova, Elmira T; Strochkov, Vitaliy M; Sultankulova, Kulyaisan T; Sandybayev, Nurlan T; Stanbekova, Gulshan E; Beisenov, Daniyar K; Abduraimov, Yergali O; Mambetaliyev, Muratbay; Sansyzbay, Abylay R; Kovalskaya, Natalia Y; Nemchinov, Lev G; Hammond, Rosemarie W

2016-06-07

The aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (SPPV; genus Capripoxvirus, family Poxviridae) structural proteins as candidate subunit vaccines to control sheep pox disease. SPPV structural proteins were identified by sequence homology with proteins of vaccinia virus (VACV) strain Copenhagen. Four SPPV proteins (SPPV-ORF 060, SPPV-ORF 095, SPPV-ORF 117, and SPPV-ORF 122), orthologs of immunodominant L1, A4, A27, and A33 VACV proteins, respectively, were produced in Escherichia coli. Western blot analysis revealed the antigenic and immunogenic properties of SPPV-060, SPPV-095, SPPV-117 and SPPV-122 proteins when injected with adjuvant into experimental rabbits. Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins.

A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos.

PubMed

Li, Cui; Gao, Fei; Yu, Lei; Wang, Ruoke; Jiang, Yisheng; Shi, Xuanling; Yin, Chibiao; Tang, Xiaoping; Zhang, Fuchun; Xu, Zhiheng; Zhang, Linqi

2018-05-01

Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, an emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. There is now an urgent need for prophylactic and therapeutic agents. To address this, we investigated six human monoclonal antibodies with ZIKV epitope specificity and neutralizing activity in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The Relationship between Neutralization Techniques and Induced Abortion

PubMed Central

Kalateh Sadati, Ahmad; Tabei, Seyed Ziaaddin; Salehzadeh, Hamzeh; Rahnavard, Farnaz; Namavar Jahromi, Bahia; Hemmati, Soroor

2014-01-01

Background: Induced abortion is not only a serious threat for women’s health, but also a controversial topic for its ethical and moral problems. We aimed to evaluate the relationship between neutralization techniques and attempting to commit abortion in married women with unintended pregnancy. Methods: After in-depth interviews with some women who had attempted abortion, neutralization themes were gathered. Next, to analyze the data quantitatively, a questionnaire was created including demographic and psychosocial variables specifically related to neutralization. The participants were divided into two groups (abortion and control) of unintended pregnancy and were then compared. Results: Analysis of psychosocial variables revealed a significant difference in the two groups at neutralization, showing that neutralization in the control group (56.97±10.24) was higher than that in the abortion group (44.19±12.44). To evaluate the findings more accurately, we examined the causal factors behind the behaviors of the abortion group. Binary logistic regression showed that among psychosocial factors, neutralization significantly affected abortion (95% CI=1.07-1.35). Conclusion: Despite the network of many factors affecting induced abortion, neutralization plays an important role in reinforcing the tendency to attempt abortion. Furthermore, the decline of religious beliefs, as a result of the secular context of the modern world, seems to have an important role in neutralizing induced abortion. PMID:25349851

Serologic evidence of Lyssavirus infections among bats, the Philippines.

PubMed

Arguin, Paul M; Murray-Lillibridge, Kristy; Miranda, Mary E G; Smith, Jean S; Calaor, Alan B; Rupprecht, Charles E

2002-03-01

Active surveillance for lyssaviruses was conducted among populations of bats in the Philippines. The presence of past or current Lyssavirus infection was determined by use of direct fluorescent antibody assays on bat brains and virus neutralization assays on bat sera. Although no bats were found to have active infection with a Lyssavirus, 22 had evidence of neutralizing antibody against the Australian bat lyssavirus (ABLV). Seropositivity was statistically associated with one species of bat, Miniopterus schreibersi. Results from the virus neutralization assays are consistent with the presence in the Philippines of a naturally occurring Lyssavirus related to ABLV.

Serologic Evidence of Lyssavirus Infections among Bats, the Philippines

PubMed Central

Murray-Lillibridge, Kristy; Miranda, Mary E.G.; Smith, Jean S.; Calaor, Alan B.; Rupprecht, Charles E.

2002-01-01

Active surveillance for lyssaviruses was conducted among populations of bats in the Philippines. The presence of past or current Lyssavirus infection was determined by use of direct fluorescent antibody assays on bat brains and virus neutralization assays on bat sera. Although no bats were found to have active infection with a Lyssavirus, 22 had evidence of neutralizing antibody against the Australian bat lyssavirus (ABLV). Seropositivity was statistically associated with one species of bat, Miniopterus schreibersi. Results from the virus neutralization assays are consistent with the presence in the Philippines of a naturally occurring Lyssavirus related to ABLV. PMID:11927022

The effects of sample size on population genomic analyses--implications for the tests of neutrality.

PubMed

Subramanian, Sankar

2016-02-20

One of the fundamental measures of molecular genetic variation is the Watterson's estimator (θ), which is based on the number of segregating sites. The estimation of θ is unbiased only under neutrality and constant population growth. It is well known that the estimation of θ is biased when these assumptions are violated. However, the effects of sample size in modulating the bias was not well appreciated. We examined this issue in detail based on large-scale exome data and robust simulations. Our investigation revealed that sample size appreciably influences θ estimation and this effect was much higher for constrained genomic regions than that of neutral regions. For instance, θ estimated for synonymous sites using 512 human exomes was 1.9 times higher than that obtained using 16 exomes. However, this difference was 2.5 times for the nonsynonymous sites of the same data. We observed a positive correlation between the rate of increase in θ estimates (with respect to the sample size) and the magnitude of selection pressure. For example, θ estimated for the nonsynonymous sites of highly constrained genes (dN/dS < 0.1) using 512 exomes was 3.6 times higher than that estimated using 16 exomes. In contrast this difference was only 2 times for the less constrained genes (dN/dS > 0.9). The results of this study reveal the extent of underestimation owing to small sample sizes and thus emphasize the importance of sample size in estimating a number of population genomic parameters. Our results have serious implications for neutrality tests such as Tajima D, Fu-Li D and those based on the McDonald and Kreitman test: Neutrality Index and the fraction of adaptive substitutions. For instance, use of 16 exomes produced 2.4 times higher proportion of adaptive substitutions compared to that obtained using 512 exomes (24% vs 10 %).

Ricin-Holotoxin-Based Vaccines: Induction of Potent Ricin-Neutralizing Antibodies.

PubMed

Sabo, Tamar; Kronman, Chanoch; Mazor, Ohad

2016-01-01

Ricin is one of the most potent and lethal toxins known to which there is no available antidote. Currently, the most promising therapy is based on neutralizing antibodies elicited by active vaccination or given passively. Here, detailed protocols are provided for the production of two ricin holotoxin-based vaccines: monomerized subunit-based vaccine, and a formaldehyde-based ricin toxoid vaccine. Both vaccines were found to be stable with no toxic activity reversion even after long-term storage while eliciting high anti-ricin antibody titers possessing a potent neutralizing activity. The use of these vaccines is highly suitable for both the production of sera that can be used in passive protection experiments and immunization aimed to isolate potent anti-ricin monoclonal antibodies.

Organic matter in sediment layers of an acidic mining lake as assessed by lipid analysis. Part II: Neutral lipids.

PubMed

Poerschmann, Juergen; Koschorreck, Matthias; Górecki, Tadeusz

2017-02-01

Natural neutralization of acidic mining lakes is often limited by organic matter. The knowledge of the sources and degradability of organic matter is crucial for understanding alkalinity generation in these lakes. Sediments collected at different depths (surface sediment layer from 0 to 1 cm and deep sediment layer from 4 to 5cm) from an acidic mining lake were studied in order to characterize sedimentary organic matter based on neutral signature markers. Samples were exhaustively extracted, subjected to pre-chromatographic derivatizations and analyzed by GC/MS. Herein, molecular distributions of diagnostic alkanes/alkenes, terpenes/terpenoids, polycyclic aromatic hydrocarbons, aliphatic alcohols and ketones, sterols, and hopanes/hopanoids were addressed. Characterization of the contribution of natural vs. anthropogenic sources to the sedimentary organic matter in these extreme environments was then possible based on these distributions. With the exception of polycyclic aromatic hydrocarbons, combined concentrations across all marker classes proved higher in the surface sediment layer as compared to those in the deep sediment layer. Alkane and aliphatic alcohol distributions pointed to predominantly allochthonous over autochthonous contribution to sedimentary organic matter. Sterol patterns were dominated by phytosterols of terrestrial plants including stigmasterol and β-sitosterol. Hopanoid markers with the ββ-biohopanoid "biological" configuration were more abundant in the surface sediment layer, which pointed to higher bacterial activity. The pattern of polycyclic aromatic hydrocarbons pointed to prevailing anthropogenic input. Pyrolytic makers were likely to due to atmospheric deposition from a nearby former coal combustion facility. The combined analysis of the array of biomarkers provided new insights into the sources and transformations of organic matter in lake sediments. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of spatial frequency information for ERP components sensitive to faces and emotional facial expression.

PubMed

Holmes, Amanda; Winston, Joel S; Eimer, Martin

2005-10-01

To investigate the impact of spatial frequency on emotional facial expression analysis, ERPs were recorded in response to low spatial frequency (LSF), high spatial frequency (HSF), and unfiltered broad spatial frequency (BSF) faces with fearful or neutral expressions, houses, and chairs. In line with previous findings, BSF fearful facial expressions elicited a greater frontal positivity than BSF neutral facial expressions, starting at about 150 ms after stimulus onset. In contrast, this emotional expression effect was absent for HSF and LSF faces. Given that some brain regions involved in emotion processing, such as amygdala and connected structures, are selectively tuned to LSF visual inputs, these data suggest that ERP effects of emotional facial expression do not directly reflect activity in these regions. It is argued that higher order neocortical brain systems are involved in the generation of emotion-specific waveform modulations. The face-sensitive N170 component was neither affected by emotional facial expression nor by spatial frequency information.

Etching Characteristics of VO2 Thin Films Using Inductively Coupled Cl2/Ar Plasma

NASA Astrophysics Data System (ADS)

Ham, Yong-Hyun; Efremov, Alexander; Min, Nam-Ki; Lee, Hyun Woo; Yun, Sun Jin; Kwon, Kwang-Ho

2009-08-01

A study on both etching characteristics and mechanism of VO2 thin films in the Cl2/Ar inductively coupled plasma was carried. The variable parameters were gas pressure (4-10 mTorr) and input power (400-700 W) at fixed bias power of 150 W and initial mixture composition of 25% Cl2 + 75% Ar. It was found that an increase in both gas pressure and input power results in increasing VO2 etch rate while the etch selectivity over photoresist keeps a near to constant values. Plasma diagnostics by Langmuir probes and zero-dimensional plasma model provided the data on plasma parameters, steady-state densities and fluxes of active species on the etched surface. The model-based analysis of the etch mechanism showed that, for the given ranges of operating conditions, the VO2 etch kinetics corresponds to the transitional regime of ion-assisted chemical reaction and is influenced by both neutral and ion fluxes with a higher sensitivity to the neutral flux.

Advanced oxidation of biorefractory organics in aqueous solution together with bioelectricity generation by microbial fuel cells with composite FO/GPEs

NASA Astrophysics Data System (ADS)

Fu, Bao-rong; Shen, Chao; Ren, Jing; Chen, Jia-yi; Zhao, Lin

2018-03-01

In this study, ferric oxide loading graphite particle electrodes (FO/GPEs) were prepared as cathode of a three-dimensional electrode MFC-Fenton system. The properties of the composite cathode were examined with higher surface area and more mesopores. FO/GPEs could work as both cathode and Fenton iron reagents, contributing to high oxidation activity and better performance of electricity generation. The application of FO/GPEs MFC-Fenton system on degrading p-nitrophenol presented high catalytic efficiency in a wide range of pH value. The removal of p-nitrophenol and TOC attained to about 85 % within 8 and 64 h at neutral pH, respectively. A neutral FO/GPEs MFC-Fenton oxidation mechanism was also proposed. Specifically, both the surface iron sites and dissolved iron ions catalyzed the decomposition of H2O2. As results, the generated hydroxyl radicals were used for p-nitrophenol degradation and the iron oxide was recycled.

Awareness of Emotional Stimuli Determines the Behavioral Consequences of Amygdala Activation and Amygdala-Prefrontal Connectivity

PubMed Central

Lapate, R. C.; Rokers, B.; Tromp, D. P. M.; Orfali, N. S.; Oler, J. A.; Doran, S. T.; Adluru, N.; Alexander, A. L.; Davidson, R. J.

2016-01-01

Conscious awareness of negative cues is thought to enhance emotion-regulatory capacity, but the neural mechanisms underlying this effect are unknown. Using continuous flash suppression (CFS) in the MRI scanner, we manipulated visual awareness of fearful faces during an affect misattribution paradigm, in which preferences for neutral objects can be biased by the valence of a previously presented stimulus. The amygdala responded to fearful faces independently of awareness. However, when awareness of fearful faces was prevented, individuals with greater amygdala responses displayed a negative bias toward unrelated novel neutral faces. In contrast, during the aware condition, inverse coupling between the amygdala and prefrontal cortex reduced this bias, particularly among individuals with higher structural connectivity in the major white matter pathway connecting the prefrontal cortex and amygdala. Collectively, these results indicate that awareness promotes the function of a critical emotion-regulatory network targeting the amygdala, providing a mechanistic account for the role of awareness in emotion regulation. PMID:27181344

Upgrades to the MARIA Helicon Experiment at UW-Madison

NASA Astrophysics Data System (ADS)

Green, Jonathan; Hershkowitz, Noah; Schmitz, Oliver; Severn, Greg; Winters, Victoria

2016-10-01

The MARIA helicon plasma device at UW Madison is setup to investigate the neutral particle fueling of helicon discharges. Following initial results from the 668.614nm diode laser LIF system, the active spectroscopy diagnostic suite was expanded by establishing a 1.4J pulsed Nd:YAG pumped dye laser. To verify the new laser system, a comparison of measured ion velocities near a target plate was made between the diode based and dye based LIF systems. Additionally, theory and further verification of a new technique for measuring ion velocities leveraging Zeeman splitting is presented. During a campaign with <= 750W RF power, densities in the range of 1x1018 m-3 and 2 eV electron temperature were achieved with 4.1 mTorr of argon and a magnetic field of 750G. To achieve higher densities and explore the physics of neutral depletion, the available RF power was increased from 750W to 2kW, with further expansion to 4kW on a single antenna planned. For both power levels a clear helicon mode can be reliably established and its extension increases with increasing RF power. Basic plasma characterization at the higher RF power, such as electron density vs magnetic field scans, will be presented. This work was funded by the NSF CAREER Award PHY-1455210.

Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years.

PubMed

Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Edwards, Robert P; Zepp, Fred; Carletti, Isabelle; Dessy, Francis J; Trofa, Andrew F; Schuind, Anne; Dubin, Gary

2009-10-01

This observer-blind study compared the prophylactic human papillomavirus (HPV) vaccines, Cervarix (GlaxoSmithKline) and Gardasil (Merck), by assessing immunogenicity and safety through one month after completion of the three-dose vaccination course. Women (n = 1106) were stratified by age (18-26, 27-35, 36-45 years) and randomized (1:1) to receive Cervarix (Months 0, 1, 6) or Gardasil (Months 0, 2, 6). At Month 7 after first vaccination, all women in the according-to-protocol cohort who were seronegative/DNA negative before vaccination for the HPV type analyzed had seroconverted for HPV-16 and HPV-18 serum neutralizing antibodies, as measured by pseudovirion-based neutralization assay (PBNA), except for two women aged 27-35 years in the Gardasil group who did not seroconvert for HPV-18 (98%). Geometric mean titers of serum neutralizing antibodies ranged from 2.3-4.8-fold higher for HPV-16 and 6.8-9.1-fold higher for HPV-18 after vaccination with Cervarix compared with Gardasil, across all age strata. In the total vaccinated cohort (all women who received at least one vaccine dose, regardless of their serological and DNA status prior to vaccination), Cervarix induced significantly higher serum neutralizing antibody titers in all age strata (p < 0.0001). Positivity rates for anti-HPV-16 and -18 neutralizing antibodies in cervicovaginal secretions and circulating HPV-16 and -18 specific memory B-cell frequencies were also higher after vaccination with Cervarix compared with Gardasil. Both vaccines were generally well tolerated. The incidence of unsolicited adverse events was comparable between vaccinated groups. The incidence of solicited symptoms was generally higher after Cervarix, injection site reactions being most common. However, compliance rates with the three-dose schedules were similarly high (>or= 84%) for both vaccines. Although the importance of differences in magnitude of immune response between these vaccines is unknown, they may represent determinants of duration of protection against HPV-16/18. Long-term studies evaluating duration of efficacy after vaccination are needed for both vaccines.

Ability to Maintain Internal Arousal and Motivation Modulates Brain Responses to Emotions

PubMed Central

Sterpenich, Virginie; Schwartz, Sophie; Maquet, Pierre; Desseilles, Martin

2014-01-01

Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression. PMID:25438046

Ability to maintain internal arousal and motivation modulates brain responses to emotions.

PubMed

Sterpenich, Virginie; Schwartz, Sophie; Maquet, Pierre; Desseilles, Martin

2014-01-01

Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression.

The pH and pCO2 dependence of sulfate reduction in shallow-sea hydrothermal CO2 – venting sediments (Milos Island, Greece)

PubMed Central

Bayraktarov, Elisa; Price, Roy E.; Ferdelman, Timothy G.; Finster, Kai

2013-01-01

Microbial sulfate reduction (SR) is a dominant process of organic matter mineralization in sulfate-rich anoxic environments at neutral pH. Recent studies have demonstrated SR in low pH environments, but investigations on the microbial activity at variable pH and CO2 partial pressure are still lacking. In this study, the effect of pH and pCO2 on microbial activity was investigated by incubation experiments with radioactive 35S targeting SR in sediments from the shallow-sea hydrothermal vent system of Milos, Greece, where pH is naturally decreased by CO2 release. Sediments differed in their physicochemical characteristics with distance from the main site of fluid discharge. Adjacent to the vent site (T ~40–75°C, pH ~5), maximal sulfate reduction rates (SRR) were observed between pH 5 and 6. SR in hydrothermally influenced sediments decreased at neutral pH. Sediments unaffected by hydrothermal venting (T ~26°C, pH ~8) expressed the highest SRR between pH 6 and 7. Further experiments investigating the effect of pCO2 on SR revealed a steep decrease in activity when the partial pressure increased from 2 to 3 bar. Findings suggest that sulfate reducing microbial communities associated with hydrothermal vent system are adapted to low pH and high CO2, while communities at control sites required a higher pH for optimal activity. PMID:23658555

The pH and pCO2 dependence of sulfate reduction in shallow-sea hydrothermal CO2 - venting sediments (Milos Island, Greece).

PubMed

Bayraktarov, Elisa; Price, Roy E; Ferdelman, Timothy G; Finster, Kai

2013-01-01

Microbial sulfate reduction (SR) is a dominant process of organic matter mineralization in sulfate-rich anoxic environments at neutral pH. Recent studies have demonstrated SR in low pH environments, but investigations on the microbial activity at variable pH and CO2 partial pressure are still lacking. In this study, the effect of pH and pCO2 on microbial activity was investigated by incubation experiments with radioactive (35)S targeting SR in sediments from the shallow-sea hydrothermal vent system of Milos, Greece, where pH is naturally decreased by CO2 release. Sediments differed in their physicochemical characteristics with distance from the main site of fluid discharge. Adjacent to the vent site (T ~40-75°C, pH ~5), maximal sulfate reduction rates (SRR) were observed between pH 5 and 6. SR in hydrothermally influenced sediments decreased at neutral pH. Sediments unaffected by hydrothermal venting (T ~26°C, pH ~8) expressed the highest SRR between pH 6 and 7. Further experiments investigating the effect of pCO2 on SR revealed a steep decrease in activity when the partial pressure increased from 2 to 3 bar. Findings suggest that sulfate reducing microbial communities associated with hydrothermal vent system are adapted to low pH and high CO2, while communities at control sites required a higher pH for optimal activity.

HIV-1 Autologous Antibody Neutralization Associates with Mother to Child Transmission

PubMed Central

Baan, Elly; de Ronde, Anthony; Stax, Martijn; Sanders, Rogier W.; Luchters, Stanley; Vyankandondera, Joseph; Lange, Joep M.; Pollakis, Georgios; Paxton, William A

2013-01-01

The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P  = 0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P  = 0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions. PMID:23874931

Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model.

PubMed

Karlsson, Ingrid; Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo; Stewart-Jones, Guillaume; Scarlatti, Gabriella; Fomsgaard, Anders

2017-11-17

The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone, and DNA prime with protein boost. The rabbit sera were screened for ADCC activity using a GranToxiLux-based assay with human peripheral blood mononuclear cells as effector cells and CEM.NKR CCR5 cells coated with HIV-1 envelope as target cells. The groups with the highest ADCC activity were further characterized for cross-reactivity between HIV-1 subtypes. The immunogen inducing the most potent and broadest ADCC response was a trimeric gp140. The ADCC activity was highest against the HIV-1 subtype corresponding to the immunogen. The ADCC activity did not necessarily reflect neutralizing activity in the pseudovirus-TZMbl assay, but there was an overall correlation between the two antiviral activities. We present a rabbit vaccination model and an assay suitable for screening HIV-1 vaccine candidates for the induction of ADCC-mediating antibodies in addition to neutralizing antibodies. The antigens and/or immunization strategies capable of inducing antibodies with ADCC activity did not necessarily induce neutralizing activity and vice versa. Nevertheless, we identified vaccine candidates that were able to concurrently induce both types of responses and that had ADCC activity that was cross-reactive between different subtypes. When searching for an effective vaccine candidate, it is important to evaluate the antibody response using a model and an assay measuring the desired function.

Solar Flare Prediction Model with Three Machine-learning Algorithms using Ultraviolet Brightening and Vector Magnetograms

NASA Astrophysics Data System (ADS)

Nishizuka, N.; Sugiura, K.; Kubo, Y.; Den, M.; Watari, S.; Ishii, M.

2017-02-01

We developed a flare prediction model using machine learning, which is optimized to predict the maximum class of flares occurring in the following 24 hr. Machine learning is used to devise algorithms that can learn from and make decisions on a huge amount of data. We used solar observation data during the period 2010-2015, such as vector magnetograms, ultraviolet (UV) emission, and soft X-ray emission taken by the Solar Dynamics Observatory and the Geostationary Operational Environmental Satellite. We detected active regions (ARs) from the full-disk magnetogram, from which ˜60 features were extracted with their time differentials, including magnetic neutral lines, the current helicity, the UV brightening, and the flare history. After standardizing the feature database, we fully shuffled and randomly separated it into two for training and testing. To investigate which algorithm is best for flare prediction, we compared three machine-learning algorithms: the support vector machine, k-nearest neighbors (k-NN), and extremely randomized trees. The prediction score, the true skill statistic, was higher than 0.9 with a fully shuffled data set, which is higher than that for human forecasts. It was found that k-NN has the highest performance among the three algorithms. The ranking of the feature importance showed that previous flare activity is most effective, followed by the length of magnetic neutral lines, the unsigned magnetic flux, the area of UV brightening, and the time differentials of features over 24 hr, all of which are strongly correlated with the flux emergence dynamics in an AR.

Pozzolanic filtration/solidification of radionuclides in nuclear reactor cooling water

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

Englehardt, J.D.; Peng, C.

1995-12-31

Laboratory studies to investigate the feasibility of one- and two-step processes for precipitation/coprecipitating radionuclides from nuclear reactor cooling water, filtering with pozzolanic filter aid, and solidifying, are reported in this paper. In the one-step process, ferrocyanide salt and excess lime are added ahead of the filter, and the resulting filter cake solidifies by a pozzolanic reaction. The two-step process involves addition of solidifying agents subsequent to filtration. It was found that high surface area diatomaceous synthetic calcium silicate powders, sold commercially as functional fillers and carriers, adsorb nickel isotopes from solution at neutral and slightly basic pH. Addition of themore » silicates to cooling water allowed removal of the tested metal isotopes (nickel, iron, manganese, cobalt, and cesium) simultaneously at neutral to slightly basic pH. Lime to diatomite ratio was the most influential characteristic of composition on final strength tested, with higher lime ratios giving higher strength. Diatomaceous earth filter aids manufactured without sodium fluxes exhibited higher pozzolanic activity. Pozzolanic filter cake solidified with sodium silicate and a ratio of 0.45 parts lime to 1 part diatomite had compressive strength ranging from 470 to 595 psi at a 90% confidence level. Leachability indices of all tested metals in the solidified waste were acceptable. In light of the typical requirement of removing iron and desirability of control over process pH, a two-step process involving addition of Portland cement to the filter cake may be most generally applicable.« less

Fast-ion transport in low density L-mode plasmas at TCV using FIDA spectroscopy and the TRANSP code

NASA Astrophysics Data System (ADS)

Geiger, B.; Karpushov, A. N.; Duval, B. P.; Marini, C.; Sauter, O.; Andrebe, Y.; Testa, D.; Marascheck, M.; Salewski, M.; Schneider, P. A.; the TCV Team; the EUROfusion MST1 Team

2017-11-01

Experiments with the new neutral beam injection source of TCV have been performed with high fast-ion fractions (>20%) that exhibit a clear reduction of the loop voltage and a clear increase of the plasma pressure in on- and off-axis heating configurations. However, good quantitative agreement between the experimental data and TRANSP predictions is only found when including strong additional fast-ion losses. These losses could in part be caused by turbulence or MHD activity as, e.g. high frequency modes near the frequency of toroidicity induced Alfvén eignmodes are observed. In addition, a newly installed fast-ion D-alpha (FIDA) spectroscopy system measures strong passive radiation and, hence, indicates the presence of high background neutral densities such that charge-exchange losses are substantial. Also the active radiation measured with the FIDA diagnostic, as well as data from a neutral particle analyzer, suggest strong fast-ion losses and large neutral densities. The large neutral densities can be justified since high electron temperatures (3-4 keV), combined with low electron densities (about 2× {10}19 m-3) yield long mean free paths of the neutrals which are penetrating from the walls.

Intestinal Immune Responses to Type 2 Oral Polio Vaccine (OPV) Challenge in Infants Previously Immunized With Bivalent OPV and Either High-Dose or Standard Inactivated Polio Vaccine.

PubMed

Brickley, Elizabeth B; Strauch, Carolyn B; Wieland-Alter, Wendy F; Connor, Ruth I; Lin, Shu; Weiner, Joshua A; Ackerman, Margaret E; Arita, Minetaro; Oberste, M Steven; Weldon, William C; Sáez-Llorens, Xavier; Bandyopadhyay, Ananda S; Wright, Peter F

2018-01-17

The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood. In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2-specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants' intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples. Despite mIPV2HD's 4-fold higher type 2 polio D-antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants' intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2-specific IgA responses and stool neutralization were observed by 2 weeks after challenge. Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge. NCT02111135. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

Immunological correlates for protection against intranasal challenge of Bacillus anthracis spores conferred by a protective antigen-based vaccine in rabbits.

PubMed

Weiss, Shay; Kobiler, David; Levy, Haim; Marcus, Hadar; Pass, Avi; Rothschild, Nili; Altboum, Zeev

2006-01-01

Correlates between immunological parameters and protection against Bacillus anthracis infection in animals vaccinated with protective antigen (PA)-based vaccines could provide surrogate markers to evaluate the putative protective efficiency of immunization in humans. In previous studies we demonstrated that neutralizing antibody levels serve as correlates for protection in guinea pigs (S. Reuveny et al., Infect. Immun. 69:2888-2893, 2001; H. Marcus et al., Infect. Immun. 72:3471-3477, 2004). In this study we evaluated similar correlates for protection by active and passive immunization of New Zealand White rabbits. Full immunization and partial immunization were achieved by single and multiple injections of standard and diluted doses of a PA-based vaccine. Passive immunization was carried out by injection of immune sera from rabbits vaccinated with PA-based vaccine prior to challenge with B. anthracis spores. Immunized rabbits were challenged by intranasal spore instillation with one of two virulent strains (strains Vollum and ATCC 6605). The immune competence was estimated by measuring the level of total anti-PA antibodies, the neutralizing antibody titers, and the conferred protective immunity. The results indicate that total anti-PA antibody titers greater than 1 x 10(5) conferred protection, whereas lower titers (between 10(4) and 10(5)) provided partial protection but failed to predict protection. Neutralizing antibody titers between 500 and 800 provided partial protection, while titers higher than 1,000 conferred protection. In conclusion, this study emphasizes that regardless of the immunization regimen or the time of challenge, neutralizing antibody titers are better predictors of protection than total anti-PA titers.

Intestinal Immune Responses to Type 2 Oral Polio Vaccine (OPV) Challenge in Infants Previously Immunized With Bivalent OPV and Either High-Dose or Standard Inactivated Polio Vaccine

PubMed Central

Brickley, Elizabeth B; Strauch, Carolyn B; Wieland-Alter, Wendy F; Connor, Ruth I; Lin, Shu; Weiner, Joshua A; Ackerman, Margaret E; Arita, Minetaro; Oberste, M Steven; Weldon, William C; Sáez-Llorens, Xavier; Bandyopadhyay, Ananda S; Wright, Peter F

2018-01-01

Abstract Background The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood. Methods In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2–specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants’ intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples. Results Despite mIPV2HD’s 4-fold higher type 2 polio D–antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants’ intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2–specific IgA responses and stool neutralization were observed by 2 weeks after challenge. Conclusions Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge. Clinical Trials Registration NCT02111135. PMID:29304199

Complex Contexts: Women and Community-Higher-Education in Ireland

ERIC Educational Resources Information Center

Quilty, Aideen; McAuliffe, Mary; Barry, Ursula

2016-01-01

Education is not a neutral process, it can be used to establish and maintain conformity or be part of a process of liberation and social change (Freire, 1979; hooks, 1994). The Irish State's failure to acknowledge this lack of neutrality has characterised the formal education system in Ireland since its inception. From the introduction of the…

Variables influencing anti-human immunodeficiency virus type 1 neutralizing human monoclonal antibody (NhMAb) production among infected Thais.

PubMed

Akapirat, Siriwat; Avihingsanon, Anchalee; Ananworanich, Jintanat; Schuetz, Alexandra; Ramasoota, Pongrama; Luplertlop, Natthanej; Ono, Ken-Ichiro; Ikuta, Kazuyoshi; Utachee, Piraporn; Kameoka, Masanori; Leaungwutiwong, Pornsawan

2013-09-01

We conducted this study to determine the clinical variables associated with the production of human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 01_AE neutralizing human monoclonal antibodies (NhMAbs) using a hybridoma technique. This cross sectional study was performed in 20 asymptomatic HIV-1-infected Thais. Peripheral blood mononuclear cells (PBMCs) were obtained from each study participant and fused with SPYMEG cells. Culture supernatant collected from growing hybridomas was tested for neutralizing activity against HIV-1 CRF01_AE Env-recombinant viruses. Fifty hybridomas expressing anti-HIV-1 NhMAbs with strong neutralizing activity against at least 1 CRF01_AE Env-recombinant virus were found. A positive association between the numbers of hybridomas produced and the CD4 counts of study participants (p = 0.019) was observed. NhMAb-producing hybridomas with strong neutralizing activity were mostly found in participans diagnosed with HIV-1 infection within the previous 1 year. The HIV-1 viral load was not significantly correlated with the numbers of either established hybridomas or clones expressing anti-HIV-1 NhMAbs with strong neutralizing activity. To our knowledge, this is the first study of NhMAb-producing hybridomas obtained from HIV-1 CRF01_AE-infected populations identified by antibody binding to HIV-1 V3 loop peptide enzyme-linked immunosorbent assay (ELISA) or TRUGENE HIV-1 Genotyping Assay (HIV-1 pol sequence). It provides important criterion to slect study participants with high CD4 counts who produce large numbers of hybridoma clones. The results are valuable for further studies related to nurtalizing antibodies production and HIV-1 vaccine development.

Children prenatally exposed to maternal anxiety devote more attentional resources to neutral pictures.

PubMed

van den Heuvel, Marion I; Henrichs, Jens; Donkers, Franc C L; Van den Bergh, Bea R H

2017-10-22

Maternal anxiety during pregnancy can negatively affect fetal neurodevelopment, predisposing the offspring to a higher risk of behavioral and emotional problems later in life. The current study investigates the association between maternal anxiety during pregnancy and child affective picture processing using event-related brain potentials (ERPs). Mothers reported anxiety during the second trimester using the anxiety subscale of the Symptom Checklist (SCL-90). At age 4 years, child affective picture processing (N = 86) was measured by recording ERPs during viewing of neutral, pleasant, and unpleasant pictures selected from the International Affective Pictures System. The late positive potential (LPP)-an ERP component reflecting individual differences in affective processing-was used as child outcome. The expected positive association between maternal anxiety and LPP amplitude for unpleasant pictures was not found. Nevertheless, we found a positive association between maternal anxiety during pregnancy and LPP amplitudes for neutral pictures in the middle and late time window at anterior locations (all p < .05). These associations remained significant after adjusting for maternal postnatal anxiety and gestational age at birth and after FDR correction for multiple comparisons. Our study provides neurophysiological evidence that children prenatally exposed to higher maternal anxiety devote more attentional resources to neutral pictures, but not to unpleasant pictures. Possibly, these children show enhanced vigilance for threat when viewing neutral pictures. Although useful in dangerous environments, this enhanced vigilance may predispose children prenatally exposed to higher maternal anxiety to developing behavioral and/or emotional problems later in life. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=kEzYi6IS2HA. © 2017 John Wiley & Sons Ltd.

Physiological and neural correlates of worry and rumination: Support for the contrast avoidance model of worry.

PubMed

Steinfurth, Elisa C K; Alius, Manuela G; Wendt, Julia; Hamm, Alfons O

2017-02-01

The current experiments tested neural and physiological correlates of worry and rumination in comparison to thinking about neutral events. According to the avoidance model-stating that worry is a strategy to reduce intense emotions-physiological and neurobiological activity during worried thinking should not differ from activation during neutral thinking. According to the contrast avoidance model-stating that worry is a strategy to reduce abrupt shifts of emotions-activity should be increased. To test these competing models, we induced worry and neutral thinking in healthy participants using personal topics. A rumination condition was added to investigate the specificity of changes induced by the mental process. Two experiments were conducted assessing the effects on different response levels: (1) neural activation using fMRI, and (2) physiological response mobilization using startle and autonomic measures. During worry, participants showed a potentiated startle response and BOLD activity indicative of emotional network activation. These data partly support the contrast avoidance model of worry. Both mental processes showed elevated activity in a common network referred to as default network indicating self-referential activity. © 2016 Society for Psychophysiological Research.

High-intensity erotic visual stimuli de-activate the primary visual cortex in women.

PubMed

Huynh, Hieu K; Beers, Caroline; Willemsen, Antoon; Lont, Erna; Laan, Ellen; Dierckx, Rudi; Jansen, Monique; Sand, Michael; Weijmar Schultz, Willibrord; Holstege, Gert

2012-06-01

The primary visual cortex, Brodmann's area (BA 17), plays a vital role in basic survival mechanisms in humans. In most neuro-imaging studies in which the volunteers have to watch pictures or movies, the primary visual cortex is similarly activated independent of the content of the pictures or movies. However, in case the volunteers perform demanding non-visual tasks, the primary visual cortex becomes de-activated, although the amount of incoming visual sensory information is the same. Do low- and high-intensity erotic movies, compared to neutral movies, produce similar de-activation of the primary visual cortex? Brain activation/de-activation was studied by Positron Emission Tomography scanning of the brains of 12 healthy heterosexual premenopausal women, aged 18-47, who watched neutral, low- and high-intensity erotic film segments. We measured differences in regional cerebral blood flow (rCBF) in the primary visual cortex during watching neutral, low-intensity erotic, and high-intensity erotic film segments. Watching high-intensity erotic, but not low-intensity erotic movies, compared to neutral movies resulted in strong de-activation of the primary (BA 17) and adjoining parts of the secondary visual cortex. The strong de-activation during watching high-intensity erotic film might represent compensation for the increased blood supply in the brain regions involved in sexual arousal, also because high-intensity erotic movies do not require precise scanning of the visual field, because the impact is clear to the observer. © 2012 International Society for Sexual Medicine.

A defucosylated bispecific multivalent molecule exhibits broad HIV-1 neutralizing activity and enhanced ADCC against reactivated HIV-1 latently infected cells.

PubMed

Kong, Desheng; Wang, Yan; Ji, Ping; Li, Wei; Ying, Tianlei; Huang, Jinghe; Wang, Chen; Wu, Yanling; Wang, Yanping; Chen, Weizao; Hao, Yanling; Hong, Kunxue; Shao, Yiming; Dimitrov, Dimiter S; Jiang, Shibo; Ma, Liying

2018-05-11

Current treatments cannot completely eradicate HIV-1 owing to the presence of latently infected cells which harbor transcriptionally silent HIV-1. However, defucosylated antibodies can readily kill latently infected cells after their activation to express envelope glycoprotein (Env) through antibody-dependent cellular cytotoxicity (ADCC). We herein aimed to test a defucosylated bispecific multivalent molecule consisting of domain-antibody and single-domain CD4, LSEVh-LS-F, for its HIV-1 neutralizing activity and ADCC against the reactivated latently infected cells, compared with the non-defucosylated molecule LSEVh-LS. LSEVh-LS-F's neutralizing activity against a panel of newly characterized Chinese HIV-1 clinical isolates was assessed by using TZM-bl- and PBMC-based assays. LSEVh-LS-F-mediated ADCC in the presence of NK cells against cell lines that stably express Env proteins, HIV-1-infected cells and LRA-reactivated HIV-1 latent cells, was measured using a lactate dehydrogenase (LDH) cytotoxicity assay or flow cytometry. LSEVh-LS-F and LSEVh-LS were equally effective in neutralized infection of all HIV-1 isolates tested with IC50 and IC90 values 3∼4-fold lower than those of VRC01. LSEVh-LS-F was more effective in NK-mediated killing of HIV-1 Env-expressing cell lines, HIV-1-infected cells, latency reactivation agents-reactivated ACH2 cells, and reactivated latently infected resting CD4 T cell line as well as resting CD4 T lymphocytes isolated from patients receiving highly active anti-retroviral therapy (HAART). LSEVh-LS-F exhibits broad HIV-1 neutralizing activity and enhanced ADCC against HIV-1-infected cells, reactivated latently infected cell lines and primary CD4 T cells, thus being a promising candidate therapeutic for eradicating the HIV-1 reservoir.

The perception of emotion-free faces in schizophrenia: a magneto-encephalography study.

PubMed

López-Ibor, Juan J; López-Ibor, María-Inés; Méndez, María-Andreína; Morón, María-Dolores; Ortiz-Terán, Laura; Fernandez, Alberto; Diaz-Marsá, Marina; Ortiz, Tomás

2008-01-01

To analyze how patients suffering from schizophrenia perceive faces of unknown individuals that show no actual emotions in order to investigate the attribution of meanings to a relatively non-significant but complex sensory experience. Analysis of baseline and poststimulation magneto-encephalographic recordings. The stimuli consisted of four pictures with neutral emotional expression of male and female faces of Spanish individuals unknown to research subjects. Twelve right-handed patients suffering from schizophrenia (DSM IV-TR criteria), age 18-65, with active delusional activity (SAPS score in delusions above 39) and 15 right-handed sex- and age-matched control subjects. Compared to controls patients have a significant higher activity of both hemispheres (0-700 ms) being the activity in the right hemisphere (RH) higher than in the left hemisphere (LH). Patients also have a higher activity on the middle fusiform gyrus (BA 37) in the LH (200-300 ms), on the superior temporal areas (BA 22, 41 and 42) in both hemispheres (100-700 ms) and on the temporal pole (BA 38) in the RH (300-400 ms) and a lower activity in the LH of the latter. The areas that are more activated in our study are those involved in the process of thinking, in attributing meanings to perceptions and in activities such as theory of mind, which are essential for social interaction. The anterior temporal areas less activated indicate a reduced semantic memory for faces that could explain the social withdrawal of schizophrenia. These alterations are suggestive of a dysfunction of left hemisphere neuronal networks.

Auroral origin of medium scale gravity waves in neutral composition and temperature

NASA Technical Reports Server (NTRS)

Chandra, S.; Spencer, N. W.; Krankowsky, D.; Laemmerzahl, P.

1979-01-01

The kinetic temperature and neutral composition data obtained from the Aeros B neutral atmosphere temperature experiment and the neutral and ion mass spectrometer show spatial structures characteristic of medium scale gravity waves with a wavelength in the range of several hundred kilometers. These waves are associated with auroral activity, and their spatial structure reflects the time history of the auroral electrojet. The medium scale gravity waves tend to propagate to mid-latitudes on the nightside. On the dayside their range is limited to high latitudes. Gravity waves are carriers of auroral energy to middle and low latitudes where they may cause irreversible changes in temperature via viscous dissipation. Since auroral activity occurs frequently, it is suggested that this energy reaches the mid-latitude region of the thermosphere much more frequently than is indicated by planetary magnetic indices.

Antibodies against neutralization epitopes of human cytomegalovirus gH/gL/pUL128-130-131 complex and virus spreading may correlate with virus control in vivo.

PubMed

Lilleri, Daniele; Kabanova, Anna; Lanzavecchia, Antonio; Gerna, Giuseppe

2012-12-01

Recently, human cytomegalovirus (HCMV) UL128-131 locus gene products have been found to be associated with glycoprotein H (gH) and glycoprotein L (gL) to form a pentameric glycoprotein complex gH/gL/pUL128-130-131, which is present in the virus envelope and elicits production of neutralizing antibodies. Purpose of this study was to verify whether in vitro activities of these antibodies may correlate with protection in vivo. By using potently neutralizing human monoclonal antibodies (mAbs) targeting 10 different epitopes of the pentameric complex, a competitive ELISA assay was developed, in which the pentamer bound to the solid-phase was reacted competitively with human sera and murinized human mAbs. In addition, inhibition of virus spreading (plaque formation and leukocyte transfer) by neutralizing human mAbs and sera was investigated. In the absence of any reactivity of sera from HCMV-seronegative subjects, antibodies to all 10 epitopes were detected in HCMV-seropositive individuals. During primary HCMV infection in pregnancy antibodies to some epitopes showed a trend towards an earlier appearance in mothers not transmitting the virus to the fetus as compared to transmitting mothers. In addition, the activity of neutralizing human mAbs and sera in blocking virus cell-to-cell spreading and virus transfer to leukocytes from infected endothelial cells was shown to develop during the convalescent phase of primary infection. Dissection of the neutralizing/inhibiting activities of human sera may be helpful in the study of their protective role in vivo. In particular, neutralizing antibodies to the pentamer may be a surrogate marker of protection in vivo.

Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody: epitope definition and implications in risk stratification of patients under natalizumab therapy.

PubMed

Diotti, Roberta Antonia; Mancini, Nicasio; Clementi, Nicola; Sautto, Giuseppe; Moreno, Guisella Janett; Criscuolo, Elena; Cappelletti, Francesca; Man, Petr; Forest, Eric; Remy, Louise; Giannecchini, Simone; Clementi, Massimo; Burioni, Roberto

2014-08-01

JC virus (JCPyV) has gained novel clinical importance as cause of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease recently associated to immunomodulatory drugs, such as natalizumab used in multiple sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and this makes the need of PML risk stratification among natalizumab-treated patients very compelling. Clinical and laboratory-based risk-stratification markers have been proposed, one of these is represented by the JCPyV-seropositive status, which includes about 54% of MS patients. We recently proposed to investigate the possible protective role of neutralizing humoral immune response in preventing JCPyV reactivation. In this proof-of-concept study, by cloning the first human monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1, we optimized a robust anti-JCPyV neutralization assay. This allowed us to evaluate the neutralizing activity in JCPyV-positive sera from MS patients, demonstrating the lack of correlation between the level of anti-JCPyV antibody and anti-JCPyV neutralizing activity. Relevant consequences may derive from future clinical studies induced by these findings; indeed the study of the serum anti-JCPyV neutralizing activity could allow not only a better risk stratification of the patients during natalizumab treatment, but also a better understanding of the pathophysiological mechanisms leading to PML, highlighting the contribution of peripheral versus central nervous system JCPyV reactivation. Noteworthy, the availability of GRE1 could allow the design of novel immunoprophylactic strategies during the immunomodulatory treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

A single amino-acid change in a highly conserved motif of gp41 elicits HIV-1 neutralization and protects against CD4 depletion.

PubMed

Petitdemange, Caroline; Achour, Abla; Dispinseri, Stefania; Malet, Isabelle; Sennepin, Alexis; Ho Tsong Fang, Raphaël; Crouzet, Joël; Marcelin, Anne-Geneviève; Calvez, Vincent; Scarlatti, Gabriella; Debré, Patrice; Vieillard, Vincent

2013-09-01

The induction of neutralizing antibodies against conserved regions of the human immunodeficiency virus type 1 (HIV-1) envelope protein is a major goal of vaccine strategies. We previously identified 3S, a critical conserved motif of gp41 that induces the NKp44L ligand of an activating NK receptor. In vivo, anti-3S antibodies protect against the natural killer (NK) cell-mediated CD4 depletion that occurs without efficient viral neutralization. Specific substitutions within the 3S peptide motif were prepared by directed mutagenesis. Virus production was monitored by measuring the p24 production. Neutralization assays were performed with immune-purified antibodies from immunized mice and a cohort of HIV-infected patients. Expression of NKp44L on CD4(+) T cells and degranulation assay on activating NK cells were both performed by flow cytometry. Here, we show that specific substitutions in the 3S motif reduce viral infection without affecting gp41 production, while decreasing both its capacity to induce NKp44L expression on CD4(+) T cells and its sensitivity to autologous NK cells. Generation of antibodies in mice against the W614 specific position in the 3S motif elicited a capacity to neutralize cross-clade viruses, notable in its magnitude, breadth, and durability. Antibodies against this 3S variant were also detected in sera from some HIV-1-infected patients, demonstrating both neutralization activity and protection against CD4 depletion. These findings suggest that a specific substitution in a 3S-based immunogen might allow the generation of specific antibodies, providing a foundation for a rational vaccine that combine a capacity to neutralize HIV-1 and to protect CD4(+) T cells.

Neck muscle activation and head postures in common high performance aerial combat maneuvers.

PubMed

Netto, Kevin J; Burnett, Angus F

2006-10-01

Neck injuries are common in high performance combat pilots and have been attributed to high gravitational forces and the non-neutral head postures adopted during aerial combat maneuvers. There is still little known about the pathomechanics of these injuries. Six Royal Australian Air Force Hawk pilots flew a sortie that included combinations of three +Gz levels (1, 3, and 5) and four head postures (Neutral, Turn, Extension, and Check-6). Surface electromyography from neck and shoulder muscles was recorded in flight. Three-dimensional measures of head postures adopted in flight were estimated postflight with respect to end-range of the cervical spine using an electromagnetic tracking device. Mean muscle activation increased significantly with both increasing +Gz and non-neutral head postures. Check-6 at +5 Gz (mean activation of all muscles = 51% MVIC) elicited significantly greater muscle activation in most muscles when compared with Neutral, Extension, and Turn head postures. High levels of muscle co-contraction were evident in high acceleration and non-neutral head postures. Head kinematics showed Check-6 was closest to end-range in any movement plane (86% ROM in rotation) and produced the greatest magnitude of rotation in other planes. Turn and Extension showed a large magnitude of rotation with reference to end-range in the primary plane of motion but displayed smaller rotations in other planes. High levels of neck muscle activation and co-contraction due to high +Gz and head postures close to end range were evident in this study, suggesting the major influence of these factors on the pathomechanics of neck injuries in high performance combat pilots.

Capacitive Neutralization Dialysis for Direct Energy Generation.

PubMed

Liu, Yue; Zhang, Yi; Ou-Yang, Wei; Bastos Sales, Bruno; Sun, Zhuo; Liu, Fei; Zhao, Ran

2017-08-15

Capacitive neutralization dialysis energy (CNDE) is proposed as a novel energy-harvesting technique that is able to utilize waste acid and alkaline solutions to produce electrical energy. CNDE is a modification based on neutralization dialysis. It was found that a higher NaCl concentration led to a higher open-circuit potential when the concentrations of acid and alkaline solutions were fixed. Upon closing of the circuit, the membrane potential was used as a driving force to move counter ions into the electrical double layers at the electrode-liquid interface, thereby creating an ionic current. Correspondingly, in the external circuit, electrons flow through an external resistor from one electrode to the other, thereby generating electrical energy directly. The influence of external resistances was studied to achieve greater energy extraction, with the maximum output of 110 mW/m 2 obtained by employing an external resistance of 5 Ω together with the AC-coated electrode.

Preliminary measurements of plasma fluctuations in an 8-cm mercury ion thruster

NASA Technical Reports Server (NTRS)

Serafini, J. S.; Nakanishi, S.

1975-01-01

The rms magnitude, spectra, and cross correlations for the fluctuations in the beam current, the neutralizer keeper current, and the discharge current and voltage were measured for an 8-cm diameter, dished grid ion thruster for a beam current of 72 milliamps. The ratio of the rms magnitude of the fluctuations to the time-mean neutralizer keeper current was found to depend significantly on the neutralizer time-mean keeper current, the flow rate, and keeper hold diameter. The maxima of the spectra of the beam current fluctuations did not depend on the discharge fluctuations. It was found that: (1) the discharge current fluctuations do not directly contribute to the beam current fluctuations; and (2) the neutralizer contributions to the beam fluctuations are small (for good neutralizer-to-beam coupling) but not negligible and appear mostly in the higher frequency range measured.

Energy neutral protocol based on hierarchical routing techniques for energy harvesting wireless sensor network

NASA Astrophysics Data System (ADS)

Muhammad, Umar B.; Ezugwu, Absalom E.; Ofem, Paulinus O.; Rajamäki, Jyri; Aderemi, Adewumi O.

2017-06-01

Recently, researchers in the field of wireless sensor networks have resorted to energy harvesting techniques that allows energy to be harvested from the ambient environment to power sensor nodes. Using such Energy harvesting techniques together with proper routing protocols, an Energy Neutral state can be achieved so that sensor nodes can run perpetually. In this paper, we propose an Energy Neutral LEACH routing protocol which is an extension to the traditional LEACH protocol. The goal of the proposed protocol is to use Gateway node in each cluster so as to reduce the data transmission ranges of cluster head nodes. Simulation results show that the proposed routing protocol achieves a higher throughput and ensure the energy neutral status of the entire network.

Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

PubMed Central

Schanz, Merle; Reynell, Lucy; Günthard, Huldrych F.; Rusert, Peter; Trkola, Alexandra

2012-01-01

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo. PMID:22496655

Costs of success: Financial implications of implementation of active learning in introductory physics courses for students and administrators

NASA Astrophysics Data System (ADS)

Brewe, Eric; Dou, Remy; Shand, Robert

2018-02-01

Although active learning is supported by strong evidence of efficacy in undergraduate science instruction, institutions of higher education have yet to embrace comprehensive change. Costs of transforming instruction are regularly cited as a key factor in not adopting active-learning instructional practices. Some cite that alternative methods to stadium-style, lecture-based education are not financially viable to an academic department. This paper examines that argument by presenting an ingredients approach to estimating costs of two instructional methods used in introductory university physics courses at a large public U.S. university. We use a metric common in educational economics, cost effectiveness (CE), which is the total cost per student passing the class. We then compare the CE of traditional, passive-learning lecture courses to those of a well-studied, active-learning curriculum (Modeling Instruction) as a way of evaluating the claim that active learning is cost prohibitive. Our findings are that the Modeling Instruction approach has a higher cost per passing student (MI = 1 ,030 /passing student vs Trad = 790 /passing student). These results are discussed from perspectives of university administrators, students, and taxpayers. We consider how MI would need to adapt in order to make the benefits of active learning (particularly higher pass rates and gains on multiple measured student outcomes) available in a cost-neutral setting. This approach aims to provide a methodology to better inform decision makers balancing financial, personnel, and curricular considerations.

Smelling chemosensory signals of males in anxious versus nonanxious condition increases state anxiety of female subjects.

PubMed

Albrecht, Jessica; Demmel, Maria; Schöpf, Veronika; Kleemann, Anna Maria; Kopietz, Rainer; May, Johanna; Schreder, Tatjana; Zernecke, Rebekka; Brückmann, Hartmut; Wiesmann, Martin

2011-01-01

The hypothesis of this experiment was that humans in an anxious state compared with a nonanxious state are able to increase anxiety levels in other humans via their body odors. Specifically, we hypothesized that male chemosensory anxiety signals compared with neutral chemosignals increase state anxiety of female subjects. Thirteen male subjects participated in 2 different sweat donation sessions: chemosignals were collected during participation in a high rope course (anxiety condition) and in an ergometer workout (neutral condition). State and trait anxiety were evaluated in 20 female odor recipients using Spielberger's state-trait anxiety inventory in a double-blind design. Comparison of state anxiety of odor donors between control and anxiety condition differed significantly indicating that our model of anxiety induction successfully led to the expected change in emotion. Comparison of state anxiety of odor recipients showed a trend toward higher state anxiety in the anxiety condition compared with the neutral condition after 5 min of odor exposure. After 20 min of odor exposure, state anxiety of female subjects was significantly higher during the perception of sweat collected during the anxiety condition in comparison with the perception of sweat collected during the neutral condition. This experiment gives evidence that male anxiety chemosignals compared with neutral chemosignals are capable of inducing an increased state anxiety in female subjects.

Cytomegalovirus neutralization by hyperimmune and standard intravenous immunoglobulin preparations.

PubMed

Planitzer, Christina B; Saemann, Marcus D; Gajek, Hartwig; Farcet, Maria R; Kreil, Thomas R

2011-08-15

Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests. CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations. Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations. The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

Investigations on the effect of flavonoids from banana, Musa paradisiaca L. on lipid metabolism in rats.

PubMed

Vijayakumar, S; Presannakumar, G; Vijayalakshmi, N R

2009-01-01

Oral administration of flavonoids extracted from unripe fruits of Musa paradisiaca showed significant hypolipidemic activities in male rats (Sprague Dawley strain) at a dose of 1 mg/100 g body weight (BW)/day. Concentrations of cholesterol, phospholipids, free fatty acids, and triglycerides showed significant decrease in the serum, liver, kidney, and brain of experimental animals. HMG CoA reductase activity was found to be enhanced, while activities of glucose-6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Activities of lipoprotein lipase and plasma LCAT showed significant enhancement. A significant increase in the concentrations of hepatic and fecal bile acids and fecal neutral sterols was also observed indicating a higher rate of degradation of cholesterol. The present study indicates that although there is an increase in the rate of synthesis of cholesterol in the liver, the process of degradation exceeds the rate of synthesis.

Neutral degradates of chloroacetamide herbicides: occurrence in drinking water and removal during conventional water treatment.

PubMed

Hladik, Michelle L; Bouwer, Edward J; Roberts, A Lynn

2008-12-01

Treated drinking water samples from 12 water utilities in the Midwestern United States were collected during Fall 2003 and Spring 2004 and were analyzed for selected neutral degradates of chloroacetamide herbicides, along with related compounds. Target analytes included 20 neutral chloroacetamide degradates, six ionic chloroacetamide degradates, four parent chloroacetamide herbicides, three triazine herbicides, and two neutral triazine degradates. In the fall samples, 17 of 20 neutral chloroacetamide degradates were detected in the finished drinking water, while 19 of 20 neutral chloroacetamide degradates were detected in the spring. Median concentrations for the neutral chloroacetamide degradates were approximately 2-60ng/L during both sampling periods. Concentrations measured in the fall samples of treated water were nearly the same as those measured in source waters, despite the variety of treatment trains employed. Significant removals (average of 40% for all compounds) were only found in the spring samples at those utilities that employed activated carbon.

Can policy ameliorate socioeconomic inequities in obesity and obesity-related behaviours? A systematic review of the impact of universal policies on adults and children.

PubMed

Olstad, D L; Teychenne, M; Minaker, L M; Taber, D R; Raine, K D; Nykiforuk, C I J; Ball, K

2016-12-01

This systematic review examined the impact of universal policies on socioeconomic inequities in obesity, dietary and physical activity behaviours among adults and children. PRISMA-Equity guidelines were followed. Database searches spanned from 2004 to August 2015. Eligible studies assessed the impact of universal policies on anthropometric, dietary or physical activity-related outcomes in adults or children according to socioeconomic position. Thirty-six studies were included. Policies were classified as agentic, agento-structural or structural, and their impact on inequities was rated as positive, neutral, negative or mixed according to the dominant associations observed. Most policies had neutral impacts on obesity-related inequities regardless of whether they were agentic (60% neutral), agento-structural (68% neutral) or structural (67% neutral). The proportion of positive impacts was similar across policy types (10% agentic, 18% agento-structural and 11% structural), with some differences for negative impacts (30% agentic, 14% agento-structural and 22% structural). The majority of associations remained neutral when stratified by participant population, implementation level and socioeconomic position measures and by anthropometric and behavioural outcomes. Fiscal measures had consistently neutral or positive impacts on inequities. Findings suggest an important role for policy in addressing obesity in an equitable manner and strengthen the case for implementing a broad complement of policies spanning the agency-structure continuum. © 2016 World Obesity Federation.

Evaluation of smallpox vaccines using variola neutralization.

PubMed

Damon, Inger K; Davidson, Whitni B; Hughes, Christine M; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Frey, Sharon E; Newman, Frances; Belshe, Robert B; Yan, Lihan; Karem, Kevin

2009-08-01

The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

Disentangling the roles of arousal and amygdala activation in emotional declarative memory

PubMed Central

Fernández, Guillén; Hermans, Erno J.

2016-01-01

A large body of evidence in animals and humans implicates the amygdala in promoting memory for arousing experiences. Although the amygdala can trigger threat-related noradrenergic-sympathetic arousal, in humans amygdala activation and noradrenergic-sympathetic arousal do not always concur. This raises the question how these two processes play a role in enhancing emotional declarative memory. This study was designed to disentangle these processes in a combined subsequent-memory/fear-conditioning paradigm with neutral items belonging to two conceptual categories as conditioned stimuli. Functional MRI, skin conductance (index of sympathetic activity), and pupil dilation (indirect index of central noradrenergic activity) were acquired throughout procedures. Recognition memory for individual items was tested 24 h later. We found that pupil dilation and skin conductance responses were higher on CS+ (associated with a shock) compared with CS− trials, irrespective of later memory for those items. By contrast, amygdala activity was only higher for CS+ items that were later confidently remembered compared with CS+ items that were later forgotten. Thus, amygdala activity and not noradrenergic-sympathetic arousal, predicted enhanced declarative item memory. This dissociation is in line with animal models stating that the amygdala integrates arousal-related neuromodulatory changes to alter mnemonic processes elsewhere in the brain. PMID:27217115

Research and development at the Marshall Space Flight Center Neutral Buoyancy Simulator

NASA Technical Reports Server (NTRS)

Kulpa, Vygantas P.

1987-01-01

The Neutral Buoyancy Simulator (NBS), a facility designed to imitate zero-gravity conditions, was used to test the Experimental Assembly of Structures in Extravehicular Activity (EASE) and the Assembly Concept for Construction of Erectable Space Structures (ACCESS). Neutral Buoyancy Simulator applications and operations; early space structure research; development of the EASE/ACCESS experiments; and improvement of NBS simulation are summarized.

Statistical Relationships between the El Niño Southern Oscillation, the North Atlantic Oscillation, and Winter Tornado Outbreaks in the U.S

NASA Astrophysics Data System (ADS)

Robinson Cook, A. D.; Schaefer, J. T.

2009-12-01

Winter tornado activity (January-March) between 1950 and 2003 was analyzed to determine the possible effects of the El Niño Southern Oscillation and the North Atlantic Oscillation on the frequency, location, and strength of tornado outbreaks in the United States. Outbreaks were gauged through analyses of tornadoes occurring on tornado days (a calendar day featuring six or more tornadoes within the contiguous United States) and then stratified according to warm (37 tornado days), cold (51 tornado days), and neutral (74 tornado days) winter ENSO phase. Tornado days were also stratified according to NAO phase (positive, negative, and neutral) as well. Although significant changes in the frequency of tornado outbreaks were not observed, spatial shifts in tornado activity are observed, primarily as a function of ENSO phase. Historically, the neutral ENSO phase features tornado outbreaks from central Oklahoma and Kansas eastward through the Carolinas. During cold ENSO phases (La Niña), tornado outbreaks typically occur in a zone stretching from southeastern Texas northeastward into Illinois, Indiana, and Michigan. Winter tornado activity was mainly limited to areas near the Gulf Coast, including central Florida, during anomalously warm phases (El Niño). Shifts in the intensity of tornado activity were also found as a function of ENSO and particularly NAO phase. Stronger tornadoes with longer path lengths were observed during La Niña and Neutral ENSO events, as well as Positive and Neutral NAO events.

Facial expression primes and implicit regulation of negative emotion.

PubMed

Yoon, HeungSik; Kim, Shin Ah; Kim, Sang Hee

2015-06-17

An individual's responses to emotional information are influenced not only by the emotional quality of the information, but also by the context in which the information is presented. We hypothesized that facial expressions of happiness and anger would serve as primes to modulate subjective and neural responses to subsequently presented negative information. To test this hypothesis, we conducted a functional MRI study in which the brains of healthy adults were scanned while they performed an emotion-rating task. During the task, participants viewed a series of negative and neutral photos, one at a time; each photo was presented after a picture showing a face expressing a happy, angry, or neutral emotion. Brain imaging results showed that compared with neutral primes, happy facial primes increased activation during negative emotion in the dorsal anterior cingulated cortex and the right ventrolateral prefrontal cortex, which are typically implicated in conflict detection and implicit emotion control, respectively. Conversely, relative to neutral primes, angry primes activated the right middle temporal gyrus and the left supramarginal gyrus during the experience of negative emotion. Activity in the amygdala in response to negative emotion was marginally reduced after exposure to happy primes compared with angry primes. Relative to neutral primes, angry facial primes increased the subjectively experienced intensity of negative emotion. The current study results suggest that prior exposure to facial expressions of emotions modulates the subsequent experience of negative emotion by implicitly activating the emotion-regulation system.

Noradrenergic Mechanisms of Arousal’s Bidirectional Effects on Episodic Memory

PubMed Central

Clewett, David; Sakaki, Michiko; Nielsen, Shawn; Petzinger, Giselle; Mather, Mara

2016-01-01

Arousal’s selective effects on cognition go beyond the simple enhancement of emotional stimuli, sometimes enhancing and other times impairing processing of proximal neutral information. Past work shows that arousal impairs encoding of subsequent neutral stimuli regardless of their top-down priority via the engagement of β-adrenoreceptors. In contrast, retrograde amnesia induced by emotional arousal can flip to enhancement when preceding neutral items are prioritized in top-down attention. Whether β-adrenoreceptors also contribute to this retrograde memory enhancement of goal-relevant neutral stimuli is unclear. In this pharmacological study, we administered 40mg of propranolol or 40mg of placebo to healthy young adults to examine whether emotional arousal’s bidirectional effects on declarative memory relies on β-adrenoreceptor activation. Following pill intake, participants completed an emotional oddball task in which they were asked to prioritize a neutral object appearing just before an emotional or neutral oddball image within a sequence of 7 neutral objects. Under placebo, emotional oddballs impaired memory for lower priority oddball+1 objects but had no effect on memory for high priority oddball−1 objects. Propranolol blocked this anterograde amnesic effect of arousal. Emotional oddballs also enhanced selective memory trade-offs significantly more in the placebo than drug condition, such that high priority oddball−1 objects were more likely to be remembered at the cost of their corresponding lower priority oddball+1 objects under arousal. Lastly, those who recalled more high priority oddball−1 objects preceding an emotional versus neutral oddball image showed greater increases in salivary alpha-amylase, a biomarker of noradrenergic system activation, across the task. Together these findings suggest that different noradrenergic mechanisms contribute to the anterograde and retrograde mnemonic effects of arousal on proximal neutral memoranda. PMID:27815214

Fine epitope signature of antibody neutralization breadth at the HIV-1 envelope CD4-binding site.

PubMed

Cheng, Hao D; Grimm, Sebastian K; Gilman, Morgan Sa; Gwom, Luc Christian; Sok, Devin; Sundling, Christopher; Donofrio, Gina; Hedestam, Gunilla B Karlsson; Bonsignori, Mattia; Haynes, Barton F; Lahey, Timothy P; Maro, Isaac; von Reyn, C Fordham; Gorny, Miroslaw K; Zolla-Pazner, Susan; Walker, Bruce D; Alter, Galit; Burton, Dennis R; Robb, Merlin L; Krebs, Shelly J; Seaman, Michael S; Bailey-Kellogg, Chris; Ackerman, Margaret E

2018-03-08

Major advances in donor identification, antigen probe design, and experimental methods to clone pathogen-specific antibodies have led to an exponential growth in the number of newly characterized broadly neutralizing antibodies (bnAbs) that recognize the HIV-1 envelope glycoprotein. Characterization of these bnAbs has defined new epitopes and novel modes of recognition that can result in potent neutralization of HIV-1. However, the translation of envelope recognition profiles in biophysical assays into an understanding of in vivo activity has lagged behind, and identification of subjects and mAbs with potent antiviral activity has remained reliant on empirical evaluation of neutralization potency and breadth. To begin to address this discrepancy between recombinant protein recognition and virus neutralization, we studied the fine epitope specificity of a panel of CD4-binding site (CD4bs) antibodies to define the molecular recognition features of functionally potent humoral responses targeting the HIV-1 envelope site bound by CD4. Whereas previous studies have used neutralization data and machine-learning methods to provide epitope maps, here, this approach was reversed, demonstrating that simple binding assays of fine epitope specificity can prospectively identify broadly neutralizing CD4bs-specific mAbs. Building on this result, we show that epitope mapping and prediction of neutralization breadth can also be accomplished in the assessment of polyclonal serum responses. Thus, this study identifies a set of CD4bs bnAb signature amino acid residues and demonstrates that sensitivity to mutations at signature positions is sufficient to predict neutralization breadth of polyclonal sera with a high degree of accuracy across cohorts and across clades.

Noradrenergic mechanisms of arousal's bidirectional effects on episodic memory.

PubMed

Clewett, David; Sakaki, Michiko; Nielsen, Shawn; Petzinger, Giselle; Mather, Mara

2017-01-01

Arousal's selective effects on cognition go beyond the simple enhancement of emotional stimuli, sometimes enhancing and other times impairing processing of proximal neutral information. Past work shows that arousal impairs encoding of subsequent neutral stimuli regardless of their top-down priority via the engagement of β-adrenoreceptors. In contrast, retrograde amnesia induced by emotional arousal can flip to enhancement when preceding neutral items are prioritized in top-down attention. Whether β-adrenoreceptors also contribute to this retrograde memory enhancement of goal-relevant neutral stimuli is unclear. In this pharmacological study, we administered 40mg of propranolol or 40mg of placebo to healthy young adults to examine whether emotional arousal's bidirectional effects on declarative memory relies on β-adrenoreceptor activation. Following pill intake, participants completed an emotional oddball task in which they were asked to prioritize a neutral object appearing just before an emotional or neutral oddball image within a sequence of 7 neutral objects. Under placebo, emotional oddballs impaired memory for lower priority oddball+1 objects but had no effect on memory for high priority oddball-1 objects. Propranolol blocked this anterograde amnesic effect of arousal. Emotional oddballs also enhanced selective memory trade-offs significantly more in the placebo than drug condition, such that high priority oddball-1 objects were more likely to be remembered at the cost of their corresponding lower priority oddball+1 objects under arousal. Lastly, those who recalled more high priority oddball-1 objects preceding an emotional versus neutral oddball image showed greater increases in salivary alpha-amylase, a biomarker of noradrenergic system activation, across the task. Together these findings suggest that different noradrenergic mechanisms contribute to the anterograde and retrograde mnemonic effects of arousal on proximal neutral memoranda. Copyright © 2016 Elsevier Inc. All rights reserved.

Gas pressure and electron density at the level of the active zone of hollow cathode arc discharges

NASA Technical Reports Server (NTRS)

Minoo, M. H.

1984-01-01

A model for the longitudinal variations of the partial pressures of electrons, ions, and neutral particles is proposed as a result of an experimental study of pressure variations at the level of the active zone as a function of the various discharge parameters of a hollow cathode arc. The cathode region where the temperature passes through its maximum is called active zone. The proposed model embodies the very important variations which the partial electron and neutral particles pressures undergo at the level of the active zone.

Patient-Specific Neutralizing Antibody Responses to Herpes Simplex Virus Are Attributed to Epitopes on gD, gB, or Both and Can Be Type Specific

PubMed Central

Huang, Zhen-Yu; Gallagher, John R.; Lin, Yixin; Lou, Huan; Whitbeck, J. Charles; Wald, Anna; Cohen, Gary H.; Eisenberg, Roselyn J.

2015-01-01

ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 infect many humans and establish a latent infection in sensory ganglia. Although some infected people suffer periodic recurrences, others do not. Infected people mount both cell-mediated and humoral responses, including the production of virus-neutralizing antibodies (Abs) directed at viral entry glycoproteins. Previously, we examined IgGs from 10 HSV-seropositive individuals; all neutralized virus and were directed primarily against gD or gD+gB. Here, we expand our studies and examine 32 additional sera from HSV-infected individuals, 23 of whom had no recurrent disease. Using an Octet RED96 system, we screened all 32 serum samples directly for both glycoprotein binding and competition with known neutralizing anti-gD and -gB monoclonal Abs (MAbs). On average, the recurrent cohort exhibited higher binding to gD and gB and had higher neutralization titers. There were similar trends in the blocking of MAbs to critical gD and gB epitopes. When we depleted six sera of Abs to specific glycoproteins, we found different types of responses, but always directed primarily at gD and/or gB. Interestingly, in one dual-infected person, the neutralizing response to HSV-2 was due to gD2 and gB2, whereas HSV-1 neutralization was due to gD1 and gB1. In another case, virus neutralization was HSV-1 specific, with the Ab response directed entirely at gB1, despite this serum blocking type-common anti-gD and -gB neutralizing MAbs. These data are pertinent in the design of future HSV vaccines since they demonstrate the importance of both serotypes of gD and gB as immunogens. IMPORTANCE We previously showed that people infected with HSV produce neutralizing Abs directed against gD or a combination of gD+gB (and in one case, gD+gB+gC, which was HSV-1 specific). In this more extensive study, we again found that gD or gD+gB can account for the virus neutralizing response and critical epitopes of one or both of these proteins are represented in sera of naturally infected humans. However, we also found that some individuals produced a strong response against gB alone. In addition, we identified type-specific contributions to HSV neutralization from both gD and gB. Contributions from the other entry glycoproteins, gC and gH/gL, were minimal and limited to HSV-1 neutralization. Knowing the variations in how humans see and mount a response to HSV will be important to vaccine development. PMID:26109729

Synthetic bioactive novel ether based Schiff bases and their copper(II) complexes

NASA Astrophysics Data System (ADS)

Shabbir, Muhammad; Akhter, Zareen; Ismail, Hammad; Mirza, Bushra

2017-10-01

Novel ether based Schiff bases (HL1- HL4) were synthesized from 5-chloro-2-hydroxy benzaldehyde and primary amines (1-amino-4-phenoxybenzene, 4-(4-aminophenyloxy) biphenyl, 1-(4-aminophenoxy) naphthalene and 2-(4-aminophenoxy) naphthalene). From these Schiff bases copper(II) complexes (Cu(L1)2-Cu(L4)2)) were synthesized and characterized by elemental analysis and spectroscopic (FTIR, NMR) techniques. The synthesized Schiff bases and copper(II) complexes were further assessed for various biological studies. In brine shrimp assay the copper(II) complexes revealed 4-fold higher activity (LD50 3.8 μg/ml) as compared with simple ligands (LD50 12.4 μg/ml). Similar findings were observed in potato disc antitumor assay with higher activities for copper(II) complexes (IC50 range 20.4-24.1 μg/ml) than ligands (IC50 range 40.5-48.3 μg/ml). DPPH assay was performed to determine the antioxidant potential of the compounds. Significant antioxidant activity was shown by the copper(II) complexes whereas simple ligands have shown no activity. In DNA protection assay significant protection behavior was exhibited by simple ligand molecules while copper(II) complexes showed neutral behavior (neither protective nor damaging).

Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging.

PubMed

Due, Deborah L; Huettel, Scott A; Hall, Warren G; Rubin, David C

2002-06-01

The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers. Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smoking-related images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions.

Antioxidative defence mechanisms against reactive oxygen species in bovine retained and not-retained placenta: activity of glutathione peroxidase, glutathione transferase, catalase and superoxide dismutase.

PubMed

Kankofer, M

2001-05-01

Glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), catalase (CAT) and superoxide dismutase (SOD)-the members of enzymatic antioxidative defence mechanisms against reactive oxygen species-may play an important role in proper or improper release of bovine fetal membranes. The aim of the following study was the determination of GSH-Px, GSH-Tr, CAT and SOD activity in order to define antioxidative status of bovine placenta during retention of fetal membranes (RFM) in cows. Placental samples were collected immediately after spontaneous parturition or during caesarean section before term and at term and divided into six groups as follows: A: caesarean section before term without RFM; B: caesarean section before term with RFM; C: caesarean section at term without RFM; D: caesarean section at term with RFM; E: spontaneous delivery at term without RFM; F: spontaneous delivery at term with RFM. The enzyme activities in placental homogenates were measured spectrophotometrically. GSH-Px activity was statistically significantly higher in fetal than in maternal placenta in all examined groups, increased towards parturition and was higher in caesarean section groups than spontaneous delivery groups. Statistically significantly higher activities were noticed in retained than not-retained placentae. GSH-Tr activity was significantly lower in fetal than in maternal placenta. In preterm groups, the activity was statistically significantly higher in retained than not retained placenta. In term groups, the opposite relationship was observed, higher values in caesarean section groups than spontaneous delivery were noticed. CAT activity was statistically significantly higher in fetal than in maternal part of placenta in all groups examined. The highest values in C and D groups and the differences between retained and not-retained placenta were observed. SOD exhibited the highest values in preterm placenta and alterations between retained and not-retained fetal membranes. In conclusion, the activities of GSH-Px, GSH-Tr, CAT and SOD are altered in cases of retained fetal membranes which may suggest the activation of antioxidative mechanisms caused by the imbalance between production and neutralization of reactive oxygen species. Copyright 2001 Harcourt Publishers Ltd.

Novel biomaterials: plasma-enabled nanostructures and functions

NASA Astrophysics Data System (ADS)

Levchenko, Igor; Keidar, Michael; Cvelbar, Uroš; Mariotti, Davide; Mai-Prochnow, Anne; Fang, Jinghua; (Ken Ostrikov, Kostya

2016-07-01

Material processing techniques utilizing low-temperature plasmas as the main process tool feature many unique capabilities for the fabrication of various nanostructured materials. As compared with the neutral-gas based techniques and methods, the plasma-based approaches offer higher levels of energy and flux controllability, often leading to higher quality of the fabricated nanomaterials and sometimes to the synthesis of the hierarchical materials with interesting properties. Among others, nanoscale biomaterials attract significant attention due to their special properties towards the biological materials (proteins, enzymes), living cells and tissues. This review briefly examines various approaches based on the use of low-temperature plasma environments to fabricate nanoscale biomaterials exhibiting high biological activity, biological inertness for drug delivery system, and other features of the biomaterials make them highly attractive. In particular, we briefly discuss the plasma-assisted fabrication of gold and silicon nanoparticles for bio-applications; carbon nanoparticles for bioimaging and cancer therapy; carbon nanotube-based platforms for enzyme production and bacteria growth control, and other applications of low-temperature plasmas in the production of biologically-active materials.

A comparison of neutral and immune genetic variation in Atlantic salmon, Salmo salar L. in Chilean aquaculture facilities.

PubMed

Portnoy, David S; Hollenbeck, Christopher M; Vidal, R Rodrigo; Gold, John R

2014-01-01

Genetic diversity was assessed in samples of cultured Atlantic salmon, Salmo salar L., obtained from facilities in Chile between 2005 and 2010, a period of time during which the infectious pathogens Infectious Salmon Anemia (ISA) virus, Caligus rogercresseyi (sea lice), and Piscirickettsia salmonis (salmon rickettsial syndrome) were common. Two panels of microsatellite markers were utilized: one with microsatellites with no known gene associations (neutral) and one featuring microsatellites linked to putative immune-related genes (immune-related). Allelic richness and gene diversity across samples were significantly greater in neutral loci as compared to immune-related loci. Both diversity measures were homogeneous among samples for immune-related loci and heterogeneous among samples for neutral loci. Immune-related loci were identified as F(ST) outliers in pairwise comparisons of samples at a 10-fold higher frequency than neutral loci. These results indicate that neutral and immune-related portions of the Atlantic salmon genome may have differed in response to the gauntlet of pathogens and that monitoring of specific, well characterized immune-related loci as well as neutral loci in cultured species could be useful when disease control and prevention is a goal.

Morphological characteristics in peritoneum in patients with neutral peritoneal dialysis solution.

PubMed

Hamada, Chieko; Honda, Kazuho; Kawanishi, Kunio; Nakamoto, Hirotaka; Ito, Yasuhiko; Sakurada, Tsutomu; Tanno, Yudo; Mizumasa, Toru; Miyazaki, Masanobu; Moriishi, Misaki; Nakayama, Masaaki

2015-09-01

Peritoneal dialysis solution (PDS) plays a role in functional and morphological damage to the peritoneum. This study aimed to clarify the effect of neutral PDS in preventing morphological changes by assessing peritoneal damage and comparing morphological alterations between PD patients treated with neutral PDS and acidic PDS. Sixty-one patients participated from seven hospitals. All patients were treated with neutral PDS excluding icodextrin, during their entire PD treatment, and experienced no episode of peritonitis. The thickness of submesothelial compact (SMC) zone and the presence of vasculopathy in the anterior parietal abdominal peritoneum were assessed. The impact of icodextrin, hybrid therapy, and peritoneal rest and lavage in morphological alterations were determined. There was no significant difference in the average SMC thickness between neutral and acidic PDS. The vessel patency in patients using neutral PDS was significantly higher compared to that in acidic PDS at any time during PD. There were no significant suppressive effects from interventions or use of icodextrin with respect to peritoneal morphological injury. A monolayer of mesothelial cell was observed in approximately half the patients, especially in their receiving lavage patients. Neutral PDS, accompanied by other preventive approaches against peritoneal injury, might suppress the development of peritoneal morphological alterations.

A Comparison of Neutral and Immune Genetic Variation in Atlantic Salmon, Salmo salar L. in Chilean Aquaculture Facilities

PubMed Central

Portnoy, David S.; Hollenbeck, Christopher M.; Vidal, R. Rodrigo; Gold, John R.

2014-01-01

Genetic diversity was assessed in samples of cultured Atlantic salmon, Salmo salar L., obtained from facilities in Chile between 2005 and 2010, a period of time during which the infectious pathogens Infectious Salmon Anemia (ISA) virus, Caligus rogercresseyi (sea lice), and Piscirickettsia salmonis (salmon rickettsial syndrome) were common. Two panels of microsatellite markers were utilized: one with microsatellites with no known gene associations (neutral) and one featuring microsatellites linked to putative immune-related genes (immune-related). Allelic richness and gene diversity across samples were significantly greater in neutral loci as compared to immune-related loci. Both diversity measures were homogeneous among samples for immune-related loci and heterogeneous among samples for neutral loci. Immune-related loci were identified as FST outliers in pairwise comparisons of samples at a 10-fold higher frequency than neutral loci. These results indicate that neutral and immune-related portions of the Atlantic salmon genome may have differed in response to the gauntlet of pathogens and that monitoring of specific, well characterized immune-related loci as well as neutral loci in cultured species could be useful when disease control and prevention is a goal. PMID:24918941

Do Astronauts have a Higher Rate of Orthopedic Shoulder Conditions than a Cohort of Working Professionals?

NASA Technical Reports Server (NTRS)

Laughlin, Mitzi S.; Murray, Jocelyn D.; Young, Millenia; Wear, Mary L.; Tarver, W. J.; Van Baalen, Mary

2016-01-01

Occupational surveillance of astronaut shoulder injuries began with operational concerns at the Neutral Buoyancy Laboratory (NBL) during Extra Vehicular Activity (EVA) training. NASA has implemented several occupational health initiatives during the past 20 years to decrease the number and severity of injuries, but the individual success rate is unknown. Orthopedic shoulder injury and surgery rates were calculated, but classifying the rates as normal, high or low was highly dependent on the comparison group. The purpose of this study was to identify a population of working professionals and compare orthopedic shoulder consultation and surgery rates.

Target Gas Effects on Collision-Induced Dissociation of Peptides in a Tandem Four-Sector Mass Spectrometer.

DTIC Science & Technology

1991-05-01

it is due to lysine and/or pyroglutamic acid . No data were given to support this so experiments were conducted to attempt to confirm the source and the...fragmentation pathways with higher activation energies than by simple cleavages between amino acid residues or by losses of simple neutrals such as...Avg Mass Compound Avg Mass H2 1.01 Acetic Acid 5.50 H20 6.00 Alanine 6.85 C02 - 14.66 Glucose 7.51 CH4 3.2i Benzene 6.51 MeOH 5.34 Butanol 4.94

Plasma waves at comet 67P/Churyumov-Gerasimenko: in the diamagnetic cavity and outside it

NASA Astrophysics Data System (ADS)

Gunell, Herbert; Altwegg, Kathrin; Cessateur, Gaël; De Keyser, Johan; Dhooghe, Frederik; Eriksson, Anders; Gibbons, Andrew; Glassmeier, Karl-Heinz; Goetz, Charlotte; Karlsson, Tomas; Hamrin, Maria; Henri, Pierre; Maggiolo, Romain; Nilsson, Hans; Odelstad, Elias; Rubin, Martin; Wedlund, Cyril Simon; Stenberg Wieser, Gabriella; Tzou, Chia-Yu; Vallieres, Xavier

2017-04-01

We present observations of waves at Comet 67P/Churyumov-Gerasimenko performed on 20 January 2015, when the activity of the comet was low, and in July and August 2015 when the activity had increased and the Rosetta spacecraft passed through the diamagnetic cavity several times. We use distribution functions obtained by the Ion Composition Analyser of the Rosetta Plasma Consortium (RPC-ICA) and electron temperature estimates from the Langmuir Probes (RPC-LAP) to compute dispersion relations for waves on the ion timescale, and we compare the results to spectra obtained by RPC-LAP. On 20 January 2015, at low activity, peaks of the wave spectra appeared at frequencies near 500 Hz, and we identify these waves as ion acoustic. We performed cross-calibrations between RPC-ICA, RPC-LAP, and the Mutual Impedance Probe (RPC-MIP) in order to determine the plasma density. Matching the dispersion relations to the wave observations also helps us estimating the density. We explore the relationship between the waves, the ion distribution functions, and the neutral density, which was measured by the ROSINA-COPS instrument. It is found that when the waves are seen, the ion temperature is low (approximately 0.01 eV). At times the ion temperature is higher (approximately 1 eV), approaching the electron temperature, which leads to strong damping of the ion acoustic waves. This happens when the neutral density is high, suggesting that the ions are heated by being accelerated by the solar wind electric field and scattered in collisions with the neutrals. These results are compared to measurements of wave spectra when Rosetta was inside the diamagnetic cavity in July and August 2015. In the cavity, the plasma is effectively unmagnetised. We identify cavity passages using the magnetometer RPC-MAG. The waves are analysed in the same way as in the earlier measurements outside the cavity, and the two cases are compared.

Analysis of Alfven eigenmode destabilization in DIII-D high poloidal β discharges using a Landau closure model

NASA Astrophysics Data System (ADS)

Varela, J.; Spong, D. A.; Garcia, L.; Huang, J.; Murakami, M.; Garofalo, A. M.; Qian, J. P.; Holcomb, C. T.; Hyatt, A. W.; Ferron, J. R.; Collins, C. S.; Ren, Q. L.; McClenaghan, J.; Guo, W.

2018-07-01

Alfvén eigenmodes are destabilized at the DIII-D pedestal during transient beta drops in high poloidal β discharges with internal transport barriers (ITBs), driven by n  =  1 external kink modes, leading to energetic particle losses. There are two different scenarios in the thermal β recovery phase: with bifurcation (two instability branches with different frequencies) or without bifurcation (single instability branch). We use the reduced MHD equations in a full 3D system, coupled with equations of density and parallel velocity moments for the energetic particles as well as the geodesic acoustic wave dynamics, to study the properties of the instabilities observed in the DIII-D high poloidal β discharges and identify the conditions to trigger the bifurcation. The simulations suggest that instabilities with lower frequency in the bifurcation case are ballooning modes driven at the plasma pedestal, while the instability branch with higher frequencies are low n (n  <  4) toroidal Alfvén eigenmodes nearby the pedestal. The reverse shear region between the middle and plasma periphery in the non-bifurcated case avoids the excitation of ballooning modes at the pedestal, although toroidal Alfvén eigenmodes and reverse shear Alfvén eigenmodes are unstable in the reverse shear region. The n  =  1 and n  =  2 Alfvén eigenmode activity can be suppressed or minimized if the neutral beam injector (NBI) intensity is lower than the experimental value (). In addition, if the beam energy or neutral beam injector voltage is lower than in the experiment (), the resonance between beam and thermal plasma is weaker. The and 6 AE activity can not be fully suppressed, although the growth rate and frequency is smaller for an optimized neutral beam injector operation regime. In conclusion, AE activity in high poloidal β discharges can be minimized for optimized NBI operation regimes.

Study of the combined effect of electro-activated solutions and heat treatment on the destruction of spores of Clostridium sporogenes and Geobacillus stearothermophilus in model solution and vegetable puree.

PubMed

Liato, Viacheslav; Labrie, Steve; Viel, Catherine; Benali, Marzouk; Aïder, Mohammed

2015-10-01

The combined effect of heat treatment and electro-activated solution (EAS) on the heat resistance of spores of Clostridium sporogenes and Geobacillus stearothermophilus was assessed under various heating and exposure time combinations. The acid and neutral EAS showed the highest inhibitory activity, indicating that these solutions may be considered as strong sporicidal disinfectants. These EAS were able to cause a reduction of ≥6 log of spores of C. sporogenes at 60 °C in only 1 min of exposition. For G. stearothermophilus spores, a reduction of 4.5 log was observed at 60 °C in 1 min, while in 5 min, ≥7 log CFU/ml reduction was observed. Inoculated puree of pea and corn were used as a food matrix for the determination of the heat resistance of these spores during the treatments in glass capillaries. The inactivation kinetics of the spores was studied in an oil bath. Combined treatment by EAS and temperature demonstrated a significant decrease in the heat resistance of C. sporogenes. The D100°C in pea puree with NaCl solution was 66.86 min while with acid and neutral EAS it was reduced down to 3.97 and 2.19 min, respectively. The spore of G. stearothermophilus displayed higher heat resistance as confirmed by other similar studies. Its D130°C in pea puree showed a decrease from 1.45 min in NaCl solution down to 1.30 and 0.93 min for acid and neutral EAS, respectively. The differences between the spores of these species are attributable to their different sensitivities with respect to pH, Redox potential and oxygen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perceived moral traits of others differentiate the neural activation that underlies inequity-aversion

PubMed Central

Nakatani, Hironori; Ogawa, Akitoshi; Suzuki, Chisato; Asamizuya, Takeshi; Ueno, Kenichi; Cheng, Kang; Okanoya, Kazuo

2017-01-01

We have a social preference to reduce inequity in the outcomes between oneself and others. Such a preference varies according to others. We performed functional magnetic resonance imaging during an economic game to investigate how the perceived moral traits of others modulate the neural activities that underlie inequity-aversion. The participants unilaterally allocated money to three partners (good, neutral, and bad). During presentation of the good and neutral partners, the anterior region of the rostral medial frontal cortex (arMFC) showed increased functional connectivity with the caudate head and the anterior insula, respectively. Following this, participants allocated more money to the good partner, and less to the bad partner, compared with the neutral partner. The caudate head and anterior insula showed greater activation during fair allocation to the good and unfair allocation to the neutral partners, respectively. However, these regions were silent during allocations to the bad partner. Therefore, the arMFC-caudate/insula circuit encompasses distinct neural processes that underlie inequity-aversion in monetary allocations that the different moral traits of others can modulate. PMID:28230155

Difficulty identifying feelings and automatic activation in the fusiform gyrus in response to facial emotion.

PubMed

Eichmann, Mischa; Kugel, Harald; Suslow, Thomas

2008-12-01

Difficulties in identifying and differentiating one's emotions are a central characteristic of alexithymia. In the present study, automatic activation of the fusiform gyrus to facial emotion was investigated as a function of alexithymia as assessed by the 20-item Toronto Alexithymia Scale. During 3 Tesla fMRI scanning, pictures of faces bearing sad, happy, and neutral expressions masked by neutral faces were presented to 22 healthy adults who also responded to the Toronto Alexithymia Scale. The fusiform gyrus was selected as the region of interest, and voxel values of this region were extracted, summarized as means, and tested among the different conditions (sad, happy, and neutral faces). Masked sad facial emotions were associated with greater bilateral activation of the fusiform gyrus than masked neutral faces. The subscale, Difficulty Identifying Feelings, was negatively correlated with the neural response of the fusiform gyrus to masked sad faces. The correlation results suggest that automatic hyporesponsiveness of the fusiform gyrus to negative emotion stimuli may reflect problems in recognizing one's emotions in everyday life.

Prediction of Protection against Asian Enterovirus 71 Outbreak Strains by Cross-neutralizing Capacity of Serum from Dutch Donors, The Netherlands

PubMed Central

Koen, Gerrit; van Eijk, Hetty; Koekkoek, Sylvie M.; de Jong, Menno D.; Wolthers, Katja C.

2016-01-01

Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from donors in the Netherlands against EV-71 strains isolated in Europe and in Asia. All IVIg batches and 41%, 79%, and 65% of serum samples from children ≤5 years of age, women of childbearing age, and HIV-positive men, respectively, showed high neutralizing activity against a Dutch C1 strain, confirming widespread circulation of EV-71 in the Netherlands. Asian B3–4 and C4 strains were efficiently cross-neutralized, predicting possible protection against extensive circulation and associated outbreaks of those types in Europe. However, C2 and C5 strains that had few mutations in the capsid region consistently escaped neutralization, emphasizing the importance of monitoring antigenic diversity among circulating EV-71 strains. PMID:27533024

Saturn Ring

NASA Image and Video Library

2007-12-12

Like Earth, Saturn has an invisible ring of energetic ions trapped in its magnetic field. This feature is known as a "ring current." This ring current has been imaged with a special camera on Cassini sensitive to energetic neutral atoms. This is a false color map of the intensity of the energetic neutral atoms emitted from the ring current through a processed called charged exchange. In this process a trapped energetic ion steals and electron from cold gas atoms and becomes neutral and escapes the magnetic field. The Cassini Magnetospheric Imaging Instrument's ion and neutral camera records the intensity of the escaping particles, which provides a map of the ring current. In this image, the colors represent the intensity of the neutral emission, which is a reflection of the trapped ions. This "ring" is much farther from Saturn (roughly five times farther) than Saturn's famous icy rings. Red in the image represents the higher intensity of the particles, while blue is less intense. Saturn's ring current had not been mapped before on a global scale, only "snippets" or areas were mapped previously but not in this detail. This instrument allows scientists to produce movies (see PIA10083) that show how this ring changes over time. These movies reveal a dynamic system, which is usually not as uniform as depicted in this image. The ring current is doughnut shaped but in some instances it appears as if someone took a bite out of it. This image was obtained on March 19, 2007, at a latitude of about 54.5 degrees and radial distance 1.5 million kilometres (920,000 miles). Saturn is at the center, and the dotted circles represent the orbits of the moon's Rhea and Titan. The Z axis points parallel to Saturn's spin axis, the X axis points roughly sunward in the sun-spin axis plane, and the Y axis completes the system, pointing roughly toward dusk. The ion and neutral camera's field of view is marked by the white line and accounts for the cut-off of the image on the left. The image is an average of the activity over a (roughly) 3-hour period. http://photojournal.jpl.nasa.gov/catalog/PIA10094

The impacts of neutralized acid mine drainage contaminated water on the expression of selected endocrine-linked genes in juvenile Mozambique tilapia Oreochromis mossambicus exposed in vivo.

PubMed

Truter, Johannes Christoff; va Wyk, Johannes Hendrik; Oberholster, Paul Johan; Botha, Anna-Maria

2014-02-01

Acid mine drainage (AMD) is a global environmental concern due to detrimental impacts on river ecosystems. Little is however known regarding the biological impacts of neutralized AMD on aquatic vertebrates despite excessive discharge into watercourses. The aim of this investigation was to evaluate the endocrine modulatory potential of neutralized AMD, using molecular biomarkers in the teleost fish Oreochromis mossambicus in exposure studies. Surface water was collected from six locations downstream of a high density sludge (HDS) AMD treatment plant and a reference site unimpacted by AMD. The concentrations of 28 elements, including 22 metals, were quantified in the exposure water in order to identify potential links to altered gene expression. Relatively high concentrations of manganese (~ 10mg/l), nickel (~ 0.1mg/l) and cobalt (~ 0.03 mg/l) were detected downstream of the HDS plant. The expression of thyroid receptor-α (trα), trβ, androgen receptor-1 (ar1), ar2, glucocorticoid receptor-1 (gr1), gr2, mineralocorticoid receptor (mr) and aromatase (cyp19a1b) was quantified in juvenile fish after 48 h exposure. Slight but significant changes were observed in the expression of gr1 and mr in fish exposed to water collected directly downstream of the HDS plant, consisting of approximately 95 percent neutralized AMD. The most pronounced alterations in gene expression (i.e. trα, trβ, gr1, gr2, ar1 and mr) was associated with water collected further downstream at a location with no other apparent contamination vectors apart from the neutralized AMD. The altered gene expression associated with the "downstream" locality coincided with higher concentrations of certain metals relative to the locality adjacent to the HDS plant which may indicate a causative link. The current study provides evidence of endocrine disruptive activity associated with neutralized AMD contamination in regard to alterations in the expression of key genes linked to the thyroid, interrenal and gonadal endocrine axes of a teleost fish species. © 2013 Published by Elsevier Inc.

Glycosylation analysis of recombinant neutral protease I from Aspergillus oryzae expressed in Pichia pastoris.

PubMed

Lei, Da; Xu, Yang; He, Qinghua; Pang, Yifeng; Chen, Bo; Xiong, Liang; Li, Yanping

2013-12-01

Neutral protease I from Aspergillus oryzae 3.042 was expressed in Pichia pastoris and its N-glycosylation properties were analyzed. After purification by nickel-affinity chromatography column, the recombinant neutral protease (rNPI) was confirmed to be N-glycosylated by periodicacid/Schiff's base staining and Endo H digestion. Moreover, the deglycosylated protein's molecular weight decreased to 43.3 kDa from 54.5 kDa analyzed by SDS-PAGE and MALDI-TOF-MS, and the hyperglycosylation extent was 21 %. The N-glycosylation site of rNPI was analyzed by nano LC-MS/MS after digesting by trypsin and Glu-C, and the unique potential site Asn41 of mature peptide was found to be glycosylated. Homology modeling of the 3D structure of rNPI indicated that the attached N-glycans hardly affected neutral protease's activity due to the great distance away from the active site of the enzyme.

TNF-α and Temporal Changes in Sleep Architecture in Mice Exposed to Sleep Fragmentation

PubMed Central

2012-01-01

TNF-α plays critical roles in host-defense, sleep-wake regulation, and the pathogenesis of various disorders. Increases in the concentration of circulating TNF-α after either sleep deprivation or sleep fragmentation (SF) appear to underlie excessive daytime sleepiness in patients with sleep apnea (OSA). Following baseline recordings, mice were subjected to 15 days of SF (daily for 12 h/day from 07.00 h to 19.00 h), and sleep parameters were recorded on days1, 7 and 15. Sleep architecture and sleep propensity were assessed in both C57BL/6J and in TNF-α double receptor KO mice (TNFR KO). To further confirm the role of TNF-α, we also assessed the effect of treatment with a TNF- α neutralizing antibody in C57BL/6J mice. SF was not associated with major changes in global sleep architecture in C57BL/6J and TNFR KO mice. TNFR KO mice showed higher baseline SWS delta power. Further, following 15 days of SF, mice injected with TNF-α neutralizing antibody and TNFR KO mice showed increased EEG SWS activity. However, SWS latency, indicative of increased propensity to sleep, was only decreased in C57BL/6J, and was unaffected in TNFR KO mice as well as in C57BL/6J mice exposed to SF but treated with TNF-α neutralizing antibody. Taken together, our findings show that the excessive sleepiness incurred by recurrent arousals during sleep may be due to activation of TNF-alpha-dependent inflammatory pathways, despite the presence of preserved sleep duration and global sleep architecture. PMID:23029133

Utilization of Electrically Reduced Neutral Red by Actinobacillus succinogenes: Physiological Function of Neutral Red in Membrane-Driven Fumarate Reduction and Energy Conservation

PubMed Central

Park, D. H.; Zeikus, J. G.

1999-01-01

Neutral red (NR) functioned as an electronophore or electron channel enabling either cells or membranes purified from Actinobacillus succinogenes to drive electron transfer and proton translocation by coupling fumarate reduction to succinate production. Electrically reduced NR, unlike methyl or benzyl viologen, bound to cell membranes, was not toxic, and chemically reduced NAD. The cell membrane of A. succinogenes contained high levels of benzyl viologen-linked hydrogenase (12.2 U), fumarate reductase (13.1 U), and diaphorase (109.7 U) activities. Fumarate reductase (24.5 U) displayed the highest activity with NR as the electron carrier, whereas hydrogenase (1.1 U) and diaphorase (0.8 U) did not. Proton translocation by whole cells was dependent on either electrically reduced NR or H2 as the electron donor and on the fumarate concentration. During the growth of Actinobacillus on glucose plus electrically reduced NR in an electrochemical bioreactor system versus on glucose alone, electrically reduced NR enhanced glucose consumption, growth, and succinate production by about 20% while it decreased acetate production by about 50%. The rate of fumarate reduction to succinate by purified membranes was twofold higher with electrically reduced NR than with hydrogen as the electron donor. The addition of 2-(n-heptyl)-4-hydroxyquinoline N-oxide to whole cells or purified membranes inhibited succinate production from H2 plus fumarate but not from electrically reduced NR plus fumarate. Thus, NR appears to replace the function of menaquinone in the fumarate reductase complex, and it enables A. succinogenes to utilize electricity as a significant source of metabolic reducing power. PMID:10198002

Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system.

PubMed

Jia, Xuanyan; Yao, Jianyun; Gao, Zengqiang; Liu, Guangfeng; Dong, Yu-Hui; Wang, Xiaoxue; Zhang, Heng

2018-05-04

Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain have been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis Here, we report the crystal structure and solution conformation of the SO_3166-SO_3165 pair, representing the first complex structures in this TA family. The structures revealed that SO_3165 and SO_3166 form a tight heterooctamer (at a 2:6 ratio), an organization that is very rare in other TA systems. We also observed that SO_3166 dimerization enables the formation of a deep cleft at the HEPN-domain interface harboring a composite R X 4-6H active site that functions as an RNA-cleaving RNase. SO_3165 bound SO_3166 mainly through its two α-helices (α2 and α4), functioning as molecular recognition elements. Moreover, their insertion into the SO_3166 cleft sterically blocked the R X 4-6H site or narrowed the cleft to inhibit RNA substrate binding. Structure-based mutagenesis confirmed the important roles of these α-helices in SO_3166 binding and inhibition. Our structure-function analysis provides first insights into the neutralization mechanism of the HEPN-MNT TA family. © 2018 Jia et al.

Cue reactivity in converted and native intermittent smokers.

PubMed

Shiffman, Saul; Dunbar, Michael S; Kirchner, Thomas R; Li, Xiaoxue; Tindle, Hilary A; Anderson, Stewart J; Scholl, Sarah M; Ferguson, Stuart G

2015-01-01

Nondaily, or intermittent smokers (ITS), who constitute a substantial fraction of U.S. smokers, are thought to smoke in response to cues. Previous cue reactivity research showed no difference between ITS and daily smokers in response to cues. This report examines whether "converted" ITS (CITS) with a history of past daily smoking differ from "native" ITS (NITS) in craving and smoking in response to cues. A total of 146 CITS (who previously smoked daily for at least 6 months) and 73 NITS participated. Participants were exposed to 5 active cues (smoking, alcohol, negative affect, positive affect, and smoking prohibitions) and a control neutral cue, in separate sessions. Changes in craving were assessed pre-post cue exposure. Smoking behavior (smoking [y/n], smoking latency, number of cigarettes, number of puffs, and increase in carbon monoxide [CO]) was observed. Analyses contrasted response to each active cue compared to the neutral cue and controlled for order effects and for time since last cigarette, which differed between groups. Regardless of cues, CITS reported higher craving and greater change in craving, were more likely to smoke, tended to progress faster to smoking, and showed greater increases in CO when they did smoke. NITS and CITS showed similar cue reactivity on most measures, though NITS took more puffs after viewing smoking cues (compared to neutral) than did CITS. Though CITS show some remnants of their history of daily smoking, CITS and NITS demonstrate similar cue reactivity, suggesting that they would not require different behavioral approaches to help them quit. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Using Optimization to Improve NASA Extravehicular Activity Planning

DTIC Science & Technology

2012-09-01

Mission Operations Directorate NASA National Aeronautics and Space Administration NBL Neutral Buoyancy Laboratory ORU Orbital Replacement Unit PET...training is conducted in the Neutral Buoyancy Lab ( NBL ) for full dress rehearsal. The active response gravity offload system is a facility that helps...three NBL runs are dedicated to task and timeline duration validation in normal circumstances, with the possibility of more if the tasks and procedures

Emotional stimuli and motor conversion disorder.

PubMed

Voon, Valerie; Brezing, Christina; Gallea, Cecile; Ameli, Rezvan; Roelofs, Karin; LaFrance, W Curt; Hallett, Mark

2010-05-01

Conversion disorder is characterized by neurological signs and symptoms related to an underlying psychological issue. Amygdala activity to affective stimuli is well characterized in healthy volunteers with greater amygdala activity to both negative and positive stimuli relative to neutral stimuli, and greater activity to negative relative to positive stimuli. We investigated the relationship between conversion disorder and affect by assessing amygdala activity to affective stimuli. We conducted a functional magnetic resonance imaging study using a block design incidental affective task with fearful, happy and neutral face stimuli and compared valence contrasts between 16 patients with conversion disorder and 16 age- and gender-matched healthy volunteers. The patients with conversion disorder had positive movements such as tremor, dystonia or gait abnormalities. We also assessed functional connectivity between the amygdala and regions associated with motor preparation. A group by affect valence interaction was observed. Post hoc analyses revealed that whereas healthy volunteers had greater right amygdala activity to fearful versus neutral compared with happy versus neutral as expected, there were no valence differences in patients with conversion disorder. There were no group differences observed. The time course analysis also revealed greater right amygdala activity in patients with conversion disorder for happy stimuli (t = 2.96, P = 0.006) (with a trend for fearful stimuli, t = 1.81, P = 0.08) compared with healthy volunteers, with a pattern suggestive of impaired amygdala habituation even when controlling for depressive and anxiety symptoms. Using psychophysiological interaction analysis, patients with conversion disorder had greater functional connectivity between the right amygdala and the right supplementary motor area during both fearful versus neutral, and happy versus neutral 'stimuli' compared with healthy volunteers. These results were confirmed with Granger Causality Modelling analysis indicating a directional influence from the right amygdala to the right supplementary motor area to happy stimuli (P < 0.05) with a similar trend observed to fearful stimuli (P = 0.07). Our data provide a potential neural mechanism that may explain why psychological or physiological stressors can trigger or exacerbate conversion disorder symptoms in some patients. Greater functional connectivity of limbic regions influencing motor preparatory regions during states of arousal may underlie the pathophysiology of motor conversion symptoms.

Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent

PubMed Central

Reh, Lucia; Magnus, Carsten; Schanz, Merle; Weber, Jacqueline; Uhr, Therese; Rusert, Peter; Trkola, Alexandra

2015-01-01

An increasing number of broadly neutralizing antibodies (bnAbs) are considered leads for HIV-1 vaccine development and novel therapeutics. Here, we systematically explored the capacity of bnAbs to neutralize HIV-1 prior to and post-CD4 engagement and to block HIV-1 cell-cell transmission. Cell-cell spread is known to promote a highly efficient infection with HIV-1 which can inflict dramatic losses in neutralization potency compared to free virus infection. Selection of bnAbs that are capable of suppressing HIV irrespective of the transmission mode therefore needs to be considered to ascertain their in vivo activity in therapeutic use and vaccines. Employing assay systems that allow for unambiguous discrimination between free virus and cell-cell transmission to T cells, we probed a panel of 16 bnAbs for their activity against 11 viruses from subtypes A, B and C during both transmission modes. Over a wide range of bnAb-virus combinations tested, inhibitory activity against HIV-1 cell-cell transmission was strongly decreased compared to free virus transmission. Activity loss varied considerably between virus strains and was inversely associated with neutralization of free virus spread for V1V2- and V3-directed bnAbs. In rare bnAb-virus combinations, inhibition for both transmission modes was comparable but no bnAb potently blocked cell-cell transmission across all probed virus strains. Mathematical analysis indicated an increased probability of bnAb resistance mutations to arise in cell-cell rather than free virus spread, further highlighting the need to block this pathway. Importantly, the capacity to efficiently neutralize prior to CD4 engagement correlated with the inhibition efficacy against free virus but not cell-cell transmitted virus. Pre-CD4 attachment activity proved strongest amongst CD4bs bnAbs and varied substantially for V3 and V1V2 loop bnAbs in a strain-dependent manner. In summary, bnAb activity against divergent viruses varied depending on the transmission mode and differed depending on the window of action during the entry process, underscoring that powerful combinations of bnAbs are needed for in vivo application. PMID:26158270

Brain oscillations and BIS/BAS (behavioral inhibition/activation system) effects on processing masked emotional cues. ERS/ERD and coherence measures of alpha band.

PubMed

Balconi, Michela; Mazza, Guido

2009-11-01

Alpha brain oscillation modulation was analyzed in response to masked emotional facial expressions. In addition, behavioural activation (BAS) and behavioural inhibition systems (BIS) were considered as an explicative factor to verify the effect of motivational significance on cortical activity. Nineteen subjects were submitted to an ample range of facial expressions of emotions (anger, fear, surprise, disgust, happiness, sadness, and neutral). The results demonstrated that anterior frontal sites were more active than central and posterior sites in response to facial stimuli. Moreover, right-side responses varied as a function of emotional types, with an increased right-frontal activity for negative emotions. Finally, whereas higher BIS subjects generated a more right hemisphere activation for some negative emotions (such as fear, anger, and surprise), Reward-BAS subjects were more responsive to positive emotion (happiness) within the left hemisphere. Valence and potential threatening power of facial expressions were considered to elucidate these cortical differences.

Prediction of pKa Values for Neutral and Basic Drugs based on Hybrid Artificial Intelligence Methods.

PubMed

Li, Mengshan; Zhang, Huaijing; Chen, Bingsheng; Wu, Yan; Guan, Lixin

2018-03-05

The pKa value of drugs is an important parameter in drug design and pharmacology. In this paper, an improved particle swarm optimization (PSO) algorithm was proposed based on the population entropy diversity. In the improved algorithm, when the population entropy was higher than the set maximum threshold, the convergence strategy was adopted; when the population entropy was lower than the set minimum threshold the divergence strategy was adopted; when the population entropy was between the maximum and minimum threshold, the self-adaptive adjustment strategy was maintained. The improved PSO algorithm was applied in the training of radial basis function artificial neural network (RBF ANN) model and the selection of molecular descriptors. A quantitative structure-activity relationship model based on RBF ANN trained by the improved PSO algorithm was proposed to predict the pKa values of 74 kinds of neutral and basic drugs and then validated by another database containing 20 molecules. The validation results showed that the model had a good prediction performance. The absolute average relative error, root mean square error, and squared correlation coefficient were 0.3105, 0.0411, and 0.9685, respectively. The model can be used as a reference for exploring other quantitative structure-activity relationships.

Cannabis and Kratom online information in Thailand: Facebook trends 2015-2016.

PubMed

Thaikla, Kanittha; Pinyopornpanish, Kanokporn; Jiraporncharoen, Wichuda; Angkurawaranon, Chaisiri

2018-05-09

Our study aims to evaluate the trends in online information about cannabis and kratom on Facebook in Thailand, where there is current discussion regarding legalizing these drugs. Between April and November 2015, reviewers searched for cannabis and kratom Facebook pages in the Thai language via the common search engines. Content analysis was performed and the contents of each page were categorized by the tone of the post (positive, negative or neutral). Then, a one-year follow-up search was conducted to compare the contents. Twelve Facebook pages each were initially identified for cannabis and for kratom. Follower numbers were higher for cannabis pages. Kratom pages were less active but were open for a longer time. Posts with positive tones and neutral tones were found for both drugs, but none had negative tones. Other drugs were mentioned on the cannabis pages, but they were different from those mentioned on the kratom pages. Issues regarding drug legalization were found on the cannabis pages but not on the kratom pages during the searching period. One year later, the tone of the posts was in the same direction, but the page activity had increased. The information currently available on the sampled Facebook pages was positive towards the use of cannabis and kratom. No information about harm from these drugs was found through our search.

Analysis of Potential Glove-Induced Hand Injury Metrics During Typical Neutral Buoyancy Training Operations

NASA Technical Reports Server (NTRS)

McFarland, Shane

2016-01-01

Injuries to the hands are common among astronauts who train for extravehicular activity. When the gloves are pressurized, they restrict movement and create pressure points during tasks, sometimes resulting in pain, muscle fatigue, abrasions, and occasionally more severe injuries such as onycholysis. A brief review of NASA's Lifetime Surveillance of Astronaut Health's injury database reveals that 76 percent of astronaut hand and arm injuries from training between 1993 and 2010 occurred either to the fingernail, finger crotch, metacarpophalangeal joint, or fingertip. The purpose of this study was to assess the potential of using small sensors to measure forces acting on the fingers and hand within pressurized gloves and other variables such as skin temperature, humidity, and fingernail strain of a NASA crewmember during typical NBL (Neutral Buoyancy Laboratory) training activity. During the 5-hour exercise, the crewmember seemed to exhibit very large forces on some fingers, resulting in higher strain than seen in previous glove-box testing. In addition, vital information was collected on the glove cavity environment with respect to temperature and humidity. All of this information gathered during testing will be carried forward into future testing, potentially in glove-box- or 1G- (1 gravitational force) or NBL-suited environments, to better characterize and understand the possible causes of hand injury amongst NASA crew.

Emotions and stress increase respiratory resistance in asthma.

PubMed

Ritz, T; Steptoe, A; DeWilde, S; Costa, M

2000-01-01

Clinical reports suggest that various emotions and types of stress can precipitate asthmatic symptoms, but there is little experimental evidence to substantiate this claim. We studied the impact of different emotional states and stress on respiratory resistance in asthmatic and nonasthmatic individuals. Participants (24 asthmatic and 24 nonasthmatic patients) viewed short film sequences selected to induce anxiety, anger, depression, elation, happiness, contentment, or a neutral affective state and completed two stressful tasks, mental arithmetic to induce active coping efforts and viewing of medical slides to induce passive coping efforts. Oscillatory resistance, heart rate, blood pressure, baroreflex sensitivity, skin conductance level, respiration rate and volume, and self-reported affective state were measured throughout the session. Uniform increases in oscillatory resistance were found in all emotional states compared with the neutral state and during mental arithmetic in both groups. Asthmatic patients showed stronger reactions to the medical slides than healthy control subjects, with significant increases in oscillatory resistance, blood pressure, skin conductance level, and minute volume, as well as higher levels of self-reported depression, arousal, and shortness of breath. Changes in oscillatory resistance were inconsistently correlated with other physiological indices. Various emotional states and stress increase oscillatory resistance largely independently of concurrent increases in autonomic or ventilatory activity. The particular sensitivity of asthmatics to passive coping demand requires additional research.

Landfills as sources of polyfluorinated compounds, polybrominated diphenyl ethers and musk fragrances to ambient air

NASA Astrophysics Data System (ADS)

Weinberg, Ingo; Dreyer, Annekatrin; Ebinghaus, Ralf

2011-02-01

In order to investigate landfills as sources of polyfluorinated compounds (PFCs), polybrominated diphenyl ethers (PBDEs) and synthetic musk fragrances to the atmosphere, air samples were simultaneously taken at two landfills (one active and one closed) and two reference sites using high volume air samplers. Contaminants were accumulated on glass fiber filters (particle phase) and PUF/XAD-2/PUF cartridges (gas phase), extracted by methyl-tert butyl ether/acetone (neutral PFCs), methanol (ionic PFCs) or hexane/acetone (PBDEs, musk fragrances), and detected by GC-MS (neutral PFCs, PBDEs, musk fragrances) or HPLC-MS/MS (ionic PFCs). Total concentrations ranged from 84 to 706 pg m -3 (volatile PFCs, gas phase), from

Mathematical Modelling of Arctic Polygonal Tundra with Ecosys: 2. Microtopography Determines How CO2 and CH4 Exchange Responds to Changes in Temperature and Precipitation

NASA Astrophysics Data System (ADS)

Grant, R. F.; Mekonnen, Z. A.; Riley, W. J.; Arora, B.; Torn, M. S.

2017-12-01

Differences of surface elevation in arctic polygonal landforms cause spatial variation in soil water contents (θ), active layer depths (ALD), and thereby in CO2 and CH4 exchange. Here we test hypotheses in ecosys for topographic controls on CO2 and CH4 exchange in trough, rim, and center features of low- and flat-centered polygons (LCP and FCP) against chamber and eddy covariance (EC) measurements during 2013 at Barrow, Alaska. Larger CO2 influxes and CH4 effluxes were measured with chambers and modeled with ecosys in LCPs than in FCPs and in lower features (troughs) than in higher (rims) within LCPs and FCPs. Spatially aggregated CO2 and CH4 fluxes from ecosys were significantly correlated with EC flux measurements. Lower features were modeled as C sinks (52-56 g C m-2 yr-1) and CH4 sources (4-6 g C m-2 yr-1), and higher features as near C neutral (-2-15 g C m-2 yr-1) and CH4 neutral (0.0-0.1 g C m-2 yr-1). Much of the spatial and temporal variations in CO2 and CH4 fluxes were modeled from topographic effects on water and snow movement and thereby on θ, ALD, and soil O2 concentrations. Model results forced with meteorological data from 1981 to 2015 indicated increasing net primary productivity in higher features and CH4 emissions in some lower and higher features since 2008, attributed mostly to recent rises in precipitation. Small-scale variation in surface elevation causes large spatial variation of greenhouse gas (GHG) exchanges and therefore should be considered in estimates of GHG exchange in polygonal landscapes.

Joint positions matter for ultrasound examination of RA patients-increased power Doppler signal in neutral versus flat position of hands.

PubMed

Husic, Rusmir; Lackner, Angelika; Stradner, Martin H; Hermann, Josef; Dejaco, Christian

2017-08-01

Position of joints might influence the result of US examination in patients with RA. The purpose of this work was to compare grey-scale (GS) and power Doppler (PWD) findings obtained in neutral vs flat position of hands. A cross-sectional study of 42 RA patients with active disease. Two dimensional and 3D sonography of wrists and MCP joints were conducted in two different joint positions: neutral position, which is a slight flexion of the fingers with relaxed extensor muscles; and flat position, where all palm and volar sides of fingers touch the Table. Two dimensional GS synovitis (GSS) and PWD signals were scored semi-quantitatively (0-3). For 3D sonography, the percentage of PWD voxels within a region of interest was calculated. GSS was not quantified using 3D sonography. Compared with neutral position, 2D PWD signals disappeared in 28.3% of joints upon flattening. The median global 2D PWD score (sum of all PWD scores of an individual patient) decreased from 8 to 3 ( P < 0.001), and the global 3D PWD voxel score from 3.8 to 0.9 ( P < 0.001). The reduction of PWD scores was similar in all joints (2D: minus 50%, 3D: minus 66.4-80.1%). Inter- and intrareader agreement of PWD results was good (intraclass correlation coefficient: 0.75-0.82). In RA, a neutral position of the hands is linked to a higher sensitivity of 2D and 3D sonography in detecting PWD signals at wrists and MCP joints, compared with a flat position. Standardization of the scanning procedure is essential for obtaining comparable US results in RA patients in trials and clinical routines. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Effects of task-irrelevant emotional stimuli on working memory processes in mild cognitive impairment.

PubMed

Berger, Christoph; Erbe, Anna-Katharina; Ehlers, Inga; Marx, Ivo; Hauenstein, Karlheinz; Teipel, Stefan

2015-01-01

Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.

Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

PubMed Central

deCamp, Allan; Hraber, Peter; Bailer, Robert T.; Seaman, Michael S.; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; Gorny, Miroslaw K.; Zolla-Pazner, Susan; LaBranche, Celia C.; Mascola, John R.; Korber, Bette T.

2014-01-01

ABSTRACT Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env.IMC.LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. IMPORTANCE An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies. Efforts to elicit broadly cross-reactive neutralizing antibodies that will protect against infection by most circulating strains of the virus are guided in part by in vitro assays that determine the ability of vaccine-elicited antibodies to neutralize genetically diverse HIV-1 variants. Until now, little information was available on how many and which strains of the virus are best suited for this purpose. We applied robust statistical methods to evaluate a large neutralization data set and identified a small panel of viruses that are a good representation of the global epidemic. The neutralization properties of this new panel of reference strains should facilitate the development of an effective HIV-1 vaccine. PMID:24352443

Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies.

PubMed

deCamp, Allan; Hraber, Peter; Bailer, Robert T; Seaman, Michael S; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; Gorny, Miroslaw K; Zolla-Pazner, Susan; LaBranche, Celia C; Mascola, John R; Korber, Bette T; Montefiori, David C

2014-03-01

Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env.IMC.LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies. Efforts to elicit broadly cross-reactive neutralizing antibodies that will protect against infection by most circulating strains of the virus are guided in part by in vitro assays that determine the ability of vaccine-elicited antibodies to neutralize genetically diverse HIV-1 variants. Until now, little information was available on how many and which strains of the virus are best suited for this purpose. We applied robust statistical methods to evaluate a large neutralization data set and identified a small panel of viruses that are a good representation of the global epidemic. The neutralization properties of this new panel of reference strains should facilitate the development of an effective HIV-1 vaccine.

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women.

PubMed

Li, Bingbing; Cheng, Gang; Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects' Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability.

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women

PubMed Central

Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects’ Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability. PMID:27977692

Threat distractor and perceptual load modulate test-retest reliability of anterior cingulate cortex response.

PubMed

Bunford, Nora; Kinney, Kerry L; Michael, Jamie; Klumpp, Heide

2017-07-03

Accumulating data from fMRI studies implicate the rostral anterior cingulate cortex (rACC) in inhibition of attention to threat distractors that compete with task-relevant goals for processing resources. However, little data is available on the reliability of rACC activation. Our aim in the current study was to examine test-retest reliability of rACC activation over a 12-week period, in the context of a validated emotional interference paradigm that varied in perceptual load. During functional MRI, 23 healthy volunteers completed a task involving a target letter in a string of identical letters (low load) or in a string of mixed letters (high load) superimposed on angry, fearful, and neutral face distractors. Intraclass correlation coefficients (ICCs) indicated that under low, but not high perceptual load, rACC activation to fearful vs. neutral distractors was moderately reliable. Conversely, regardless of perceptual load, rACC activation to angry vs. neutral distractors was not reliable. Regarding behavioral performance, ICCs indicated that accuracy was not reliable regardless of distractor type or perceptual load. Although reaction time (RT) was similarly not reliable regardless of distractor type under low perceptual load, RT to angry vs. neutral distractors and to fearful vs. neutral distractors was reliable under high perceptual load. Together, results indicate the test-retest reliability of rACC activation and corresponding behavioral performance are context dependent; reliability of the former varies as a function of distractor type and level of cognitive demand, whereas reliability of the latter depends on behavioral index (accuracy vs. RT) and level of cognitive demand but not distractor type. Copyright © 2017 Elsevier Inc. All rights reserved.

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies.

PubMed

Xu, Chun; Goß, Annika Verena; Dorneburg, Carmen; Debatin, Klaus-Michael; Wei, Jiwu; Beltinger, Christian

2018-01-01

Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID 50 ) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. We prove the principle that a non-replicating OMV can serve as a "decoy" for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV.

Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder

PubMed Central

Britton, Jennifer C.; Stewart, S. Evelyn; Killgore, William D.S.; Rosso, Isabelle M.; Price, Lauren M.; Gold, Andrea L.; Pine, Daniel S.; Wilhelm, Sabine; Jenike, Michael A.; Rauch, Scott L.

2010-01-01

Background Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation (Cannistraro et al., 2004). Methods In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a healthy comparison sample (HC, N=17) performed a gender discrimination task while viewing emotional faces (happy, fear, disgust) and neutral faces. Results Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. Conclusions Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder-specific. PMID:20602430

Bovine coronavirus (BCV) infections in transported commingled beef cattle and sole-source ranch calves

PubMed Central

Fulton, Robert W.; Step, Douglas L.; Wahrmund, Jackie; Burge, Lurinda J.; Payton, Mark E.; Cook, Billy J.; Burken, Dirk; Richards, Chris J.; Confer, Anthony W.

2011-01-01

This study investigated bovine coronavirus (BCV) in both beef calves direct from the ranch and commingled, mixed-source calves obtained from an auction market. The level of BCV-neutralizing antibodies found in the calves varied among ranches in 2 different studies in a retained-ownership program (ROP), from the ranch to the feedlot. Calves with low levels of BCV-neutralizing antibodies (16 or less) were more likely to be treated for bovine respiratory disease (BRD) than those with higher titers. In 3 studies of commingled, mixed-source calves, BCV was recovered from calves at entry to the feedlot and the infections were cleared by day 8. The BCV was identified in lung samples [bronchoalveolar lavage (BAL) collection] as well as in nasal swabs. Calves with low levels of BCV-neutralizing antibodies at entry were most likely to be shedding BCV. Bovine coronavirus was isolated from both healthy and sick calves, but not from sick calves after 4 d arrival at the feedlot. Bovine coronavirus (BCV) should be considered along with other bovine respiratory viruses in the diagnosis of etiologies in bovine respiratory disease, especially for animals that become sick shortly after arrival. If approved vaccines are developed, it would be best to carry out vaccination programs before calves are weaned, giving them sufficient time to gain active immunity before commingling with other cattle. PMID:22210995

Polar silica-based stationary phases. Part II- Neutral silica stationary phases with surface bound maltose and sorbitol for hydrophilic interaction liquid chromatography.

PubMed

Rathnasekara, Renuka; El Rassi, Ziad

2017-07-28

Two neutral polyhydroxylated silica bonded stationary phases, namely maltose-silica (MALT-silica) and sorbitol-silica (SOR-silica), have been introduced and chromatographically characterized in hydrophilic interaction liquid chromatography (HILIC) for a wide range of polar compounds. The bonding of the maltose and sorbitol to the silica surface was brought about by first converting bare silica to an epoxy-activated silica surface via reaction with γ-glycidoxypropyltrimethoxysilane (GPTMS) followed by attaching maltose and sorbitol to the epoxy surface in the presence of the Lewis acid catalyst BF 3 .ethereate. Both silica based columns offered the expected retention characteristics usually encountered for neutral polar surface. The retention mechanism is majorly based on solute' differential partitioning between an organic rich hydro-organic mobile phase (e.g., ACN rich mobile phase) and an adsorbed water layer on the surface of the stationary phase although additional hydrogen bonding was also responsible in some cases for solute retention. The MALT-silica column proved to be more hydrophilic and offered higher retention, separation efficiency and resolution than the SOR-silica column among the tested polar solutes such as derivatized mono- and oligosaccharides, weak phenolic acids, cyclic nucleotide monophosphate and nucleotide-5'-monophosphates, and weak bases, e.g., nucleobases and nucleosides. Copyright © 2017 Elsevier B.V. All rights reserved.

Digital genome-wide ncRNA expression, including SnoRNAs, across 11 human tissues using polyA-neutral amplification.

PubMed

Castle, John C; Armour, Christopher D; Löwer, Martin; Haynor, David; Biery, Matthew; Bouzek, Heather; Chen, Ronghua; Jackson, Stuart; Johnson, Jason M; Rohl, Carol A; Raymond, Christopher K

2010-07-26

Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available.

Electric fields measured by ISEE-1 within and near the neutral sheet during quiet and active times

NASA Technical Reports Server (NTRS)

Cattell, C. A.; Mozer, F. S.

1982-01-01

An understanding of the physical processes occurring in the magnetotail and plasmasheet during different interplanetary magnetic field orientations and differing levels of ground magnetic activity is crucial for the development of a theory of energy transfer from the solar wind to the particles which produce auroral arcs. In the present investigation, the first observations of electric fields during neutral sheet crossings are presented, taking into account the statistical correlations of the interplanetary magnetic field direction and ground activity with the character of the electric field. The electric field data used in the study were obtained from a double probe experiment on the ISEE-1 satellite. The observations suggest that turbulent electric and magnetic fields are intimately related to plasma acceleration in the neutral sheet and to the processes which create auroral particles.

[Advance in research on regulatory mechanism and functions of neutral sphingomyelinse 2].

PubMed

Zhang, Lan; Guo, Jun

2013-10-01

Neutral sphingomyelinase 2 (nSMase2), which located mainly on the plasma membrane, hydrolyzes sphingomyelin into ceramide and plays an important role in the physiological and pathological regulation of cell apoptosis, cell growth arrest, and inflammation. nSMase2 is also involved in the development of Alzheimer's disease and the bone growth.Under neutral pH and the presence of Ca(2+), Mg(2+), and Mn(+), the activity of nSMase2 is induced by oxidative stress through phosphorylation. Furthermore, the induced interaction of anionic phospholipids and the signaling molecules like receptor for activated C-kinase 1/embryonic ectodermal development with nSMase2 are also crucial mechanisms of protein activation. In the review, recent research advances in the structure and function of nSMase2 and its underlying mechanisms are summarized.

Comparison of nutritional compositions and antioxidant activities of building blocks in shinseoncho and kale green vegetable juices.

PubMed

Kim, Seong Yeong

2012-12-01

Shinseoncho and kale were divided into stem [shinseoncho stems (SS) and kale stems (KS)] and leaf parts [shinseoncho leaves (SL) and kale leaves (KL)] and made into green vegetable juices for analyses of nutritional compositions and antioxidant activities. Higher values of total acidity were observed in SL (0.736%) and KL (0.841%) than in SS (0.417%) and KS (0.335%) (p<0.05). Neutral sugar content showed higher values in SS (21.740 mg/mL) and SL (18.657 mg/mL) when compared with KS (1.497 mg/mL) and KL (1.452 mg/mL) (p<0.05). Protein content showed the highest value in SL (7.610 mg/mL) (p<0.05), while SS (0.403 mg/mL) and KS (0.403 mg/mL) showed similar lower values. Total polyphenol contents of SL (423.139 μg/mL) was significantly higher value (p<0.05) than those of other samples, which occurred in the following order: SL> KL (218.494 μg/mL)> KS (107.269 μg/mL)> SS (75.894 μg/mL). KL exerted the highest DPPH radical scavenging activity (84.834%) (p<0.05), which occurred in the following order: KL> SL (63.473%)> KS (52.894%)> SS (35.443%). ABTS radical scavenging activity showed that SL (66.088%) and KL (38.511%) had higher scavenging activities, whereas SS (7.695%) and KS (9.609%) demonstrated to be lower activities (p<0.05). In general, leaf parts had much higher antioxidant activities as well as total polyphenol contents than those of the stem parts. In conclusion, shinseoncho and kale, particularly their leaf parts, offer antioxidant properties in green vegetable juices and the consumption of them may be beneficial as a nutrition source and in health protection.

Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments

DOE PAGES

Hraber, Peter; Rademeyer, Cecilia; Williamson, Carolyn; ...

2017-07-26

In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus panels, chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses from early infection. All 200 Envs were expressed as a single round of replication pseudoviruses and were tested to quantify neutralization titers by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C infections. We selected large panels of 50 and 100 Envsmore » either to characterize cross-reactive breadth for sera identified as having potent neutralization activity based on initial screening or to evaluate neutralization magnitude-breadth distributions of newly isolated antibodies. We identified these panels by downselection after hierarchical clustering of bnAb neutralization titers. The resulting panels represent the diversity of neutralization profiles throughout the range of virus sensitivities identified in the original panel of 200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials or natural-infection studies for neutralization responses. We considered panels selected by previously described methods but favored a computationally informed method that enabled selection of viruses representing diverse neutralization sensitivity patterns, given that we do nota prioriknow what the neutralization-response profile of vaccine sera will be relative to that of sera from infected individuals. The resulting 12-Env panel complements existing panels. Use of standardized panels enables direct comparisons of data from different trials and study sites testing HIV-1 clade C-specific products. HIV-1 group M includes nine clades and many recombinants. Clade C is the most common lineage, responsible for roughly half of current HIV-1 infections, and is a focus for vaccine design and testing. Standard reference reagents, particularly virus panels to study neutralization by antibodies, are crucial for developing cost-effective and yet rigorous and reproducible assays against diverse examples of this variable virus. We developed clade C-specific panels for use as standardized reagents to monitor complex polyclonal sera for neutralization activity and to characterize the potency and breadth of cross-reactive neutralization by monoclonal antibodies, whether engineered or isolated from infected individuals. We chose from 200 southern African, clade C envelope-pseudotyped viruses with neutralization titers against 16 broadly neutralizing antibodies and 30 sera from chronic clade C infections. We selected panels to represent the diversity of bnAb neutralization profiles and Env neutralization sensitivities. Finally, use of standard virus panels can facilitate comparison of results across studies and sites.« less

Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments

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

Hraber, Peter; Rademeyer, Cecilia; Williamson, Carolyn

In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus panels, chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses from early infection. All 200 Envs were expressed as a single round of replication pseudoviruses and were tested to quantify neutralization titers by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C infections. We selected large panels of 50 and 100 Envsmore » either to characterize cross-reactive breadth for sera identified as having potent neutralization activity based on initial screening or to evaluate neutralization magnitude-breadth distributions of newly isolated antibodies. We identified these panels by downselection after hierarchical clustering of bnAb neutralization titers. The resulting panels represent the diversity of neutralization profiles throughout the range of virus sensitivities identified in the original panel of 200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials or natural-infection studies for neutralization responses. We considered panels selected by previously described methods but favored a computationally informed method that enabled selection of viruses representing diverse neutralization sensitivity patterns, given that we do nota prioriknow what the neutralization-response profile of vaccine sera will be relative to that of sera from infected individuals. The resulting 12-Env panel complements existing panels. Use of standardized panels enables direct comparisons of data from different trials and study sites testing HIV-1 clade C-specific products. HIV-1 group M includes nine clades and many recombinants. Clade C is the most common lineage, responsible for roughly half of current HIV-1 infections, and is a focus for vaccine design and testing. Standard reference reagents, particularly virus panels to study neutralization by antibodies, are crucial for developing cost-effective and yet rigorous and reproducible assays against diverse examples of this variable virus. We developed clade C-specific panels for use as standardized reagents to monitor complex polyclonal sera for neutralization activity and to characterize the potency and breadth of cross-reactive neutralization by monoclonal antibodies, whether engineered or isolated from infected individuals. We chose from 200 southern African, clade C envelope-pseudotyped viruses with neutralization titers against 16 broadly neutralizing antibodies and 30 sera from chronic clade C infections. We selected panels to represent the diversity of bnAb neutralization profiles and Env neutralization sensitivities. Finally, use of standard virus panels can facilitate comparison of results across studies and sites.« less

Acidic hyaluronidase activity is present in mouse sperm and is reduced in the absence of SPAM1: Evidence for a Role for Hyaluronidase 3 in mouse and human sperm

PubMed Central

Reese, Kristen L.; Aravindan, Rolands G.; Griffiths, Genevieve S.; Shao, Minghai; Wang, Yipei; Galileo, Deni S.; Atmuri, Vasantha; Triggs-Raine, Barbara L.; Martin-DeLeon, Patricia A.

2010-01-01

The molecular mechanisms underlying sperm penetration of the physical barriers surrounding the oocyte have not been completely delineated. Although neutral-active or “reproductive” hyaluronidases (hyases), exemplified by Sperm Adhesion Molecule 1 (SPAM1), are thought to be responsible for hyaluronan digestion in the egg vestments and for sperm-zona binding, their roles in mouse sperm have been recently questioned. Here we report that acidic “somatic” Hyaluronidase 3 (HYAL3) exists in two isoforms in human (~47 kDa, ~55 kDa) and mouse (~44, ~47kDa) sperm where it resides on the plasma membrane over the head and midpiece. Mouse isoforms are differentially distributed in the soluble (SAP), membrane (MBP), and acrosome-reacted (AR) fraction where they are most abundant. Comparisons of zymography of Hyal3 null and wild-type (WT) AR and MBP fractions show significant HYAL3 activity at pH 3 and 4, and less at 7. At pH 4, a second acid-active hyase band at ~57 kDa is present in the AR fraction. HYAL3 activity was confirmed using immunoprecipitated HYAL3 and spectrophotometry. In total proteins, hyase activity was higher at pH 6 than at 4 where Spam1 nulls had significantly (P<0.01) diminished activity, indicating that murine SPAM1 has acidic activity. Although fully fertile, Hyal3 null sperm showed delayed cumulus penetration and reduced acrosomal exocytosis. HYAL3, similar to SPAM1 with which it shares 74.6% structural similarity, exists in epididymal tissue/fluid from which it is acquired by caudal mouse sperm in vitro. Our results indicate for the first time the concerted activity of both neutral- and acid-active hyaluronidases in sperm. PMID:20586096

Evaluation of smallpox vaccines using variola neutralization

PubMed Central

Damon, Inger K.; Davidson, Whitni B.; Hughes, Christine M.; Olson, Victoria A.; Smith, Scott K.; Holman, Robert C.; Frey, Sharon E.; Newman, Frances; Belshe, Robert B.; Yan, Lihan; Karem, Kevin

2009-01-01

The search for a ‘third’-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific ‘in vitro’ activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination. PMID:19339477

The Joint Contribution of Activation and Inhibition in Moderating Carryover Effects of Anger on Social Judgment

PubMed Central

Fiori, Marina; Shuman, Vera

2017-01-01

Carryover effects of emotions that lead to biases in social judgments are commonly observed. We suggest that such effects may be influenced by the ability to engage or disengage attention from emotional stimuli. We assessed the ability to activate and inhibit attention to anger stimuli, experimentally induced anger in a demanding task, and measured social judgment toward an ambiguous target. Results show that higher activation and higher inhibition of anger-related information predicted more biased evaluations of the ambiguous target when individuals were experiencing anger, but not in an emotionally neutral condition. Interestingly, the effect of activation and inhibition in the anger condition emerged only when such variables were entered simultaneously in the regression model, indicating that they had an additive effect in predicting carryover effects of anger on social judgement. Results are consistent with a cooperative suppression effect (Conger, 1974) of activation and inhibition and may be explained by either an increased accessibility of anger-related cues leading to more biased social judgments, or by an instance in which being good at engaging in and disengaging attention from emotional cues might have depleted participants’ resources making carryover effects of anger more likely to occur. Ultimately, the finding highlight that individual differences in attentional processes are important moderators for carryover effects of emotions. PMID:28993743

Prevalence of Neutralizing Antibodies to Japanese Encephalitis Virus among High-Risk Age Groups in South Korea, 2010

PubMed Central

Ju, Young Ran; Han, Myung Guk; Lee, Won-Ja; Jeong, Young Eui

2016-01-01

After an extensive vaccination policy, Japanese encephalitis (JE) was nearly eliminated since the mid-1980s in South Korea. Vaccination in children shifted the affected age of JE patients from children to adults. However, an abrupt increase in JE cases occurred in 2010, and this trend has continued. The present study aimed to investigate the prevalence of neutralizing antibodies to the JE virus (JEV) among high-risk age groups (≥40 years) in South Korea. A plaque reduction neutralization test was conducted to evaluate the prevalence of neutralizing antibodies to JEV in 945 subjects within four age groups (30–39, 40–49, 50–59, and 60–69 years) in 10 provinces. Of the 945 enrolled subjects, 927 (98.1%) exhibited antibodies against JEV. No significant differences were found in the prevalence of neutralizing antibodies according to sex, age, or occupation. However, there were significant differences in the plaque reduction rate according to age and occupation; oldest age group had a higher reduction rate, and subjects who were employed in agriculture or forestry also had a higher value than the other occupations. We also found that three provinces (Gangwon, Jeonnam, and Gyeongnam) had a relatively lower plaque reduction rate than the other locations. In addition, enzyme-linked immunosorbent assays were conducted to determine recent viral infections and 12 (2.2%) subjects were found to have been recently infected by the virus. In conclusion, the present study clearly indicated that the prevalence of neutralizing antibodies has been maintained at very high levels among adult age groups owing to vaccination or natural infections, or both. In the future, serosurveillance should be conducted periodically using more representative samples to better understand the population-level immunity to JE in South Korea. PMID:26807709

If F(ST) does not measure neutral genetic differentiation, then comparing it with Q(ST) is misleading. Or is it?

PubMed

Edelaar, Pim; Björklund, Mats

2011-05-01

The comparison between neutral genetic differentiation (F(ST) ) and quantitative genetic differentiation (Q(ST) ) is commonly used to test for signatures of selection in population divergence. However, there is an ongoing discussion about what F(ST) actually measures, even resulting in some alternative metrics to express neutral genetic differentiation. If there is a problem with F(ST) , this could have repercussions for its comparison with Q(ST) as well. We show that as the mutation rate of the neutral marker increases, F(ST) decreases: a higher within-population heterozygosity (He) yields a lower F(ST) value. However, the same is true for Q(ST) : a higher mutation rate for the underlying QTL also results in a lower Q(ST) estimate. The effect of mutation rate is equivalent in Q(ST) and F(ST) . Hence, the comparison between Q(ST) and F(ST) remains valid, if one uses neutral markers whose mutation rates are not too high compared to those of quantitative traits. Usage of highly variable neutral markers such as hypervariable microsatellites can lead to serious biases and the incorrect inference that divergent selection has acted on populations. Much of the discussion on F(ST) seems to stem from the misunderstanding that it measures the differentiation of populations, whereas it actually measures the fixation of alleles. In their capacity as measures of population differentiation, Hedrick's G'(ST) and Jost's D reach their maximum value of 1 when populations do not share alleles even when there remains variation within populations, which invalidates them for comparisons with Q(ST) . © 2011 Blackwell Publishing Ltd.