Inhibition of the ATPase from Halobacterium Saccharovorum by Thiol Inhibitors: Evidence for the Presence of More Than One Essential Cysteinyl Residue

NASA Technical Reports Server (NTRS)

Hochstein, Lawrence I.; Emrich, Errol; Stan-Lotter, Helga; DeVincenzi, Donald L. (Technical Monitor)

1995-01-01

The vacuolar-like ATPase from Halobacterium saccha vorum is inhibited by N-ethylmaleimide and p-chloromercudphenylsulfonate. The failure of adenine nucleotides to protect against p-chloromercuriphenyisulfonate inhibition, of p-chloromercuriphenylsulfonate to protect against N-ethylmaleimide inhibition, and the difference in the temperature dependence of inactivation infers that the enzyme contains at least two thiols that are essential for enzyme activity. CNBr cleavage of C-14-N-ethylmaleimide labeled subunit results in two radioactive peptides that locates the N-ethylmaleimide-reactive cysteinyl residue as cysteine-262 in the H. salinarium sequence.

In Vitro Reconstitution of Autophagosome-Lysosome Fusion.

PubMed

Diao, J; Li, L; Lai, Y; Zhong, Q

2017-01-01

SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) proteins are a highly regulated class of membrane proteins lying in the center of membrane fusion. In conjunction with accessory proteins, SNAREs drive efficient merger of two distinct lipid bilayers into one interconnected structure. This chapter describes our fluorescence resonance energy transfer (FRET)-based proteoliposome fusion assays for the roles of various SNARE proteins, accessory proteins, and effects of different lipid compositions on membrane fusion involved in autophagy. © 2017 Elsevier Inc. All rights reserved.

NemR Is a Bleach-sensing Transcription Factor*

PubMed Central

Gray, Michael J.; Wholey, Wei-Yun; Parker, Benjamin W.; Kim, Minwook; Jakob, Ursula

2013-01-01

Hypochlorous acid (HOCl), the active component of household bleach, also functions as a powerful antimicrobial during the innate immune response. Despite its widespread use, surprisingly little is known about how cells sense or respond to HOCl. We now demonstrate that Escherichia coli NemR is a redox-regulated transcriptional repressor, which uses the oxidation status of HOCl-sensitive cysteine residues to respond to bleach and related reactive chlorine species. NemR controls bleach-mediated expression of two enzymes required for detoxification of reactive electrophiles: glyoxalase I and N-ethylmaleimide reductase. Both enzymes contribute to bacterial bleach survival. These results provide evidence that bleach resistance relies on the capacity of organisms to specifically sense reactive chlorine species and respond with the up-regulation of enzymes dedicated to detoxification of methylglyoxal and other reactive electrophiles. PMID:23536188

Examining the latent structure of anxiety sensitivity in adolescents using factor mixture modeling.

PubMed

Allan, Nicholas P; MacPherson, Laura; Young, Kevin C; Lejuez, Carl W; Schmidt, Norman B

2014-09-01

Anxiety sensitivity has been implicated as an important risk factor, generalizable to most anxiety disorders. In adults, factor mixture modeling has been used to demonstrate that anxiety sensitivity is best conceptualized as categorical between individuals. That is, whereas most adults appear to possess normative levels of anxiety sensitivity, a small subset of the population appears to possess abnormally high levels of anxiety sensitivity. Further, those in the high anxiety sensitivity group are at increased risk of having high levels of anxiety and of having an anxiety disorder. This study was designed to determine whether these findings extend to adolescents. Factor mixture modeling was used to examine the best fitting model of anxiety sensitivity in a sample of 277 adolescents (M age = 11.0 years, SD = 0.81). Consistent with research in adults, the best fitting model consisted of 2 classes, 1 containing adolescents with high levels of anxiety sensitivity (n = 25) and another containing adolescents with normative levels of anxiety sensitivity (n = 252). Examination of anxiety sensitivity subscales revealed that the social concerns subscale was not important for classification of individuals. Convergent and discriminant validity of anxiety sensitivity classes were found in that membership in the high anxiety sensitivity class was associated with higher mean levels of anxiety symptoms, controlling for depression and externalizing problems, and was not associated with higher mean levels of depression or externalizing symptoms controlling for anxiety problems. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Examining the Latent Structure of Anxiety Sensitivity in Adolescents using Factor Mixture Modeling

PubMed Central

Allan, Nicholas P.; MacPherson, Laura; Young, Kevin C.; Lejuez, Carl W.; Schmidt, Norman B.

2014-01-01

Anxiety sensitivity has been implicated as an important risk factor, generalizable to most anxiety disorders. In adults, factor mixture modeling has been used to demonstrate that anxiety sensitivity is best conceptualized as categorical between individuals. That is, whereas most adults appear to possess normative levels of anxiety sensitivity, a small subset of the population appears to possess abnormally high levels of anxiety sensitivity. Further, those in the high anxiety sensitivity group are at increased risk of having high levels of anxiety and of having an anxiety disorder. This study was designed to determine whether these findings extend to adolescents. Factor mixture modeling was used to examine the best fitting model of anxiety sensitivity in a sample of 277 adolescents (M age = 11.0, SD = .81). Consistent with research in adults, the best fitting model consisted of two classes, one containing adolescents with high levels of anxiety sensitivity (n = 25), and another containing adolescents with normative levels of anxiety sensitivity (n = 252). Examination of anxiety sensitivity subscales revealed that the social concerns subscale was not important for classification of individuals. Convergent and discriminant validity of anxiety sensitivity classes were found in that membership in the high anxiety sensitivity class was associated with higher mean levels of anxiety symptoms, controlling for depression and externalizing problems, and was not associated with higher mean levels of depression or externalizing symptoms controlling for anxiety problems. PMID:24749756

RF-MEMS Load Sensors with Enhanced Q-factor and Sensitivity in a Suspended Architecture.

PubMed

Melik, Rohat; Unal, Emre; Perkgoz, Nihan Kosku; Puttlitz, Christian; Demir, Hilmi Volkan

2011-03-01

In this paper, we present and demonstrate RF-MEMS load sensors designed and fabricated in a suspended architecture that increases their quality-factor (Q-factor), accompanied with an increased resonance frequency shift under load. The suspended architecture is obtained by removing silicon under the sensor. We compare two sensors that consist of 195 μm × 195 μm resonators, where all of the resonator features are of equal dimensions, but one's substrate is partially removed (suspended architecture) and the other's is not (planar architecture). The single suspended device has a resonance of 15.18 GHz with 102.06 Q-factor whereas the single planar device has the resonance at 15.01 GHz and an associated Q-factor of 93.81. For the single planar device, we measured a resonance frequency shift of 430 MHz with 3920 N of applied load, while we achieved a 780 MHz frequency shift in the single suspended device. In the planar triplet configuration (with three devices placed side by side on the same chip, with the two outmost ones serving as the receiver and the transmitter), we observed a 220 MHz frequency shift with 3920 N of applied load while we obtained a 340 MHz frequency shift in the suspended triplet device with 3920 N load applied. Thus, the single planar device exhibited a sensitivity level of 0.1097 MHz/N while the single suspended device led to an improved sensitivity of 0.1990 MHz/N. Similarly, with the planar triplet device having a sensitivity of 0.0561 MHz/N, the suspended triplet device yielded an enhanced sensitivity of 0.0867 MHz/N.

Loss of a membrane trafficking protein αSNAP induces non-canonical autophagy in human epithelia

PubMed Central

Naydenov, Nayden G.; Harris, Gianni; Morales, Victor; Ivanov, Andrei I.

2012-01-01

Autophagy is a catabolic process that sequesters intracellular proteins and organelles within membrane vesicles called autophagosomes with their subsequent delivery to lyzosomes for degradation. This process involves multiple fusions of autophagosomal membranes with different vesicular compartments; however, the role of vesicle fusion in autophagosomal biogenesis remains poorly understood. This study addresses the role of a key vesicle fusion regulator, soluble N-ethylmaleimide-sensitive factor attachment protein α (αSNAP), in autophagy. Small interfering RNA-mediated downregulation of αSNAP expression in cultured epithelial cells stimulated the autophagic flux, which was manifested by increased conjugation of microtubule-associated protein light chain 3 (LC3-II) and accumulation of LC3-positive autophagosomes. This enhanced autophagy developed via a non-canonical mechanism that did not require beclin1-p150-dependent nucleation, but involved Atg5 and Atg7-mediated elongation of autophagosomal membranes. Induction of autophagy in αSNAP-depleted cells was accompanied by decreased mTOR signaling but appeared to be independent of αSNAP-binding partners, N-ethylmaleimide-sensitive factor and BNIP1. Loss of αSNAP caused fragmentation of the Golgi and downregulation of the Golgi-specific GTP exchange factors, GBF1, BIG1 and BIG2. Pharmacological disruption of the Golgi and genetic inhibition of GBF1 recreated the effects of αSNAP depletion on the autophagic flux. Our study revealed a novel role for αSNAP as a negative regulator of autophagy that acts by enhancing mTOR signaling and regulating the integrity of the Golgi complex. PMID:23187805

Simultaneous determination of azathioprine and 6-mercaptopurine in serum by reversed-phase high-performance liquid chromatography.

PubMed

Tsutsumi, K; Otsuki, Y; Kinoshita, T

1982-09-10

The simultaneous determination of azathioprine and its metabolite 6-mercaptopurine in serum by reversed-phase high-performance liquid chromatography is described. 6-Mercaptopurine was converted to a derivative, 6-mercaptopurine-N-ethylmaleimide, which is stable against autoxidation, on reaction with N-ethylmaleimide. Since the N-ethylmaleimide derivative was more hydrophobic than the parent compound, it could be extracted into ethyl acetate together with azathioprine and the derivative was retained on the reversed-phase column better than 6-mercaptopurine. In addition, 6-mercaptopurine-N-ethylmaleimide absorbed at the same wavelength (280 nm) as azathioprine. Consequently, this derivatization procedure enabled the simultaneous extraction, separation, and detection of these compounds.

High-Sensitivity GaN Microchemical Sensors

NASA Technical Reports Server (NTRS)

Son, Kyung-ah; Yang, Baohua; Liao, Anna; Moon, Jeongsun; Prokopuk, Nicholas

2009-01-01

Systematic studies have been performed on the sensitivity of GaN HEMT (high electron mobility transistor) sensors using various gate electrode designs and operational parameters. The results here show that a higher sensitivity can be achieved with a larger W/L ratio (W = gate width, L = gate length) at a given D (D = source-drain distance), and multi-finger gate electrodes offer a higher sensitivity than a one-finger gate electrode. In terms of operating conditions, sensor sensitivity is strongly dependent on transconductance of the sensor. The highest sensitivity can be achieved at the gate voltage where the slope of the transconductance curve is the largest. This work provides critical information about how the gate electrode of a GaN HEMT, which has been identified as the most sensitive among GaN microsensors, needs to be designed, and what operation parameters should be used for high sensitivity detection.

BKV Agnoprotein Interacts with α-Soluble N-Ethylmaleimide-Sensitive Fusion Attachment Protein, and Negatively Influences Transport of VSVG-EGFP

PubMed Central

Johannessen, Mona; Walquist, Mari; Gerits, Nancy; Dragset, Marte; Spang, Anne; Moens, Ugo

2011-01-01

Background The human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive. Principal Findings As a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them α-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and α-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and α-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with α-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis. Conclusions We have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with α-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter. PMID:21931730

In vitro effects of platinum compounds on renal cellular respiration in mice.

PubMed

Almarzooqi, Saeeda-S; Alfazari, Ali-S; Abdul-Kader, Hidaya-M; Saraswathiamma, Dhanya; Albawardi, Alia-S; Souid, Abdul-Kader

2015-01-01

Cisplatin, carboplatin and oxaliplatin are structurally-related compounds, which are commonly used in cancer therapy. Cisplatin (Platinol(®)) has Boxed Warning stating: "Cumulative renal toxicity associated with PLATINOL is severe", while carboplatin and oxaliplatin are less nephrotoxic. These drugs form platinum adducts with cellular DNA. Their bindings to cellular thiols (e.g., glutathione and metallothionein) are known to contribute to drug resistance while thiol depletion augments platinum toxicity. Using phosphorescence oxygen analyzer, this study investigated the effects of platinum drugs on renal cellular respiration (mitochondrial O2 consumption) in the presence and absence of the thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion). Renal cellular ATP was also determined. Kidney fragments from C57BL/6 mice were incubated at 37 °C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2) with and without 100 μM platinum drug in the presence and absence of 100 μM N-ethylmaleimide for ≤ 6 h. Platinum drugs alone had no effects on cellular respiration (P ≥ 0.143) or ATP (P ≥ 0.161). N-ethylmaleimide lowered cellular respiration (P ≤ 0.114) and ATP (P = 0.008). The combination of platinum drug and N-ethylmaleimide significantly lowered both cellular respiration (P ≤ 0.006) and ATP (P ≤ 0.003). Incubations with N-ethylmaleimide alone were associated with moderate-to-severe tubular necrosis. Incubations with cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of tubular necrosis. Tubular derangements were more prominent in carboplatin+N-ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs. oxaliplatin alone. These results demonstrate the adverse events of thiol depletion on platinum-induced nephrotoxicities. The results suggest cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced nephrotoxicities.

SNARE-encoding genes VdSec22 and VdSso1 mediate protein secretion required for full virulence in Verticillium dahliae

USDA-ARS?s Scientific Manuscript database

Proteins that mediate cellular and subcellular membrane fusion are key factors in vesicular trafficking in all eukaryotic cells, including the secretion and transport of plant pathogen virulence factors. In this study, we identified vesicle fusion components that included 22 soluble N-ethylmaleimide...

[Tartrate-sensitive and tartrate-resistant acid phosphatases in Amoeba proteus].

PubMed

Sopina, V A; Beliaeva, T N

2000-01-01

In free-living Amoeba proteus (strain B), acid phosphatase (AcP) was examined by disc-electrophoresis in polyacrylamide gel. The tartrate-sensitive amebian AcP was greatly inhibited by dithiothreitol and Cu2+, and only partly inhibited by sodium orthovanadate, ammonium molybdate, EDTA, disodium salt and Mg2+, Ca2+, Zn2+ and Mn2+. On the contrary, it appeared to be resistant to sulfhydryl reagents--4(hydroxymercury) benzoic acid, sodium salt and N-ethylmaleimide. Unlike the tartrate-sensitive enzyme, the tartrate-resistant AcP was greatly inhibited by EDTA and partly inhibited by dithiothreitol, Mg2+ and Cu2+ (Mn2+ > Cu2+), being activated by orthovanadate, molybdate, sulfhydryl reagents, Mg2+, Ca2+ and Zn2+. Both tartrate-sensitive and tartrate-resistant AcPs lack apparently free SH-groups necessary for their catalytic activities. Using 2-naphthyl phosphate as a substrate at pH 4.5, six AcP electromorphs were revealed in cytosol and sediment, four of these being most frequently localized in the former, and two in the latter. Two other AcP electromorphs were confined to the sediment only. Depending on the quantity of sedimented amoebae making a homogenate (0.5 or 2.0 cm3), that was added to Percoll solution, the lysosomal AcP fraction in polyacrylamide gel was represented by one or two tartrate-sensitive electromorphs. Therefore, tartrate-resistant AcP in A. proteus may be a lysosomal enzyme, while tartrate-resistant AcP may correspond to serine/threonine protein phosphatase.

Design and synthesis study of the thermo-sensitive poly (N-vinylpyrrolidone-b- N, N-diethylacrylamide).

PubMed

Zhang, Xiayun; Yang, Zhongduo; Xie, Dengmin; Liu, Donglei; Chen, Zhenbin; Li, Ke; Li, Zhizhong; Tichnell, Brandon; Liu, Zhen

2018-01-01

The reversible addition fragmentation chain transfer (RAFT) polymerization method was adopted here to prepare a series of thermo-sensitive copolymers, poly (N,N-diethyl- acrylamide-b-N-vinylpyrrolidone). Their structures, molecular weight distribution and temperature sensitivity performances were characterized by the nuclear magnetic resonance ( 1 HNMR), the gel permeation chromatography (GPC) and the fluorescence spectrophotometer, respectively. It has been identified that the synthesis reaction of the block copolymer was living polymerization. The thermo-sensitivity study suggested that N-vinylpyrrolidone (NVP), played a key role on the lower critical solution temperature (LCST) performance.

Individual variability of human olfactory sensitivity to volatile steroids: Environmental and genetic factors.

PubMed

Voznessenskaya, V V; Klyuchnikova, M A

2017-03-01

The sensitivity to androstenone and possible factors, determining the sensitivity were investigated for the large sample of inhabitants of central Russia (n = 860). Specific anosmia was detected in 48.8% of subjects. Women were more sensitive to androstenone than men. The proportion of men, but not women perceiving the smell of androstenone as a strong one in the concentration used decreased with age. Smoking, blood group, or ethnicity had no significant effect on the expression of specific anosmia and the perception of androstenone odor intensity.

Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling*

PubMed Central

McGarvey, Jennifer C.; Xiao, Kunhong; Bowman, Shanna L.; Mamonova, Tatyana; Zhang, Qiangmin; Bisello, Alessandro; Sneddon, W. Bruce; Ardura, Juan A.; Jean-Alphonse, Frederic; Vilardaga, Jean-Pierre; Puthenveedu, Manojkumar A.; Friedman, Peter A.

2016-01-01

The G protein-coupled parathyroid hormone receptor (PTHR) regulates mineral-ion homeostasis and bone remodeling. Upon parathyroid hormone (PTH) stimulation, the PTHR internalizes into early endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes that promotes recycling of surface receptors. The C terminus of the PTHR contains a type I PDZ ligand that binds PDZ domain-containing proteins. Mass spectrometry identified sorting nexin 27 (SNX27) in isolated endosomes as a PTHR binding partner. PTH treatment enriched endosomal PTHR. SNX27 contains a PDZ domain and serves as a cargo selector for the retromer complex. VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes from cells stimulated with PTH. Molecular dynamics and protein binding studies establish that PTHR and SNX27 interactions depend on the PDZ recognition motif in PTHR and the PDZ domain of SNX27. Depletion of either SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling following agonist stimulation. Mutating the PDZ ligand of PTHR abolished the interaction with SNX27 but did not affect the overall rate of recycling, suggesting that PTHR may directly engage the retromer complex. Coimmunoprecipitation and overlay experiments show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially assemble a ternary complex with PTHR and SNX27. SNX27-independent recycling may involve N-ethylmaleimide-sensitive factor, which binds both PDZ intact and mutant PTHRs. We conclude that PTHR recycles rapidly through at least two pathways, one involving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide-sensitive factor. PMID:27008860

High Sensitive pH Sensor Based on AlInN/GaN Heterostructure Transistor.

PubMed

Dong, Yan; Son, Dong-Hyeok; Dai, Quan; Lee, Jun-Hyeok; Won, Chul-Ho; Kim, Jeong-Gil; Chen, Dunjun; Lee, Jung-Hee; Lu, Hai; Zhang, Rong; Zheng, Youdou

2018-04-24

The AlInN/GaN high-electron-mobility-transistor (HEMT) indicates better performances compared with the traditional AlGaN/GaN HEMTs. The present work investigated the pH sensor functionality of an analogous HEMT AlInN/GaN device with an open gate. It was shown that the Al 0.83 In 0.17 N/GaN device demonstrates excellent pH sense functionality in aqueous solutions, exhibiting higher sensitivity (−30.83 μA/pH for AlInN/GaN and −4.6 μA/pH for AlGaN/GaN) and a faster response time, lower degradation and good stability with respect to the AlGaN/GaN device, which is attributed to higher two-dimensional electron gas (2DEG) density and a thinner barrier layer in Al 0.83 In 0.17 N/GaN owning to lattice matching. On the other hand, the open gate geometry was found to affect the pH sensitivity obviously. Properly increasing the width and shortening the length of the open gate area could enhance the sensitivity. However, when the open gate width is too larger or too small, the pH sensitivity would be suppressed conversely. Designing an optimal ratio of the width to the length is important for achieving high sensitivity. This work suggests that the AlInN/GaN-based 2DEG carrier modulated devices would be good candidates for high-performance pH sensors and other related applications.

Alcohol induces synaptotagmin 1 expression in neurons via activation of heat shock factor 1.

PubMed

Varodayan, F P; Pignataro, L; Harrison, N L

2011-10-13

Many synapses within the central nervous system are sensitive to ethanol. Although alcohol is known to affect the probability of neurotransmitter release in specific brain regions, the effects of alcohol on the underlying synaptic vesicle fusion machinery have been little studied. To identify a potential pathway by which ethanol can regulate neurotransmitter release, we investigated the effects of acute alcohol exposure (1-24 h) on the expression of the gene encoding synaptotagmin 1 (Syt1), a synaptic protein that binds calcium to directly trigger vesicle fusion. Syt1 was identified in a microarray screen as a gene that may be sensitive to alcohol and heat shock. We found that Syt1 mRNA and protein expression are rapidly and robustly up-regulated by ethanol in mouse cortical neurons, and that the distribution of Syt1 protein along neuronal processes is also altered. Syt1 mRNA up-regulation is dependent on the activation of the transcription factor heat shock factor 1 (HSF1). The transfection of a constitutively active Hsf1 construct into neurons stimulates Syt1 transcription, while transfection of Hsf1 small interfering RNA (siRNA) or a constitutively inactive Hsf1 construct into neurons attenuates the induction of Syt1 by ethanol. This suggests that the activation of HSF1 can induce Syt1 expression and that this may be a mechanism by which alcohol regulates neurotransmitter release during brief exposures. Further analysis revealed that a subset of the genes encoding the core synaptic vesicle fusion (soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor; SNARE) proteins share this property of induction by ethanol, suggesting that alcohol may trigger a specific coordinated adaptation in synaptic function. This molecular mechanism could explain some of the changes in synaptic function that occur following alcohol administration and may be an important step in the process of neuronal adaptation to alcohol. Copyright © 2011 IBRO. Published by

N,N'-Bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine based d(10) transition metal complexes and their utilization in co-sensitized solar cells.

PubMed

Wei, Liguo; Yang, Yulin; Fan, Ruiqing; Na, Yong; Wang, Ping; Dong, Yuwei; Yang, Bin; Cao, Wenwu

2014-08-07

N,N'-Bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine based four-coordinated d(10) transition metal complexes (named ML, M = Zn, Cd, Hg) were synthesized and employed as co-sensitizers and co-adsorbents in combination with a ruthenium complex N719 in dye sensitized solar cells. After co-sensitization, not only the incident-photon-to-current conversion efficiency is enhanced but also the dark current is reduced. A short circuit current density of 14.46 mA cm(-2), an open circuit voltage of 0.74 V and a fill factor of 0.62 corresponding to an overall conversion efficiency of 6.65% under AM 1.5 G solar irradiation were achieved when ZnL was used as a co-sensitizer, which are much higher than that for DSSCs only sensitized by N719 (5.22%) under the same conditions. The improvement in efficiency is attributed to the fact that N,N'-bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine coordinated complexes overcome the deficiency of N719 absorption in the low wavelength region of the visible spectrum, prevent its aggregation, offset competitive visible light absorption of I3(-) and reduce charge recombination due to formation of an effective cover layer of the dye molecules on the TiO2 surface. As a result, the synthesized complexes are promising candidates as co-adsorbents and co-sensitizers for highly efficient DSSCs.

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors.

PubMed

Chen, Yan; Sun, Ji; Lu, Ying; Tao, Chun; Huang, Jingbin; Zhang, He; Yu, Yuan; Zou, Hao; Gao, Jing; Zhong, Yanqiang

2013-01-01

pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/-]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy.

The Colony-Stimulating Factor 3 Receptor T640N Mutation Is Oncogenic, Sensitive to JAK Inhibition, and Mimics T618I.

PubMed

Maxson, Julia E; Luty, Samuel B; MacManiman, Jason D; Paik, Jason C; Gotlib, Jason; Greenberg, Peter; Bahamadi, Swaleh; Savage, Samantha L; Abel, Melissa L; Eide, Christopher A; Loriaux, Marc M; Stevens, Emily A; Tyner, Jeffrey W

2016-02-01

Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in the majority of chronic neutrophilic leukemia (CNL) and a smaller percentage of atypical chronic myeloid leukemia (aCML) cases. Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. In this study, we assess the importance of the CSF3R T640N mutation as a marker of CNL/aCML and potential therapeutic target. Sanger sequencing of leukemia samples was performed to identify CSF3R mutations in CNL and aCML. The oncogenicity of the CSF3R T640N mutation relative to the T618I mutation was assessed by cytokine independent growth assays and by mouse bone marrow transplant. Receptor dimerization and O-glycosylation of the mutants was assessed by Western blot, and JAK inhibitor sensitivity was assessed by colony assay. Here, we identify a CSF3R T640N mutation in two patients with CNL/aCML, one of whom was originally diagnosed with MDS and acquired the T640N mutation upon evolution of disease to aCML. The T640N mutation is oncogenic in cellular transformation assays and an in vivo mouse bone marrow transplantation model. It exhibits many similar phenotypic features to T618I, including ligand independence and altered patterns of O-glycosylation--despite the transmembrane location of T640 preventing access by GalNAc transferase enzymes. Cells transformed by the T640N mutation are sensitive to JAK kinase inhibition to a similar degree as cells transformed by CSF3R T618I. Because of its similarities to CSF3R T618I, the T640N mutation likely has diagnostic and therapeutic relevance in CNL/aCML. ©2015 American Association for Cancer Research.

Enemy at the gates: traffic at the plant cell pathogen interface.

PubMed

Hoefle, Caroline; Hückelhoven, Ralph

2008-12-01

The plant apoplast constitutes a space for early recognition of potentially harmful non-self. Basal pathogen recognition operates via dynamic sensing of conserved microbial patterns by pattern recognition receptors or of elicitor-active molecules released from plant cell walls during infection. Recognition elicits defence reactions depending on cellular export via SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex-mediated vesicle fusion or plasma membrane transporter activity. Lipid rafts appear also involved in focusing immunity-associated proteins to the site of pathogen contact. Simultaneously, pathogen effectors target recognition, apoplastic host proteins and transport for cell wall-associated defence. This microreview highlights most recent reports on the arms race for plant disease and immunity at the cell surface.

Regulation of platelet granule exocytosis by S-nitrosylation

PubMed Central

Morrell, Craig N.; Matsushita, Kenji; Chiles, Kelly; Scharpf, Robert B.; Yamakuchi, Munekazu; Mason, Rebecca J. A.; Bergmeier, Wolfgang; Mankowski, Joseph L.; Baldwin, William M.; Faraday, Nauder; Lowenstein, Charles J.

2005-01-01

Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and α-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis. PMID:15738422

Surface sensitization mechanism on negative electron affinity p-GaN nanowires

NASA Astrophysics Data System (ADS)

Diao, Yu; Liu, Lei; Xia, Sihao; Feng, Shu; Lu, Feifei

2018-03-01

The surface sensitization is the key to prepare negative electron affinity photocathode. The thesis emphasizes on the study of surface sensitization mechanism of p-type doping GaN nanowires utilizing first principles based on density function theory. The adsorption energy, work function, dipole moment, geometry structure, electronic structure and optical properties of Mg-doped GaN nanowires surfaces with various coverages of Cs atoms are investigated. The GaN nanowire with Mg doped in core position is taken as the sensitization base. At the initial stage of sensitization, the best adsorption site for Cs atom on GaN nanowire surface is BN, the bridge site of two adjacent N atoms. Surface sensitization generates a p-type internal surface with an n-type surface state, introducing a band bending region which can help reduce surface barrier and work function. With increasing Cs coverage, work functions decrease monotonously and the "Cs-kill" phenomenon disappears. For Cs coverage of 0.75 ML and 1 ML, the corresponding sensitization systems reach negative electron affinity state. Through surface sensitization, the absorption curves are red shifted and the absorption coefficient is cut down. All theoretical calculations can guide the design of negative electron affinity Mg doped GaN nanowires photocathode.

Arrest of trans-SNARE zippering uncovers loosely and tightly docked intermediates in membrane fusion.

PubMed

Yavuz, Halenur; Kattan, Iman; Hernandez, Javier Matias; Hofnagel, Oliver; Witkowska, Agata; Raunser, Stefan; Walla, Peter Jomo; Jahn, Reinhard

2018-04-17

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins mediate intracellular membrane fusion in the secretory pathway. They contain conserved regions, termed SNARE motifs, that assemble between opposing membranes directionally from their N-termini to their membrane-proximal C-termini in a highly exergonic reaction. However, how this energy is utilized to overcome the energy barriers along the fusion pathway is still under debate. Here we have used mutants of the SNARE synaptobrevin to arrest trans-SNARE zippering at defined stages. We have uncovered two distinct vesicle docking intermediates, where the membranes are loosely and tightly connected, respectively. The tightly connected state is irreversible and independent of maintaining assembled SNARE complexes. Together, our results shed new light on the intermediate stages along the pathway of membrane fusion. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Photo-sensitization of ZnS nanoparticles with renowned ruthenium dyes N3, N719 and Z907 for application in solid state dye sensitized solar cells: A comparative study.

PubMed

Nosheen, Erum; Shah, Syed Mujtaba; Hussain, Hazrat; Murtaza, Ghulam

2016-09-01

This article presents a comprehensive relative report on the grafting of ZnS with renowned ruthenium ((Ru) dyes i.e. N3, N719 and Z907) and gives insight into their charge transfer interaction and sensitization mechanism for boosting solar cell efficiency. Influence of dye concentration on cell performance is also reported here. ZnS nanoparticles synthesized by a simple coprecipitation method with an average particle size of 15±2nm were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Elemental dispersive X-ray analysis (EDAX), tunneling electron microscopy (TEM) and UV-Visible (UV-Vis) spectroscopy. UV-Vis, photoluminescence (PL) and Fourier transform infra-red (FT-IR) spectroscopy confirms the successful grafting of these dyes over ZnS nanoparticles surface. Low-energy metal-to-ligand charge-transfer transition (MLCT) bands of dyes are mainly affected on grafting over the nanoparticle surface. Moreover their current voltage (I-V) results confirm the efficiency enhancement in ZnS solid state dye sensitized solar cells (SSDSSCs) owing to effective sensitization of this material with Ru dyes and helps in finding the optimum dye concentration for nanoparticles sensitization. Highest rise in overall solar cell efficiency i.e. 64% of the reference device has been observed for 0.3mM N719-ZnS sample owing to increased open circuit voltage (Voc) and fill factor (FF). Experimental and proposed results were found in good agreement with each other. Copyright © 2016 Elsevier B.V. All rights reserved.

N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations.

PubMed

Morais-Silva, Gessynger; Alves, Gabrielle Cunha; Marin, Marcelo T

2016-11-01

Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is ΔFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction. Recent works have shown a role for the imbalance of glutamatergic neurotransmission in the symptoms found in addicted people. In this sense, the treatment with N-acetylcysteine, a l-cysteine prodrug that acts by restoring extrasynaptic concentrations of glutamate through the activation of cystine-glutamate antiporter, has shown promising results in the treatment of addiction. Thus, an animal model of behavioural sensitization was used to evaluate the effects of N-acetylcysteine treatment in the behavioural and molecular alterations induced by chronic ethanol administration. Swiss mice were subject to 13 days of daily ethanol administration to induce behavioural sensitization. Two hours before each ethanol administration and locomotor activity evaluation, the animals received intraperitoneally N-acetylcysteine injections. Immediately after the last test session, their brains were removed for ΔFosB and cystine-glutamate antiporter quantification. It was found that N-acetylcysteine treatment blocked ethanol-induced behavioural sensitization, the increase of ΔFosB content in the prefrontal cortex, and its reduction in the nucleus accumbens. The results suggest a possible use of N-acetylcysteine in ethanol-related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metal Oxide Gas Sensors: Sensitivity and Influencing Factors

PubMed Central

Wang, Chengxiang; Yin, Longwei; Zhang, Luyuan; Xiang, Dong; Gao, Rui

2010-01-01

Conductometric semiconducting metal oxide gas sensors have been widely used and investigated in the detection of gases. Investigations have indicated that the gas sensing process is strongly related to surface reactions, so one of the important parameters of gas sensors, the sensitivity of the metal oxide based materials, will change with the factors influencing the surface reactions, such as chemical components, surface-modification and microstructures of sensing layers, temperature and humidity. In this brief review, attention will be focused on changes of sensitivity of conductometric semiconducting metal oxide gas sensors due to the five factors mentioned above. PMID:22294916

Sixteen-Item Anxiety Sensitivity Index: Confirmatory Factor Analytic Evidence, Internal Consistency, and Construct Validity in a Young Adult Sample from the Netherlands

ERIC Educational Resources Information Center

Vujanovic, Anka A.; Arrindell, Willem A.; Bernstein, Amit; Norton, Peter J.; Zvolensky, Michael J.

2007-01-01

The present investigation examined the factor structure, internal consistency, and construct validity of the 16-item Anxiety Sensitivity Index (ASI; Reiss Peterson, Gursky, & McNally 1986) in a young adult sample (n = 420) from the Netherlands. Confirmatory factor analysis was used to comparatively evaluate two-factor, three-factor, and…

Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis.

PubMed

Ma, Lu; Rebane, Aleksander A; Yang, Guangcan; Xi, Zhiqun; Kang, Yuhao; Gao, Ying; Zhang, Yongli

2015-12-23

Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD, and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

Is the Paracoccus halodenitrificans ATPase a chimeric enzyme?

NASA Technical Reports Server (NTRS)

Hochstein, L. I.

1996-01-01

Membranes from Paracoccus halodenitrificans contain an ATPase that is most active in the absence of NaCl. The most unusual characteristic of the enzyme is its pattern of sensitivity to various inhibitors. Azide and rhodamine 6G, inhibitors of F1F0-ATPases, inhibit ATP hydrolysis as do bafilomycin A1, concanamycin A (folimycin), N-ethylmaleimide, and p-chloromercuriphenylsulfonate which are inhibitors of vacuolar ATPases. This indiscriminate sensitivity suggests that this ATPase may be a hybrid and that caution should be exercised when using inhibition as a diagnostic for distinguishing between F1F0-ATPases and vacuolar ATPases.

Progress in understanding the neuronal SNARE function and its regulation.

PubMed

Yoon, T-Y; Shin, Y-K

2009-02-01

Vesicle budding and fusion underlies many essential biochemical deliveries in eukaryotic cells, and its core fusion machinery is thought to be built on one protein family named soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE). Recent technical advances based on site-directed fluorescence labelling and nano-scale detection down to the single-molecule level rapidly unveiled the protein and the lipid intermediates along the fusion pathway as well as the molecular actions of fusion effectors. Here we summarize these new exciting findings in context with a new mechanistic model that reconciles two existing fusion models: the proteinaceous pore model and the hemifusion model. Further, we attempt to locate the points of action for the fusion effectors along the fusion pathway and to delineate the energetic interplay between the SNARE complexes and the fusion effectors.

Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.

PubMed

Knowles, Joshua W; Xie, Weijia; Zhang, Zhongyang; Chennamsetty, Indumathi; Chennemsetty, Indumathi; Assimes, Themistocles L; Paananen, Jussi; Hansson, Ola; Pankow, James; Goodarzi, Mark O; Carcamo-Orive, Ivan; Morris, Andrew P; Chen, Yii-Der I; Mäkinen, Ville-Petteri; Ganna, Andrea; Mahajan, Anubha; Guo, Xiuqing; Abbasi, Fahim; Greenawalt, Danielle M; Lum, Pek; Molony, Cliona; Lind, Lars; Lindgren, Cecilia; Raffel, Leslie J; Tsao, Philip S; Schadt, Eric E; Rotter, Jerome I; Sinaiko, Alan; Reaven, Gerald; Yang, Xia; Hsiung, Chao A; Groop, Leif; Cordell, Heather J; Laakso, Markku; Hao, Ke; Ingelsson, Erik; Frayling, Timothy M; Weedon, Michael N; Walker, Mark; Quertermous, Thomas

2015-04-01

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

Enhanced pH sensitivity of AlGaN/GaN ion-sensitive field effect transistor with Al2O3 synthesized by atomic layer deposition

NASA Astrophysics Data System (ADS)

Wang, Lei; Li, Liuan; Zhang, Tong; Liu, Xinke; Ao, Jin-Ping

2018-01-01

In this study, we evaluated the pH sensitivity enhancement of AlGaN/GaN ion-sensitive field-effect transistor (ISFET) coated by Al2O3 film on the sensing area utilizing atomic layer deposition (ALD). The presence of the Al2O3 film leads to an obvious reduction of surface state density as well as leakage current in the solution, which is beneficial for improving the stability of the ISFET. Furthermore, the sensitivity of the ISFET was improved to 57.8 mV/pH, which is very close to the Nernstian limit at room temperature. The pH sensitivity enhancement can be explained by the higher density of sensing site as well as better surface hydrophilicity.

Sensitivity factor of the axial-symmetric transmission gauge: Deviation and long-term variation

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

Takahashi, N.; Tuzi, Y.; Arakawa, I.

2007-07-15

The deviation of the sensitivity factors for about 50 sensors of the axial-symmetric transmission gauge (ATG) was examined. The deviation has been compared with that for about 30 sensors of the B-A gauge and for about 30 sensors of the extractor gauge. Almost the same deviations are found for the above three types of gauges. The long-term variations of the sensitivity factors for two sensors of the ATG were also measured during four years. After the initial change with operating time, the sensitivity factor stabilized after long-term operation. The room temperature effect of the sensitivity factor plays an important rolemore » on the total pressure measurement by an ionization gauge, but the change of the sensitivity factor was larger than the room temperature effect. The reason for the change of the factor is estimated in connection with the annealing and the alignment of the filament and with the deviation of the place of electron emission on the filament.« less

Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses.

PubMed

Sakai-Tagawa, Yuko; Ozawa, Makoto; Tamura, Daisuke; Le, Mai thi Quynh; Nidom, Chairul A; Sugaya, Norio; Kawaoka, Yoshihiro

2010-08-01

Simple and rapid diagnosis of influenza is useful for making treatment decisions in the clinical setting. Although many influenza rapid diagnostic tests (IRDTs) are available for the detection of seasonal influenza virus infections, their sensitivity for other viruses, such as H5N1 viruses and the recently emerged swine origin pandemic (H1N1) 2009 virus, remains largely unknown. Here, we examined the sensitivity of 20 IRDTs to various influenza virus strains, including H5N1 and 2009 pandemic H1N1 viruses. Our results indicate that the detection sensitivity to swine origin H1N1 viruses varies widely among IRDTs, with some tests lacking sufficient sensitivity to detect the early stages of infection when the virus load is low.

The Relationship of Workplace Culture With Nursing-Sensitive Organizational Factors.

PubMed

Hahtela, Nina; McCormack, Brendan; Paavilainen, Eija; Slater, Paul; Helminen, Mika; Suominen, Tarja

2015-01-01

The aim of this study is to explore the relations of workplace culture on nursing-sensitive organizational factors. The need for standardized and valid measures for nursing-sensitive organizational outcomes has already been recognized in the literature. A cross-sectional questionnaire survey of 21 inpatient acute care units in 9 organizations at the municipal primary healthcare level was conducted. Participants included licensed practical nurses, registered nurses, and nurse managers. Workplace culture, especially the overarching factor of stress, correlated with the use of supplemental nursing staff and patients' length of stay. It is essential to find and test workplace-sensitive indicators so that managers will have a wider range of methods to plan and evaluate nursing outcomes.

HgNO3 sensitivity of AlGaN/GaN field effect transistors functionalized with phytochelating peptides

NASA Astrophysics Data System (ADS)

Rohrbaugh, Nathaniel; Hernandez-Balderrama, Luis; Kaess, Felix; Kirste, Ronny; Collazo, Ramon; Ivanisevic, Albena

2016-06-01

This study examined the conductance sensitivity of AlGaN/GaN field effect transistors in response to varying Hg/HNO3 solutions. FET surfaces were covalently functionalized with phytochelatin-5 peptides in order to detect Hg in solution. Results showed a resilience of peptide-AlGaN/GaN bonds in the presence of strong HNO3 aliquots, with significant degradation in FET ID signal. However, devices showed strong and varied response to Hg concentrations of 1, 10, 100, and 1000 ppm. The gathered statistically significant results indicate that peptide terminated AlGaN/GaN devices are capable of differentiating between Hg solutions and demonstrate device sensitivity.

S-nitrosylation and S-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca2+ sensitivity in rat fast-twitch muscle fibers.

PubMed

Dutka, T L; Mollica, J P; Lamboley, C R; Weerakkody, V C; Greening, D W; Posterino, G S; Murphy, R M; Lamb, G D

2017-03-01

Nitric oxide is generated in skeletal muscle with activity and decreases Ca 2+ sensitivity of the contractile apparatus, putatively by S- nitrosylation of an unidentified protein. We investigated the mechanistic basis of this effect and its relationship to the oxidation-induced increase in Ca 2+ sensitivity in mammalian fast-twitch (FT) fibers mediated by S- glutathionylation of Cys134 on fast troponin I (TnI f ). Force-[Ca 2+ ] characteristics of the contractile apparatus in mechanically skinned fibers were assessed by direct activation with heavily Ca 2+ -buffered solutions. Treatment with S- nitrosylating agents, S- nitrosoglutathione (GSNO) or S- nitroso- N -acetyl-penicillamine (SNAP), decreased pCa 50 ( = -log 10 [Ca 2+ ] at half-maximal activation) by ~-0.07 pCa units in rat and human FT fibers without affecting maximum force, but had no effect on rat and human slow-twitch fibers or toad or chicken FT fibers, which all lack Cys134. The Ca 2+ sensitivity decrease was 1 ) fully reversed with dithiothreitol or reduced glutathione, 2 ) at least partially reversed with ascorbate, indicative of involvement of S-nitrosylation, and 3 ) irreversibly blocked by low concentration of the alkylating agent, N -ethylmaleimide (NEM). The biotin-switch assay showed that both GSNO and SNAP treatments caused S- nitrosylation of TnI f S- glutathionylation pretreatment blocked the effects of S- nitrosylation on Ca 2+ sensitivity, and vice-versa. S- nitrosylation pretreatment prevented NEM from irreversibly blocking S- glutathionylation of TnI f and its effects on Ca 2+ sensitivity, and likewise S- glutathionylation pretreatment prevented NEM block of S- nitrosylation. Following substitution of TnI f into rat slow-twitch fibers, S- nitrosylation treatment caused decreased Ca 2+ sensitivity. These findings demonstrate that S- nitrosylation and S- glutathionylation exert opposing effects on Ca 2+ sensitivity in mammalian FT muscle fibers, mediated by competitive actions on Cys134

Food acceptance and anthropometry in relation to 6-n-propylthiouracil sensitivity in Japanese college women.

PubMed

Nagai, Ayako; Kubota, Masaru; Morinaga, Kanako; Higashiyama, Yukie

2017-01-01

Differences in anthropometry and food acceptance among tasters and non-tasters of 6-n-propylthiouracil has been well studied in Western countries. However, reports on this issue from Asian countries are still limited. Healthy Japanese students attending Nara Women's University (n=153) were recruited and classified into 3 groups based on taste sensitivity to a 0.32 mM 6-npropylthiouracil solution as scored on a labeled magnitude scale. Accordingly, the study population consisted of 34 non-tasters, 78 medium-tasters, and 41 super-tasters. Self-reported food intake was assessed using a food frequency questionnaire. Self-reported food preferences were established using a food checklist listing 63 food items. Although subjects in the 6-n-propylthiouracil non-taster group showed a significantly higher body height and weight than subjects in the taster groups, body mass index was comparable among three groups. Intakes of calories, 3 macronutrients, β-carotene and vitamin C did not differ significantly between groups, but the intake of green and yellow vegetables was significantly lower in the taster groups. Among the 5 factors defined by a factor analysis performed with 277 age- and BMI-matched Japanese female students, the taster groups showed a significantly reduced preference for green and cruciferous vegetables alone. To the best of our knowledge, this is the first comprehensive report investigating associations between anthropometry, food intake, and food preference in relation to 6-n-propylthiouracil sensitivity in Asian countries. The effect of this tendency towards an aversion to vegetables including cruciferous ones among females on living a healthy life remains to be investigated.

Hyperpolarized 15N-pyridine Derivatives as pH-Sensitive MRI Agents

PubMed Central

Jiang, Weina; Lumata, Lloyd; Chen, Wei; Zhang, Shanrong; Kovacs, Zoltan; Sherry, A. Dean; Khemtong, Chalermchai

2015-01-01

Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an investigation of hyperpolarized 15N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their 15N chemical shifts were found to be highly sensitive to pH. These probes displayed sharp 15N resonances and large differences in chemical shifts (Δδ >90 ppm) between their free base and protonated forms. These favorable features make these agents highly suitable candidates for the detection of small changes in tissue pH near physiological values. PMID:25774436

Sulphate transport by H+ symport and by the dicarboxylate carrier in mitochondria.

PubMed Central

Saris, N E

1980-01-01

1. Swelling of mitochondria was induced in non-respiring mitochondria by 30 mM or more Na2SO4 or by respiration in the presence of K2SO4. Respiration-drive swelling resulted in loss of respiratory control. Sulphate, when present at 10 mM concentration, promoted the release of accumulated Ca2+. 2. Swelling was prevented by N-ethylmaleimide and formaldehyde, known inhibitors of the phosphate carrier. Sulphate-induced swelling was more sensitive to the inhibitors than was phosphate-induced swelling. At lower concentration of sulphate, 5 mM, an alkalinisation of the medium was observed in addition of sulphate, indicating H+-sulphate symport. There was competition between sulphate and phosphate for transport by this mechanism. It is suggested that sulphate may be transported, though at a comparatively slow rate, by the phosphate carrier. 3. Uptake of sulphate was stimulated when preceded by energy-dependent accumulation of Ba2+, especially when acetate was also present, indicating precipitation of BaSO4 in the matrix. Using this system the influx of sulphate was studied at lower concentrations, 10 mM or less. the contributions of the H+ symporter (sensitive to N-ethylmaleimide) and the dicarboxylate carrier (sensitive to butylmalonate) could then be studied. The dicarboxylate carrier had a lower Km and was mainly responsible for sulphate transport at lower concentration range. At 10 mM-sulphate the transport rates by the two systems appeared to be similar; at still higher concentrations the H+ symporter may become more important. PMID:7236245

The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1.

PubMed

Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

2016-12-02

Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychosocial Factors and Central Sensitivity Syndromes

PubMed Central

Adams, Leah M.; Turk, Dennis C.

2016-01-01

Central sensitivity syndromes (CSSs) represent a heterogeneous group of disorders (e.g., fibromyalgia [FM], irritable bowel syndrome [IBS], chronic headache, temporomandibular disorders [TMDs], pelvic pain syndromes) that share common symptoms, with persistent pain being the most prominent feature. Although the etiology and pathophysiology of CSSs are currently incompletely understood, central sensitization has emerged as one of the significant mechanisms. Given that there are currently no known cures for CSSs, people living with these disorders must learn to cope with and manage their symptoms throughout their lives. Medical interventions alone have not proven to be sufficient for helping people with CSSs manage their symptoms. A biopsychosocial perspective that considers the ways that biological, psychological, and social factors work independently and jointly to affect a person's experience is the most effective conceptualization and guide for effective treatment. In this article, we discuss several psychological and social features that may influence the experience of a person with CSS and their symptom management, regardless of their specific diagnosis. We highlight the longitudinal aspect of adjustment to illness, the distinction between psychosocial factors as causes of symptoms versus modifiers and perpetuators of symptoms, dispel the notion that all patients with the same diagnosis are a homogeneous group (the “patient-uniformity myth”), and acknowledge the importance of environmental and situational context on symptom management for individuals with any CSS. PMID:26088211

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

PubMed Central

Chen, Yan; Sun, Ji; Lu, Ying; Tao, Chun; Huang, Jingbin; Zhang, He; Yu, Yuan; Zou, Hao; Gao, Jing; Zhong, Yanqiang

2013-01-01

pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/−]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy. PMID:23637529

Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy.

PubMed

Frick, Marcel; Fischer, Jörg; Helbling, Arthur; Ruëff, Franziska; Wieczorek, Dorothea; Ollert, Markus; Pfützner, Wolfgang; Müller, Sabine; Huss-Marp, Johannes; Dorn, Britta; Biedermann, Tilo; Lidholm, Jonas; Ruecker, Gerta; Bantleon, Frank; Miehe, Michaela; Spillner, Edzard; Jakob, Thilo

2016-12-01

Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which have been reported to be underrepresented in therapeutic HBV preparations. We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome. HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge. No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG 4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable. Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Sensory Processing Sensitivity: Factors of the Highly Sensitive Person Scale and Their relationships to Personality and Subjective Health Complaints.

PubMed

Listou Grimen, Hanne; Diseth, Åge

2016-12-01

The aim of the present study was to examine the factor structure of a Norwegian version of the Highly Sensitive Person Scale (HSPS) and to investigate how sensory processing sensitivity (SPS) is related to personality traits of neuroticism, extraversion, and openness and to subjective health complaints (SHC) in a sample of 167 undergraduate psychology students. The results showed that the variance in a shortened version of the HSPS was best described by three separate factors: ease of excitation (EOE), aesthetic sensitivity (AES), and low sensory threshold (LST). Furthermore, the result showed than an overall SPS factor (EOE, LST, and AES combined) was predicted positively by neuroticism and openness and negatively by extraversion. With respect to SHC, the results showed that EOE and LST were positively associated with psychological health complaints. However, the personality trait of neuroticism contributed more than the SPS factors as predictor of SHC. In conclusion, the present study supported a shortened version of the HSPS and its relation to personality factors and SHC. © The Author(s) 2016.

Molecular switch-modulated fluorescent copper nanoclusters for selective and sensitive detection of histidine and cysteine.

PubMed

Gu, Zefeng; Cao, Zhijuan

2018-06-07

A novel assay for histidine and cysteine has been constructed based on modulation of fluorescent copper nanoclusters (CuNCs) by molecular switches. In our previous work, a dumbbell DNA template with a poly-T (thymine) loop has been developed as an excellent template for the formation of strongly fluorescent CuNCs. Herein, for the first time, we established this biosensor for sensing two amino acids by using dumbbell DNA-templated CuNCs as the single probe. Among 20 natural amino acids, only histidine and cysteine can selectively quench fluorescence emission of CuNCs, because of the specific interaction of these compounds with copper ions. Furthermore, by using nickel ions (Ni 2+ ) and N-ethylmaleimide as the masking agents for histidine and cysteine respectively, an integrated logic gate system was designed by coupling with the fluorescent CuNCs and demonstrated selective and sensitive detection of cysteine and histidine. Under optimal conditions, cysteine can be detected in the concentration ranges of 0.01-10.0 μM with the detection limit (DL) of as low as 98 pM, while histidine can be detected in the ranges of 0.05-40.0 μM with DL of 1.6 nM. In addition, histidine and cysteine can be observed with the naked eye under a hand-held UV lamp (DL, 50 nM), which can be easily adapted to automated high-throughput screening. Finally, the strategy has been successfully utilized for biological fluids. The proposed system can be conducted in homogeneous solution, eliminating the need for organic cosolvents, separation processes of nanomaterials, or any chemical modifications. Overall, the assay provides an alternative method for simultaneous detection of cysteine and histidine by taking the advantages of high speed, no label and enzyme requirement, and good sensitivity and specificity, and will satisfy the great demand for determination of amino acids in fields such as food processing, biochemistry, pharmaceuticals, and clinical analysis. Graphical abstract.

Risk factors associated with sensitization to hydroxyisohexyl 3-cyclohexene carboxaldehyde.

PubMed

Uter, Wolfgang; Geier, Johannes; Schnuch, Axel; Gefeller, Olaf

2013-08-01

Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) is a synthetic fragrance chemical and an important contact allergen, at least in Europe. Despite this importance, little is known about risk factors associated with this allergen. To examine factors from the history and clinical presentation of patch tested patients associated with HICC sensitization. Contact allergy surveillance data of 95 637 patients collected by the Information Network of Departments of Dermatology (IVDK, www.ivkd.org) in 2002-2011 were analysed. Point and interval estimates of the relative risk were derived from multifactorial logistic regression modelling. The overall prevalence of HICC sensitization was 2.24%. The strongest risk factors were polysensitization and dermatitis of the axillae, followed by dermatitis at other sites. No consistent and significant time trend was observed in this analysis. As compared with the youngest patients, the odds of HICC sensitization increased approximately three-fold in the 52-67-year age group, and strongly declined with further increasing age. The risk pattern with regard to age and affected anatomical site differed from that observed with other fragrance screening allergens. Cosmetic exposure, as broadly defined here, was a stronger and more prevalent individual risk factor than occupational exposure. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1

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

Kulebyakin, Konstantin; Penkov, Dmitry; IFOM – the FIRC Institute of Molecular Oncology, Via Adamello 16, Milan, 20139

Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to searchmore » new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. - Highlights: • A novel model of liver-specific Prep1 knockout is established. • Ablation of Prep1 in hepatocytes increases insulin sensitivity. • Prep1 controls hepatic insulin sensitivity by regulating localization of FOXO1. • Prep1 regulates

Hybrid organic/inorganic position-sensitive detectors based on PEDOT:PSS/n-Si

NASA Astrophysics Data System (ADS)

Javadi, Mohammad; Gholami, Mahdiyeh; Torbatiyan, Hadis; Abdi, Yaser

2018-03-01

Various configurations like p-n junctions, metal-semiconductor Schottky barriers, and metal-oxide-semiconductor structures have been widely used in position-sensitive detectors. In this report, we propose a PEDOT:PSS/n-Si heterojunction as a hybrid organic/inorganic configuration for position-sensitive detectors. The influence of the thickness of the PEDOT:PSS layer, the wavelength of incident light, and the intensity of illumination on the device performance are investigated. The hybrid PSD exhibits very high sensitivity (>100 mV/mm), excellent nonlinearity (<3%), and a response correlation coefficient (>0.995) with a response time of <4 ms to the inhomogeneous IR illumination. The presented hybrid configuration also benefits from a straightforward low-temperature fabrication process. These advantages of the PEDOT:PSS/n-Si heterojunction are very promising for developing a new class of position-sensitive detectors based on the hybrid organic/inorganic junctions.

Nursing students' understanding of factors influencing ethical sensitivity: A qualitative study.

PubMed

Borhani, Fariba; Abbaszadeh, Abbas; Mohsenpour, Mohaddeseh

2013-07-01

Ethical sensitivity is considered as a component of professional competency of nurses. Its effects on improvement of nurses' ethical performance and the therapeutic relationship between nurses and patients have been reported. However, very limited studies have evaluated ethical sensitivity. Since no previous Iranian research has been conducted in this regard, the present study aimed to review nursing students' understanding of effective factors on ethical sensitivity. This qualitative study was performed in Kerman, Iran, during 2009. It used semi-structured individual interviews with eight MSc nursing students to assess their viewpoints. It also included two focus groups. Purposive sampling was continued until data saturation. Data were analyzed using manifest content analysis. The students' understanding of factors influencing ethical sensitivity were summarized in five main themes including individual and spiritual characteristics, education, mutual understanding, internal and external controls, and experience of an immoral act. The findings of this study create a unique framework for sensitization of nurses in professional performance. The application of these factors in human resource management is reinforcement of positive aspects and decrease in negative aspects, in education can use for educational objectives setting, and in research can designing studies based on this framework and making related tools. It is noteworthy that presented classification was influenced by students themselves and mentioned to a kind of learning activity by them.

Binding of SEC11 Indicates Its Role in SNARE Recycling after Vesicle Fusion and Identifies Two Pathways for Vesicular Traffic to the Plasma Membrane[OPEN

PubMed Central

Karnik, Rucha; Zhang, Ben; Waghmare, Sakharam; Aderhold, Christin; Grefen, Christopher; Blatt, Michael R.

2015-01-01

SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins drive vesicle fusion in all eukaryotes and contribute to homeostasis, pathogen defense, cell expansion, and growth in plants. Two homologous SNAREs, SYP121 (=SYR1/PEN1) and SYP122, dominate secretory traffic to the Arabidopsis thaliana plasma membrane. Although these proteins overlap functionally, differences between SYP121 and SYP122 have surfaced, suggesting that they mark two discrete pathways for vesicular traffic. The SNAREs share primary cognate partners, which has made separating their respective control mechanisms difficult. Here, we show that the regulatory protein SEC11 (=KEULE) binds selectively with SYP121 to affect secretory traffic mediated by this SNARE. SEC11 rescued traffic block by dominant-negative (inhibitory) fragments of both SNAREs, but only in plants expressing the native SYP121. Traffic and its rescue were sensitive to mutations affecting SEC11 interaction with the N terminus of SYP121. Furthermore, the domain of SEC11 that bound the SYP121 N terminus was itself able to block secretory traffic in the wild type and syp122 but not in syp121 mutant Arabidopsis. Thus, SEC11 binds and selectively regulates secretory traffic mediated by SYP121 and is important for recycling of the SNARE and its cognate partners. PMID:25747882

Determination of Acceptor Concentration, Depletion Width, Donor Level Movement and Sensitivity Factor of ZnO on Diamond Heterojunction under UV Illumination

PubMed Central

Saw, Kim Guan; Tneh, Sau Siong; Yam, Fong Kwong; Ng, Sha Shiong; Hassan, Zainuriah

2014-01-01

The concentration of acceptor carriers, depletion width, magnitude of donor level movement as well as the sensitivity factor are determined from the UV response of a heterojunction consisting of ZnO on type IIb diamond. From the comparison of the I-V measurements in dark condition and under UV illumination we show that the acceptor concentration (∼1017 cm−3) can be estimated from p-n junction properties. The depletion width of the heterojunction is calculated and is shown to extend farther into the ZnO region in dark condition. Under UV illumination, the depletion width shrinks but penetrates both materials equally. The ultraviolet illumination causes the donor level to move closer to the conduction band by about 50 meV suggesting that band bending is reduced to allow more electrons to flow from the intrinsically n-type ZnO. The sensitivity factor of the device calculated from the change of threshold voltages, the ratio of dark and photocurrents and identity factor is consistent with experimental data. PMID:24586707

Purification and Properties of an ATPase from Sulfolobus solfataricus

NASA Technical Reports Server (NTRS)

Hochstein, Lawrence I.; Stan-Lotter, Helga

1992-01-01

A sulfite-activated ATPase isolated from Sulfolobus solfataricus had a relative molecular mass of 370,000. It was composed of three subunits whose relative molecular masses were 63,000, 48,000, and 24,000. The enzyme was inhibited by the vacuolar ATPase inhibitors nitrate and N-ethylmaleimide; 4-chloro-7-nitrobenzo-furazan (NBD-Cl) was also inhibitory. N-Ethylmaleimide was predominately bound to the largest subunit while NBD-CL was bound to both subunits. ATPase activity was inhibited by low concentrations of p-chloromercuri-phenyl sulfonate and the inhibition was reversed by cysteine which suggested that thiol groups were essential for activity. While the ATPase from S. solfataricus shared several properties with the ATPase from S. acidocaldarius there were significant differences. The latter enzyme was activated by sulfate and chloride and was unaffected by N-ethylmaleimide, whereas the S. solfataricus ATPase was inhibited by these anions as well as N-ethyimaleimide. These differences as well as differences that occur in other vacuolar-like ATPases isolated from the methanogenic and the extremely halophilic bacteria suggest the existence of several types of archaeal ATPases, none of which have been demonstrated to synthesize ATP.

Re-evaluation of the H+/site ratio of mitochondrial electron transport with the oxygen pulse technique.

PubMed

Brand, M D; Reynafarje, B; Lehninger, A L

1976-09-25

The number of protons ejected per pair of electrons passing each energy-conserving site in the electron transport chain (the H+/site ratio) has been investigated in rat liver mitochondria by means of the oxygen pulse technique introduced by Mitchell and Moyle (1967) (Biochem. J. 105, 1147-1162). The usual H+/site values of 2.0 observed by this method were found to be substantially underestimated as a result of the influx of phosphate into the mitochondria. This was shown by three different kinds of experiments. 1. Addition of N-ethylmaleimide or mersalyl, inhibitors of mitochondrial phosphate transport, increased the H+/site ratio from 2.0 to 3.0. The dependence of this effect on the concentration of either inhibitor was identical with that for inhibition of phosphate transport. Added phosphate diminished the H+/site ratio to values below 2.0 in the absence of N-ethylmaleimide. N-Ethylmaleimide protected the elevated H+/site ratio of 3.0 against the deleterious effect of added phosphate, but did not prevent a lowering effect of weak acid anions such as 3-hydroxybutyrate. 2. Prior washing of mitochondria to remove the endogenous phosphate that leaks out during the anaerobic preincubation led to H+/site ratios near 3.0, which were not increased by N-ethylmaleimide. Addition of low concentrations of phosphate to such phosphate-depleted mitochondria decreased the H+/site ratio to 2.0; addition of N-ethylmaleimide returned the ratio to 3.0. 3. Lowering the temperature to 5 degrees, which slows down phosphate transport, led to H+/site values of 3.0 even in the absence of N-ethylmaleimide. The H+/site ratio of 3.0 observed in the absence of phosphate movements was not dependent on any narrowly limited set of experimental conditions. It occurred with either Ca2+ or K+ (in the presence of valinomycin) as mobile permeant cation. It was independent of the concentration of succinate, oxygen, mitochondria, or rotenone, additions of Ca2+, Li+, or Na+ and was independent of

Dopamine D1A directly interacts with otoferlin synaptic pathway proteins: Ca2+ and phosphorylation underlie an NSF-to-AP2mu1 molecular switch.

PubMed

Selvakumar, Dakshnamurthy; Drescher, Marian J; Deckard, Nathan A; Ramakrishnan, Neeliyath A; Morley, Barbara J; Drescher, Dennis G

2017-01-01

Dopamine receptors regulate exocytosis via protein-protein interactions (PPIs) as well as via adenylyl cyclase transduction pathways. Evidence has been obtained for PPIs in inner ear hair cells coupling D1A to soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-related proteins snapin, otoferlin, N-ethylmaleimide-sensitive factor (NSF), and adaptor-related protein complex 2, mu 1 (AP2mu1), dependent on [Ca 2+ ] and phosphorylation. Specifically, the carboxy terminus of dopamine D1A was found to directly bind t-SNARE-associated protein snapin in teleost and mammalian hair cell models by yeast two-hybrid (Y2H) and pull-down assays, and snapin directly interacts with hair cell calcium-sensor otoferlin. Surface plasmon resonance (SPR) analysis, competitive pull-downs, and co-immunoprecipitation indicated that these interactions were promoted by Ca 2+ and occur together. D1A was also found to separately interact with NSF, but with an inverse dependence on Ca 2+ Evidence was obtained, for the first time, that otoferlin domains C2A, C2B, C2D, and C2F interact with NSF and AP2mu1, whereas C2C or C2E do not bind to either protein, representing binding characteristics consistent with respective inclusion or omission in individual C2 domains of the tyrosine motif YXXΦ. In competitive pull-down assays, as predicted by K D values from SPR (+Ca 2+ ), C2F pulled down primarily NSF as opposed to AP2mu1. Phosphorylation of AP2mu1 gave rise to a reversal: an increase in binding by C2F to phosphorylated AP2mu1 was accompanied by a decrease in binding to NSF, consistent with a molecular switch for otoferlin from membrane fusion (NSF) to endocytosis (AP2mu1). An increase in phosphorylated AP2mu1 at the base of the cochlear inner hair cell was the observed response elicited by a dopamine D1A agonist, as predicted. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

FACTORS AFFECTING SENSITIVITY OF CHEMICAL AND ECOLOGICAL RESPONSES OF MARINE EMBAYMEMTS TO NITROGEN LOADING

EPA Science Inventory

This paper summarizes an ongoing examination of the primary factors that affect sensitivity of marine embayment responses to nitrogen loading. Included is a discussion of two methods for using these factors: classification of embayments into discrete sensitivity classes and norma...

Uncertainty of relative sensitivity factors in glow discharge mass spectrometry

NASA Astrophysics Data System (ADS)

Meija, Juris; Methven, Brad; Sturgeon, Ralph E.

2017-10-01

The concept of the relative sensitivity factors required for the correction of the measured ion beam ratios in pin-cell glow discharge mass spectrometry is examined in detail. We propose a data-driven model for predicting the relative response factors, which relies on a non-linear least squares adjustment and analyte/matrix interchangeability phenomena. The model provides a self-consistent set of response factors for any analyte/matrix combination of any element that appears as either an analyte or matrix in at least one known response factor.

Single n+-i-n+ InP nanowires for highly sensitive terahertz detection.

PubMed

Peng, Kun; Parkinson, Patrick; Gao, Qian; Boland, Jessica L; Li, Ziyuan; Wang, Fan; Mokkapati, Sudha; Fu, Lan; Johnston, Michael B; Tan, Hark Hoe; Jagadish, Chennupati

2017-03-24

Developing single-nanowire terahertz (THz) electronics and employing them as sub-wavelength components for highly-integrated THz time-domain spectroscopy (THz-TDS) applications is a promising approach to achieve future low-cost, highly integrable and high-resolution THz tools, which are desirable in many areas spanning from security, industry, environmental monitoring and medical diagnostics to fundamental science. In this work, we present the design and growth of n + -i-n + InP nanowires. The axial doping profile of the n + -i-n + InP nanowires has been calibrated and characterized using combined optical and electrical approaches to achieve nanowire devices with low contact resistances, on which the highly-sensitive InP single-nanowire photoconductive THz detectors have been demonstrated. While the n + -i-n + InP nanowire detector has a only pA-level response current, it has a 2.5 times improved signal-to-noise ratio compared with the undoped InP nanowire detector and is comparable to traditional bulk THz detectors. This performance indicates a promising path to nanowire-based THz electronics for future commercial applications.

Cluster subgroups based on overall pressure pain sensitivity and psychosocial factors in chronic musculoskeletal pain: Differences in clinical outcomes.

PubMed

Almeida, Suzana C; George, Steven Z; Leite, Raquel D V; Oliveira, Anamaria S; Chaves, Thais C

2018-05-17

We aimed to empirically derive psychosocial and pain sensitivity subgroups using cluster analysis within a sample of individuals with chronic musculoskeletal pain (CMP) and to investigate derived subgroups for differences in pain and disability outcomes. Eighty female participants with CMP answered psychosocial and disability scales and were assessed for pressure pain sensitivity. A cluster analysis was used to derive subgroups, and analysis of variance (ANOVA) was used to investigate differences between subgroups. Psychosocial factors (kinesiophobia, pain catastrophizing, anxiety, and depression) and overall pressure pain threshold (PPT) were entered into the cluster analysis. Three subgroups were empirically derived: cluster 1 (high pain sensitivity and high psychosocial distress; n = 12) characterized by low overall PPT and high psychosocial scores; cluster 2 (high pain sensitivity and intermediate psychosocial distress; n = 39) characterized by low overall PPT and intermediate psychosocial scores; and cluster 3 (low pain sensitivity and low psychosocial distress; n = 29) characterized by high overall PPT and low psychosocial scores compared to the other subgroups. Cluster 1 showed higher values for mean pain intensity (F (2,77)  = 10.58, p < 0.001) compared with cluster 3, and cluster 1 showed higher values for disability (F (2,77)  = 3.81, p = 0.03) compared with both clusters 2 and 3. Only cluster 1 was distinct from cluster 3 according to both pain and disability outcomes. Pain catastrophizing, depression, and anxiety were the psychosocial variables that best differentiated the subgroups. Overall, these results call attention to the importance of considering pain sensitivity and psychosocial variables to obtain a more comprehensive characterization of CMP patients' subtypes.

Measuring the face-sensitive N170 with a gaming EEG system: A validation study.

PubMed

de Lissa, Peter; Sörensen, Sidsel; Badcock, Nicholas; Thie, Johnson; McArthur, Genevieve

2015-09-30

The N170 is a "face-sensitive" event-related potential (ERP) that occurs at around 170ms over occipito-temporal brain regions. The N170's potential to provide insight into the neural processing of faces in certain populations (e.g., children and adults with cognitive impairments) is limited by its measurement in scientific laboratories that can appear threatening to some people. The advent of cheap, easy-to-use portable gaming EEG systems provides an opportunity to record EEG in new contexts and populations. This study tested the validity of the face-sensitive N170 ERP measured with an adapted commercial EEG system (the Emotiv EPOC) that is used at home by gamers. The N170 recorded through both the gaming EEG system and the research EEG system exhibited face-sensitivity, with larger mean amplitudes in response to the face stimuli than the non-face stimuli, and a delayed N170 peak in response to face inversion. The EPOC system produced very similar N170 ERPs to a research-grade Neuroscan system, and was capable of recording face-sensitivity in the N170, validating its use as research tool in this arena. This opens new possibilities for measuring the face-sensitive N170 ERP in people who cannot travel to a traditional ERP laboratory (e.g., elderly people in care), who cannot tolerate laboratory conditions (e.g., people with autism), or who need to be tested in situ for practical or experimental reasons (e.g., children in schools). Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitivity of alpha-particle-driven Alfvén eigenmodes to q-profile variation in ITER scenarios

NASA Astrophysics Data System (ADS)

Rodrigues, P.; Figueiredo, A. C. A.; Borba, D.; Coelho, R.; Fazendeiro, L.; Ferreira, J.; Loureiro, N. F.; Nabais, F.; Pinches, S. D.; Polevoi, A. R.; Sharapov, S. E.

2016-11-01

A perturbative hybrid ideal-MHD/drift-kinetic approach to assess the stability of alpha-particle-driven Alfvén eigenmodes in burning plasmas is used to show that certain foreseen ITER scenarios, namely the {{I}\\text{p}}=15 MA baseline scenario with very low and broad core magnetic shear, are sensitive to small changes in the background magnetic equilibrium. Slight variations (of the order of 1% ) of the safety-factor value on axis are seen to cause large changes in the growth rate, toroidal mode number, and radial location of the most unstable eigenmodes found. The observed sensitivity is shown to proceed from the very low magnetic shear values attained throughout the plasma core, raising issues about reliable predictions of alpha-particle transport in burning plasmas.

Oxygen Sensitivity of Anammox and Coupled N-Cycle Processes in Oxygen Minimum Zones

PubMed Central

Kalvelage, Tim; Jensen, Marlene M.; Contreras, Sergio; Revsbech, Niels Peter; Lam, Phyllis; Günter, Marcel; LaRoche, Julie; Lavik, Gaute; Kuypers, Marcel M. M.

2011-01-01

Nutrient measurements indicate that 30–50% of the total nitrogen (N) loss in the ocean occurs in oxygen minimum zones (OMZs). This pelagic N-removal takes place within only ∼0.1% of the ocean volume, hence moderate variations in the extent of OMZs due to global warming may have a large impact on the global N-cycle. We examined the effect of oxygen (O2) on anammox, NH3 oxidation and NO3 − reduction in 15N-labeling experiments with varying O2 concentrations (0–25 µmol L−1) in the Namibian and Peruvian OMZs. Our results show that O2 is a major controlling factor for anammox activity in OMZ waters. Based on our O2 assays we estimate the upper limit for anammox to be ∼20 µmol L−1. In contrast, NH3 oxidation to NO2 − and NO3 − reduction to NO2 − as the main NH4 + and NO2 − sources for anammox were only moderately affected by changing O2 concentrations. Intriguingly, aerobic NH3 oxidation was active at non-detectable concentrations of O2, while anaerobic NO3 − reduction was fully active up to at least 25 µmol L−1 O2. Hence, aerobic and anaerobic N-cycle pathways in OMZs can co-occur over a larger range of O2 concentrations than previously assumed. The zone where N-loss can occur is primarily controlled by the O2-sensitivity of anammox itself, and not by any effects of O2 on the tightly coupled pathways of aerobic NH3 oxidation and NO3 − reduction. With anammox bacteria in the marine environment being active at O2 levels ∼20 times higher than those known to inhibit their cultured counterparts, the oceanic volume potentially acting as a N-sink increases tenfold. The predicted expansion of OMZs may enlarge this volume even further. Our study provides the first robust estimates of O2 sensitivities for processes directly and indirectly connected with N-loss. These are essential to assess the effects of ocean de-oxygenation on oceanic N-cycling. PMID:22216239

Anxiety Sensitivity and Its Factors in Relation to Generalized Anxiety Disorder among Adolescents.

PubMed

Knapp, Ashley A; Blumenthal, Heidemarie; Mischel, Emily R; Badour, Christal L; Leen-Feldner, Ellen W

2016-02-01

Anxiety psychopathology, one of the most prevalent classes of disorder among youth, is linked to detrimental outcomes. Accordingly, identifying factors that influence vulnerability to anxiety disorders is important. One promising factor, given emerging evidence for its transdiagnostic nature, is anxiety sensitivity (AS); however, relatively little is known about the linkage between AS and indicators of generalized anxiety disorder (GAD), particularly among youth. The aim of the current investigation was to address this gap in the literature using a community-based sample of adolescents aged 10-17 years (n = 165; M age  = 14.49 years, SD = 2.26). Results indicated global AS and the AS-physical concerns dimension were significantly associated with worry, generalized anxiety symptoms, and GAD diagnosis assessed via a structured clinical interview, above and beyond key theoretically-relevant covariates. These findings add to a growing body of work underscoring the relevance of AS for multiple types of anxiety-related disorders among youth.

Normal taste acuity and preference in female adolescents with impaired 6-n-propylthiouracil sensitivity.

PubMed

Nagai, Ayako; Kubota, Masaru; Sakai, Midori; Higashiyama, Yukie

2014-01-01

This study was conducted to determine the relationship between 6-n-propylthiouracil sensitivity and taste characteristics in female students at Nara Women's University. Participants (n=135) were screened for 6-npropylthiouracil sensitivity using a taste test with 0.56 mM 6-n-propylthiouracil solution, and the sensitivity was confirmed by an assay for the bitter-taste receptor gene, TAS2R38. Based on the screening results, 33 6-npropylthiouracil tasters and 21 non-tasters were enrolled. The basic characteristics that are thought to influence taste acuity, including body mass index, saliva volume and serum micronutrient concentrations (iron, zinc and copper), were similar between the two groups. In an analysis using a filter-paper disc method, there were no differences in the acuity for four basic tastes (sweet, salty, sour and bitter) between 6-n-propylthiouracil tasters and non-tasters. In addition, the taste preference for the four basic tastes as measured by a visual analogue scale was also comparable between the two groups. This is the first study to demonstrate that 6-n-propylthiouracil nontasters have taste sensitivity for the four basic tastes similar to that in 6-n-propylthiouracil tasters, at least in female adolescents, as measured by the gustatory test using a filter-paper disc method.

Assessing culturally sensitive factors in the learning environment of science classrooms

NASA Astrophysics Data System (ADS)

Fisher, Darrell L.; Waldrip, Bruce G.

1997-03-01

As schools are becoming increasingly diverse in their scope and clientele, any examination of the interaction of culturally sensitive factors of students' learning environments with learning science assumes critical importance. The purpose of this exploratory study was to develop an instrument to assess learning environment factors that are culturally sensitive, to provide initial validation information on the instrument and to examine associations between students' perceptions of their learning environments and their attitudes towards science and achievement of enquiry skills. A measure of these factors of science student's learning environment, namely the Cultural Learning Environment Questionnaire (CLEQ), was developed from past learning environment instruments and influenced by Hofstede's four dimensions of culture (Power Distance, Uncertainty Avoidance, Individualism, and Masculinity/Femininity). The reliability and discriminant validity for each scale were obtained and associations between learning environment, attitude to science and enquiry skills achievement were found.

Sensitive detection of n-alkanes using a mixed ionization mode proton-transfer-reaction mass spectrometer

NASA Astrophysics Data System (ADS)

Amador-Muñoz, Omar; Misztal, Pawel K.; Weber, Robin; Worton, David R.; Zhang, Haofei; Drozd, Greg; Goldstein, Allen H.

2016-11-01

Proton-transfer-reaction mass spectrometry (PTR-MS) is a technique that is widely used to detect volatile organic compounds (VOCs) with proton affinities higher than water. However, n-alkanes generally have a lower proton affinity than water and therefore proton transfer (PT) by reaction with H3O+ is not an effective mechanism for their detection. In this study, we developed a method using a conventional PTR-MS to detect n-alkanes by optimizing ion source and drift tube conditions to vary the relative amounts of different primary ions (H3O+, O2+, NO+) in the reaction chamber (drift tube). There are very few studies on O2+ detection of alkanes and the mixed mode has never been proposed before. We determined the optimum conditions and the resulting reaction mechanisms, allowing detection of n-alkanes from n-pentane to n-tridecane. These compounds are mostly emitted by evaporative/combustion process from fossil fuel use. The charge transfer (CT) mechanism observed with O2+ was the main reaction channel for n-heptane and longer n-alkanes, while for n-pentane and n-hexane the main reaction channel was hydride abstraction (HA). Maximum sensitivities were obtained at low E / N ratios (83 Td), low water flow (2 sccm) and high O2+ / NO+ ratios (Uso = 180 V). Isotopic 13C contribution was taken into account by subtracting fractions of the preceding 12C ion signal based on the number of carbon atoms and the natural abundance of 13C (i.e., 5.6 % for n-pentane and 14.5 % for n-tridecane). After accounting for isotopic distributions, we found that PT cannot be observed for n-alkanes smaller than n-decane. Instead, protonated water clusters of n-alkanes (M ṡ H3O+) species were observed with higher abundance using lower O2+ and higher water cluster fractions. M ṡ H3O+ species are probably the source for the M + H+ species observed from n-decane to n-tridecane. Normalized sensitivities to O2+ or to the sum of O2++ NO+ were determined to be a good metric with which

N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo.

PubMed

Creager, M A; Roddy, M A; Boles, K; Stamler, J S

1997-02-01

Nitric oxide forms complexes with an array of biomolecular carriers that retain biological activity. This reactivity of nitric oxide in physiological systems has led to some dispute as to whether endothelium-derived relaxing factors nitric oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro bioassays used to address this question are limited by the exclusion of biological thiols that are requisite for nitrosothiol formation. Thus, the purpose of this study was to obtain insight into the identity of endothelium-derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing factor in nitric oxide, infusion of physiological concentrations of thiol would potentiate its bioactivity by analogy with effects seen in vitro, whereas nitrosothiol would be resistant to such modulation. We used venous-occlusion plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3 to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via the brachial artery to elicit endothelium-dependent and endothelium-independent vasodilation, respectively. Dose-response determinations were made for each drug before and after an intra-arterial infusion of the reduced thiol, N-acetylcysteine, at rates estimated to achieve a physiological concentration of 1 mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner. Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7 micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min, P < .01). Thus, conflicting with reports in vitro, thiol does not modulate endothelium-derived relaxing factor responses in vivo. These data indicate that sulfhydryl groups are not a limiting factor for endothelium-derived relaxing factor responses in forearm resistance vessels in normal humans and are in keeping with reports that nitrosothiol

[DNA-dependent DNA polymerase induced by herpes virus papio (HVP) in producing cells].

PubMed

D'iachenko, A G; Beriia, L Ia; Matsenko, L D; Kakubava, V V; Kokosh, L V

1980-11-01

A new DNA polymerase was found in the cells of suspension lymphoblastoid cultures, which produce lymphotropic baboon herpes virus (HVP). The enzyme was isolated in a partially purified form. In some properties the enzyme differs from other cellular DNA polymerases. The HVP-induced DNA polymerase has the molecular weight of 1,6 x 10(5) and sedimentation coefficient of about 8S. The enzyme is resistant to high salt concentrations and N-ethylmaleimide, but shows a pronounced sensitivity to phosphonoacetate. The enzyme effectively copies "activated" DNA and synthetic deoxyribohomopolymers. The attempts to detect the DNA polymerase activity in HVP virions were unsuccessful.

DNA-polymerase induced by Herpesvirus papio (HVP) in cells of lymphoblastoid cultures derived from lymphomatous baboons. Report V.

PubMed

Djachenko, A G; Lapin, B A

1981-01-01

A new DNA-polymerase was found in the cells of suspension lymphoblastoid cultures which produce lymphotropic baboon herpesvirus (HVP). This enzyme was isolated in a partially purified form. Some of its properties vary from those of other cellular DNA-polymerases. HVP-induced DNA-polymerase has a molecule weight of 160,000 and sedimentation coefficient of about 8 S. The enzyme is resistant to high salt concentration and N-ethylmaleimide, but it is very sensitive to phosphonoacetate. It effectively copies "activated" DNA and synthetic deoxyribohomopolymers. Attempts to reveal the DNA-polymerase activity in HVP virions were unsuccessful.

Factor structure and construct validity of the Anxiety Sensitivity Index among island Puerto Ricans.

PubMed

Cintrón, Jennifer A; Carter, Michele M; Suchday, Sonia; Sbrocco, Tracy; Gray, James

2005-01-01

The factor structure and convergent and discriminant validity of the Anxiety Sensitivity Index (ASI) were examined among a sample of 275 island Puerto Ricans. Results from a confirmatory factor analysis (CFA) comparing our data to factor solutions commonly reported as representative of European American and Spanish populations indicated a poor fit. A subsequent exploratory factor analysis (EFA) indicated that a two-factor solution (Factor 1, Anxiety Sensitivity; Factor 2, Emotional Concerns) provided the best fit. Correlations between the ASI and anxiety measures were moderately high providing evidence of convergent validity, while correlations between the ASI and BDI were significantly lower providing evidence of discriminant validity. Scores on all measures were positively correlated with acculturation, suggesting that those who ascribe to more traditional Hispanic culture report elevated anxiety.

Enhancement of electrical and optical performance of N719 by co-sensitization

NASA Astrophysics Data System (ADS)

Shikoh, Ali Sephar; Ahmad, Zubair; Touati, Farid; Al-Muhtaseb, Shaheen A.

2018-04-01

This paper deals with the electrical, optical and electrochemical properties of a metal-free dye C78H74O8 (AS-2), which has been used to improve the photo-detection properties of C58H86N8O8RuS2 (N719) based Dye sensitized photo-sensors (DSPSs). Both dyes were mixed together in various proportions and the most promising ratio N719/AS-2 (1:0.25) was selected for staining photo-anodes for DSPS integration. The fabricated DSPSs were studied in terms of electrical parameters and photodetection properties. The N719/AS-2 (1:0.25) based DSPS were found to have a reduced leakage current, increased breakdown voltage and a closer proximity to an ideal diode, as compared to the N719 based DSPS. Further, the N719/AS-2 (1:0.25) based DSPS was also found to have better linearity at high irradiance levels, thus rendering the co-sensitized device useful as a photosensor in various applications. Electrochemical Impedance Spectroscopy (EIS) analysis was also performed to explain the interfacial charge recombination process.

LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate.

PubMed

Belluzzi, Elisa; Gonnelli, Adriano; Cirnaru, Maria-Daniela; Marte, Antonella; Plotegher, Nicoletta; Russo, Isabella; Civiero, Laura; Cogo, Susanna; Carrion, Maria Perèz; Franchin, Cinzia; Arrigoni, Giorgio; Beltramini, Mariano; Bubacco, Luigi; Onofri, Franco; Piccoli, Giovanni; Greggio, Elisa

2016-01-13

Lrrk2, a gene linked to Parkinson's disease, encodes a large scaffolding protein with kinase and GTPase activities implicated in vesicle and cytoskeletal-related processes. At the presynaptic site, LRRK2 associates with synaptic vesicles through interaction with a panel of presynaptic proteins. Here, we show that LRRK2 kinase activity influences the dynamics of synaptic vesicle fusion. We therefore investigated whether LRRK2 phosphorylates component(s) of the exo/endocytosis machinery. We have previously observed that LRRK2 interacts with NSF, a hexameric AAA+ ATPase that couples ATP hydrolysis to the disassembling of SNARE proteins allowing them to enter another fusion cycle during synaptic exocytosis. Here, we demonstrate that NSF is a substrate of LRRK2 kinase activity. LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling. Substitution of threonine 645 with alanine abrogates LRRK2-mediated increased ATPase activity. Given that the most common Parkinson's disease LRRK2 G2019S mutation displays increased kinase activity, our results suggest that mutant LRRK2 may impair synaptic vesicle dynamics via aberrant phosphorylation of NSF.

Amphiphilic gold nanoparticles as modulators of lipid membrane fusion

NASA Astrophysics Data System (ADS)

Tahir, Mukarram; Alexander-Katz, Alfredo

The fusion of lipid membranes is central to biological functions like inter-cellular transport and signaling and is coordinated by proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) superfamily. We utilize molecular dynamics simulations to demonstrate that gold nanoparticles functionalized with a mixed-monolayer of hydrophobic and hydrophilic alkanethiol ligands can act as synthetic analogues of these fusion proteins and mediate lipid membrane fusion by catalyzing the formation of a toroidal stalk between adjacent membranes and enabling the formation of a fusion pore upon influx of Ca2+ into the exterior solvent. The fusion pathway enabled by these synthetic nanostructures is analogous to the regulated fast fusion pathway observed during synaptic vesicle fusion; it therefore provides novel physical insights into this important biological process while also being relevant in a number of single-cell therapeutic applications. Computational resources from NSF XSEDE contract TG-DMR130042. Financial support from DOE CSGF fellowship DE-FG02-97ER25308.

Commandeering Channel Voltage Sensors for Secretion, Cell Turgor, and Volume Control.

PubMed

Karnik, Rucha; Waghmare, Sakharam; Zhang, Ben; Larson, Emily; Lefoulon, Cécile; Gonzalez, Wendy; Blatt, Michael R

2017-01-01

Control of cell volume and osmolarity is central to cellular homeostasis in all eukaryotes. It lies at the heart of the century-old problem of how plants regulate turgor, mineral and water transport. Plants use strongly electrogenic H + -ATPases, and the substantial membrane voltages they foster, to drive solute accumulation and generate turgor pressure for cell expansion. Vesicle traffic adds membrane surface and contributes to wall remodelling as the cell grows. Although a balance between vesicle traffic and ion transport is essential for cell turgor and volume control, the mechanisms coordinating these processes have remained obscure. Recent discoveries have now uncovered interactions between conserved subsets of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that drive the final steps in secretory vesicle traffic and ion channels that mediate in inorganic solute uptake. These findings establish the core of molecular links, previously unanticipated, that coordinate cellular homeostasis and cell expansion. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overexpression of the Qc-SNARE gene OsSYP71 enhances tolerance to oxidative stress and resistance to rice blast in rice (Oryza sativa L.).

PubMed

Bao, Yong-Mei; Sun, Shu-Jing; Li, Meng; Li, Li; Cao, Wen-Lei; Luo, Jia; Tang, Hai-Juan; Huang, Ji; Wang, Zhou-Fei; Wang, Jian-Fei; Zhang, Hong-Sheng

2012-08-10

OsSYP71 is an oxidative stress and rice blast response gene that encodes a Qc-SNARE protein in rice. Qc-SNARE proteins belong to the superfamily of SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), which function as important components of the vesicle trafficking machinery in eukaryotic cells. In this paper, 12 Qc-SNARE genes were isolated from rice, and expression patterns of 9 genes were detected in various tissues and in seedlings challenged with oxidative stresses and inoculated with rice blast. The expression of OsSYP71 was clearly up-regulated under these stresses. Overexpression of OsSYP71 in rice showed more tolerance to oxidative stress and resistance to rice blast than wild-type plants. These results indicate that Qc-SNAREs play an important role in rice response to environmental stresses, and OsSYP71 is useful in engineering crop plants with enhanced tolerance to oxidative stress and resistance to rice blast. Copyright © 2012 Elsevier B.V. All rights reserved.

Sensitivity of Fermi level position at Ga-polar, N-polar, and nonpolar m-plane GaN surfaces to vacuum and air ambient

NASA Astrophysics Data System (ADS)

Janicki, Łukasz; Ramírez-López, Manolo; Misiewicz, Jan; Cywiński, Grzegorz; Boćkowski, Michał; Muzioł, Grzegorz; Chèze, Caroline; Sawicka, Marta; Skierbiszewski, Czesław; Kudrawiec, Robert

2016-05-01

Ga-polar, N-polar, and nonpolar m-plane GaN UN+ structures have been examined in air and vacuum ambient by contactless electroreflectance (CER). This technique is very sensitive to the surface electric field that varies with the Fermi level position at the surface. For UN+ GaN structures [i.e., GaN (undoped)/GaN (n-type)/substrate], a homogeneous built-in electric field is expected in the undoped GaN layer that is manifested by Franz-Keldysh oscillation (FKO) in CER spectra. A clear change in FKO has been observed in CER spectra for N-polar and nonpolar m-plane structures when changing from air to vacuum ambient. This means that those surfaces are very sensitive to ambient atmosphere. In contrast to that, only a small change in FKO can be seen in the Ga-polar structure. This clearly shows that the ambient sensitivity of the Fermi level position at the GaN surface varies with the crystallographic orientation and is very high for N-polar and nonpolar m-plane surfaces. This feature of the N-polar and nonpolar m-plane surfaces can be very important for GaN-based devices grown on these crystallographic orientations and can be utilized in some of the devices, e.g., sensors.

Characterization of the increased binding of acetaldehyde to red blood cells in alcoholics.

PubMed

Hernández-Muñoz, R; Baraona, E; Blacksberg, I; Lieber, C S

1989-10-01

Using equilibrium dialysis, we found that acetaldehyde, at the levels commonly occurring after ethanol ingestion, did not bind detectably to plasma proteins, but there was significant binding to red blood cells, more in alcoholics than in nonalcoholics. The binding to red blood cells was inhibited by pyridoxal phosphate and N-ethylmaleimide, suggesting adduction to amino and thiol groups. Binding kinetics were consistent with at least two sites. The one with the highest affinity for acetaldehyde corresponded to hemoglobin. Its affinity and Bmax were not changed in alcoholics, but these binding sites accounted for only 44% of the sites available in the red blood cells of alcoholics and 80% of those in controls. Moreover, this binding was not inhibited by N-ethylmaleimide. There was no detectable binding to red cell ghosts. Nonprotein binding was then assessed by changes in NADH produced by the addition of protein-free fractions of the cells to an alcohol dehydrogenase system in equilibrium; this revealed a second binder of lower affinity, larger capacity and with sensitivity to both inhibitors. This binding (possibly due to thiazolidine formation with cysteine) was enhanced in alcoholics, whose red blood cell cysteine content was doubled. Levels of red blood cell cysteine and acetaldehyde remained high for 2 weeks after withdrawal. Because of the prolonged persistence after withdrawal, these changes may provide new markers of alcoholism.

Mechanical sensitivity and psychological factors in patients with burning mouth syndrome.

PubMed

Honda, Mika; Iida, Takashi; Kamiyama, Hirona; Masuda, Manabu; Kawara, Misao; Svensson, Peter; Komiyama, Osamu

2018-05-18

The aim of this study was to compare mechanical sensitivity on the tongue using quantitative sensory testing (QST) and psychological factors using the General Health Questionnaire (GHQ) between burning mouth syndrome (BMS) patients and healthy participants. Participants comprised 20 female BMS patients (68.1 ± 7.4 years) and 20 healthy females (65.4 ± 4.6 years). Psychological factors were evaluated with GHQ. Tactile detection thresholds (TDT) and filament-prick pain detection thresholds (FPT) were used to evaluate mechanical sensitivity on the tongue in all participants. TDT and FPT were measured on the tongue within both the painful area and the non-painful area in BMS patients, and on the tongue on both sides in healthy participants. As controls, TDT and FPT were measured with Semmes-Weinstein monofilaments on the skin of the mentum and palm in all participants. GHQ scores were significantly higher in BMS patients than in healthy participants (P = 0.024). No significant differences in TDT or FPT on the tongue, mentum, or palm were seen between BMS patients and healthy participants (P > 0.05). BMS patients showed no significant differences in TDT or FPT between the painful and non-painful areas on the tongue (P > 0.05). There were no significant correlations among TDT/FPT and GHQ score in BMS patients (P > 0.05). These findings could indicate a more important role for psychological factors than mechanical sensitivity in BMS pathophysiology. Pain on the tongue in elderly female patients with BMS may be more related to psychological factors.

N,N-Diethylamine appended binuclear Zn(ii) complexes: highly selective and sensitive fluorescent chemosensors for picric acid.

PubMed

Kumar, Amit; Kumar, Ashish; Pandey, Daya Shankar

2016-05-28

Novel binuclear Zn(ii) complexes (1-2) derived from bis-chelating salen type ligands (H2L(1) and H2L(2)) possessing N,N-diethylamine moieties on the periphery of the molecules have been synthesized and thoroughly characterized by satisfactory elemental analyses and spectral (FT-IR, (1)H, (13)C NMR, UV-vis, fluorescence and ESI-MS) studies. The structures of H2L(1) and 1 have been authenticated by single crystal X-ray diffraction analyses. Complexes 1 and 2 strongly fluoresce and act as highly selective and sensitive chemosensors for picric acid in different organic as well as aqueous media. Both 1 and 2 showed strong potential to detect traces of PA in vapour/solid phase through contact mode analysis. Spectral and theoretical (DFT) studies suggested that the observed fluorescence quenching may be associated with ground state (GS) charge transfer as well as electrostatic interactions between 1/2 and PA. The fluorescence lifetime for the representative complex 1 displayed a double exponential curve and unaltered lifetime (τav, 0.63 nm) in the absence and presence of PA and strongly suggested that quenching follows a static mechanism. Further, DFT calculations on 1 and 2 strongly supported the static mechanism through GS charge transfer between complexes and PA. In addition, (1)H NMR spectral studies on 1-2 in the presence of PA firmly advocated strong hydrogen bonding and π-π stacking between the phenolic rings of 1-2 and the aromatic ring of PA. These complexes are capable of detecting PA either individually or in a competitive environment of other nitro- explosives. Florescence spectral studies on the model complex M lacking N,N-diethylamine groups revealed moderate selectivity and sensitivity towards PA and supported the key role of N,N-diethylamine moieties in the selectivity and sensitivity of complexes.

Juror sensitivity to false confession risk factors: Dispositional vs. situational attributions for a confession.

PubMed

Woestehoff, Skye A; Meissner, Christian A

2016-10-01

Research on jurors' perceptions of confession evidence suggests that jurors may not be sensitive to factors that can influence the reliability of a confession. Jurors' decisions tend not to be influenced by situational pressures to confess, which suggests that jurors commit the correspondence bias when evaluating a confession. One method to potentially increase sensitivity and counteract the correspondence bias is by highlighting a motivation other than guilt for the defendant's confession. We conducted 3 experiments to evaluate jurors' sensitivity to false confession risk factors. Participants read a trial transcript that varied the presence of false confession risk factors within an interrogation. Some participants also read testimony that presented an alternative motivation for the confession (expert testimony, Experiments 1 and 3; defendant testimony, Experiment 2). Across 3 experiments, participants were generally able to distinguish between interrogation practices that can produce a false confession, regardless of the presence or absence of expert or defendant testimony. Experiment 3 explored whether participants' attributions for the confessor's motivation were affected by interrogative pressure and expert testimony, and whether these attributions affected verdicts. Participants' reluctance to convict when false confession risk factors were present was associated with situational, rather than dispositional, attributions regarding the defendant's motivation to confess. It is possible that increased knowledge is responsible for participants' improved sensitivity to false confession risk factors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Purification and characterization of a polyisoprenyl phosphate phosphatase from pig brain. Possible dual specificity.

PubMed

Frank, D W; Waechter, C J

1998-05-08

Microsomal fractions from pig and calf brain catalyze the enzymatic dephosphorylation of endogenous and exogenous dolichyl monophosphate (Dol-P) (Sumbilla, C. A., and Waechter, C. J. (1985) Methods Enzymol. 111, 471-482). The Dol-P phosphatase (EC 3.1.3.51) has been solubilized by extracting pig brain microsomes with the nonionic detergent Nonidet P-40 and purified approximately 1,107-fold by a combination of anion exchange chromatography, polyethylene glycol fractionation, dye-ligand chromatography, and wheat germ agglutinin affinity chromatography. Treatment of the enzyme with neuraminidase prevented binding to wheat germ agglutinin-Sepharose, indicating the presence of one or more N-acetylneuraminyl residues per molecule of enzyme. When the highly purified polyisoprenyl phosphate phosphatase was analyzed by SDS-polyacrylamide gel electrophoresis, a major 33-kDa polypeptide was observed. Enzymatic dephosphorylation of Dol-P by the purified phosphatase was 1) optimal at pH 7; 2) potently inhibited by F-, orthovanadate, and Zn2+ > Co2+ > Mn2+ but unaffected by Mg2+; 3) exhibited an approximate Km for C95-Dol-P of 45 microM; and 4) was sensitive to N-ethylmaleimide, phenylglyoxal, and diethylpyrocarbonate. The pig brain phosphatase did not dephosphorylate glucose 6-phosphate, mannose 6-phosphate, 5'-AMP, or p-nitrophenylphosphate, but it dephosphorylated dioleoyl-phosphatidic acid at initial rates similar to those determined for Dol-P. Based on the virtually identical sensitivity of Dol-P and phosphatidic acid dephosphorylation by the highly purified enzyme to N-ethylmaleimide, F-, phenylglyoxal, and diethylpyrocarbonate, both substrates appear to be hydrolyzed by a single enzyme with an apparent dual specificity. This is the first report of the purification of a neutral Dol-P phosphatase from mammalian tissues. Although the enzyme is Mg2+-independent and capable of dephosphorylating Dol-P and PA, several enzymological properties distinguish this lipid

N-iodoacetyltyramine: Preparation and use in sup 125 I labeling by alkylation of sulfhydryl groups

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

Lin, C.M.; Mihal, K.A.; Krueger, R.J.

1989-06-01

Preparation and use of N-iodoacetyltyramine in generation of {sup 125}I-labeled compounds is described. The kinetics of alkylation of N-acetylcysteine by N-iodoacetyltyramine (k2 = 3.0 M-1 s-1) and N-chloroacetyltyramine (k2 = 0.12 M-1 s-1) indicate that N-iodoacetyltyramine is more useful for labeling sulfhydryl-containing compounds to high specific activity with {sup 125}I. Conditions for preparation of carrier-free {sup 125}I-labeled N-iodoacetyl-3-monoiodotyramine in 50% yield based on starting iodide are described. The high degree of group specificity of N-iodoacetyl-3-monoiodotyramine reaction with sulfhydryl groups is demonstrated by the high reactivity toward sulfhydryl-containing bovine serum albumin and low reactivity toward N-ethylmaleimide-blocked bovine serum albumin and IgG.more » {sup 125}I-labeled N-iodoacetyl-3-monoiodotyramine was also used to prepare an {sup 125}I-labeled ACTH derivative that retains full biological activity, further demonstrating the selectivity toward reactions with sulfhydryl groups.« less

Differential response of nNOS knockout mice to MDMA ("ecstasy")- and methamphetamine-induced psychomotor sensitization and neurotoxicity.

PubMed

Itzhak, Yossef; Anderson, Karen L; Ali, Syed F

2004-10-01

It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS) gene are resistant to cocaine-induced psychomotor sensitization and methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was undertaken to investigate the hypothesis that nNOS has a major role in dopamine (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)-mediated effects of psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to the psychomotor-stimulating and neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated. Repeated administration of MDMA for 5 days resulted in psychomotor sensitization in both WT and nNOS KO mice, while repeated administration of METH caused psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These findings suggest that the induction of psychomotor sensitization to MDMA and METH is NO independent and NO dependent, respectively, while the persistence of sensitization to both drugs is NO dependent. For the neurochemical studies, a high dose of MDMA caused marked depletion of 5-HT in several brain regions of both WT and KO mice, suggesting that the absence of the nNOS gene did not afford protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic neurotoxicity caused by high doses of MDMA and METH in WT mice was partially prevented in KO mice administered with MDMA, but it was fully precluded in KO mice administered with METH. The differential response of nNOS KO mice to the behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is required for the expression and persistence of DA-mediated effects of METH and MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT depletion) are not dependent on nNOS.

A Bayesian Multi-Level Factor Analytic Model of Consumer Price Sensitivities across Categories

ERIC Educational Resources Information Center

Duvvuri, Sri Devi; Gruca, Thomas S.

2010-01-01

Identifying price sensitive consumers is an important problem in marketing. We develop a Bayesian multi-level factor analytic model of the covariation among household-level price sensitivities across product categories that are substitutes. Based on a multivariate probit model of category incidence, this framework also allows the researcher to…

Risk factors for latex allergy in patients with spina bifida and latex sensitization.

PubMed

Bernardini, R; Novembre, E; Lombardi, E; Mezzetti, P; Cianferoni, A; Danti, D A; Mercurella, A; Vierucci, A

1999-05-01

Some subjects with spina bifida (SB) and latex sensitization (cutaneous and/or serum IgE) can have clinical reactions, while others may have no symptoms after the exposure to latex products. This study was carried out to determine the risk factors associated with latex allergy in patients affected with SB and latex sensitization. Fifty-nine consecutive subjects affected with SB, besides answering a questionnaire, underwent a skin-prick test (SPT) to latex and the determination of the specific serum IgE (RAST CAP) to latex. The total serum IgE concentration was determined and SPT to common aero- and food-allergens, skin tests (prick + prick) with fresh foods (kiwi, pear, orange, pineapple, tomato, banana) and RAST CAP to the same foods tested by the prick + prick technique, were also performed. Fifteen out of the 59 subjects (25%) were sensitized to latex according to the presence of IgE to latex detected by SPT (nine patients) and/or RAST CAP (13 patients). Five out of the 15 sensitized patients (33%) suffered from clinical reactions to latex (urticaria, conjunctivitis, angioedema, rhinitis, bronchial asthma) while they were using latex gloves and while inflating latex balloons. In the 15 sensitized patients, the presence of specific latex seric IgE > 3.5 kU/L (>/= class 3), a positive latex SPT, an elevated total serum IgE, and a positive prick + prick and/or a positive RAST CAP to foods, were significant (P < 0.05) risk factors associated with latex symptoms. The other factors tested (age, gender, months of intermittent bladder catheterization, surgical procedures, SPT reactivity and clinical reactions to aero-allergens and food-allergens, skin tests for fresh foods, positive RAST CAP to foods) were not significantly different in symptomatic and asymptomatic patients. Significant risk factors for symptoms to latex in patients with SB and latex sensitization were a presence of specific IgE to latex > 3.5 kU/L, a more frequent positive latex SPT, elevated total Ig

Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses

PubMed Central

Sinha, Raunak; Ahmed, Saheeb; Jahn, Reinhard; Klingauf, Jurgen

2011-01-01

Exocytosis of synaptic vesicles (SVs) during fast synaptic transmission is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly formed by the coil-coiling of three members of this protein family: vesicle SNARE protein, synaptobrevin 2 (syb2), and the presynaptic membrane SNAREs syntaxin-1A and SNAP-25. However, it is controversially debated how many SNARE complexes are minimally needed for SV priming and fusion. To quantify this effective number, we measured the fluorescence responses from single fusing vesicles expressing pHluorin (pHl), a pH-sensitive variant of GFP, fused to the luminal domain of the vesicular SNARE syb2 (spH) in cultured hippocampal neurons lacking endogenous syb2. Fluorescence responses were quantal, with the unitary signals precisely corresponding to single pHluorin molecules. Using this approach we found that two copies of spH per SV fully rescued evoked fusion whereas SVs expressing only one spH were unable to rapidly fuse upon stimulation. Thus, two syb2 molecules and likely two SNARE complexes are necessary and sufficient for SV fusion during fast synaptic transmission. PMID:21844343

Age, sex and individual differences in punishment sensitivity: factors influencing the feedback-related negativity.

PubMed

Santesso, Diane L; Dzyundzyak, Angela; Segalowitz, Sidney J

2011-11-01

The anterior cingulate cortex (ACC) is central to evaluating performance outcomes and has been linked to individual differences in affective responses to feedback. We used electrophysiological source localization to examine the feedback-related negativity (FRN) and related ACC activity during a gambling task in relation to punishment and reward sensitivity among 16- to 17-year-old adolescents (n=20) and 18- to 29-year-old adults (n=30). The FRN was larger for monetary loss compared to win feedback and larger for high relative to low monetary value feedback, with no age differences in the FRN for win or loss feedback. Self-reported sensitivity to punishment accounted for unique variance (over sex and sensitivity to reward) in FRNs, with higher scores relating to larger FRNs and increased rostral ACC activity. These results support the ACC role in experiencing negative performance feedback, especially for individuals highly sensitive to punishment. Copyright © 2011 Society for Psychophysiological Research.

Spectral sensitivity characteristics simulation for silicon p-i-n photodiode

NASA Astrophysics Data System (ADS)

Urchuk, S. U.; Legotin, S. A.; Osipov, U. V.; Elnikov, D. S.; Didenko, S. I.; Astahov, V. P.; Rabinovich, O. I.; Yaromskiy, V. P.; Kuzmina, K. A.

2015-11-01

In this paper the simulation results of the spectral sensitivity characteristics of silicon p-i-n-photodiodes are presented. The analysis of the characteristics of the semiconductor material (the doping level, lifetime, surface recombination velocity), the construction and operation modes on the characteristics of photosensitive structures in order to optimize them was carried out.

Exploration of anxiety sensitivity and distress tolerance as vulnerability factors for hoarding behaviors.

PubMed

Timpano, Kiara R; Buckner, Julia D; Richey, J Anthony; Murphy, Dennis L; Schmidt, Norman B

2009-01-01

The phenomenon of compulsive hoarding, characterized by the acquisition of and failure to discard a large number of possessions, is increasingly recognized as a significant public health burden. Despite the magnitude of the impairment associated with this condition, empirical research is still in the nascent stages and many facets of the phenomenology, underlying vulnerability and risk factors for hoarding, are as of yet unknown. The overall aim of the current investigation was to examine the association between hoarding behaviors and two potential vulnerability factors-anxiety sensitivity (AS) and distress tolerance (DT). In addition, we investigated the robustness of these associations as well as the interaction between the two hypothesized risk factors. Three studies (total N=745) involving independent nonclinical samples assessed hoarding, AS, DT, and relevant covariates using a range of measures. Resutlts: Findings revealed that AS and hoarding are significantly and robustly associated with one another beyond general depressive, anxiety, and nonhoarding obsessive-compulsive symptoms. Hoarding was also found to be associated with low DT. Consistent with prediction, AS and DT interacted such that DT may play a less important role among individuals with low AS. By contrast, low DT appears to increase vulnerability to hoarding symptoms among individuals high in AS. Results are discussed with regard to future research and treatment implications. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc.

Factors associated with allergen sensitizations in patients with asthma and/or rhinitis in China.

PubMed

Li, Jing; Huang, Ying; Lin, Xiaoping; Zhao, Deyu; Tan, Guolin; Wu, Jinzhun; Zhao, Changqing; Zhao, Jing; Spangfort, Michael D; Lai, Xuxin; Zhong, Nanshan

2012-01-01

Allergen sensitization is influenced by genetic and environmental factors; however, the factors related to sensitizations in patients with rhinitis and asthma in China are largely unknown. This study investigated the factors associated with allergen sensitizations in patients with asthma and rhinitis in China. A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from four regions of China. Patients completed a standardized questionnaire related to respiratory and allergic symptoms, family history of allergic diseases, smoking history, environmental exposure, and eating behaviors. They underwent skin-prick tests (SPTs) with 13 common aeroallergens. Blood samples were collected from 2268 of patients for specific IgE (sIgE) measurements against 16 common aeroallergens. Patients with both asthma and rhinitis had higher prevalence of SPT and sIgE positivity to most allergens than those with asthma or rhinitis alone (p < 0.0001). Male gender, family history of allergic rhinitis, air-conditioner usage, sleeping on a mattress, and frequently eating meat were associated with increased risk of SPT and sIgE positivity. Using air-conditioner and sleeping on a mattress were further found to be associated with sIgE positivity to mites and molds. However, increased age and fish, fruit, and raw vegetable intake decreased the risk of SPT and sIgE positivity. Family history of allergic rhinitis, male gender, using an air conditioner, sleeping on a mattress, and frequent meat consumption are risk factors for allergen sensitizations, whereas increased age and frequent fish, fruit, and raw vegetable consumption may protect patients with asthma and/or rhinitis from developing sensitizations in China.

Interparental Violence and Childhood Adjustment: How and Why Maternal Sensitivity is a Protective Factor

PubMed Central

Manning, Liviah G.; Davies, Patrick T.; Cicchetti, Dante

2014-01-01

This study examined sensitive parenting as a protective factor in relations between interparental violence and children’s coping and psychological adjustment. Using a multi-method approach, a high risk sample of 201 two-year olds and their mothers participated in three annual waves of data collection. Moderator analyses revealed that sensitive parenting buffered the risk posed by interparental violence on children’s changes in externalizing and prosocial development over a two year period. Tests of mediated moderation further indicated that sensitive parenting protected children from the vulnerability of growing up in a violent home through its association with lower levels of children’s angry reactivity to interparental conflict. Results highlight the significance of identifying the mechanisms that mediate protective factors in models of family adversity. PMID:25132541

Low susceptibility of NC/Nga mice to tumor necrosis factor-alpha-mediated lethality and hepatocellular damage with D-galactosamine sensitization.

PubMed

Koide, Naoki; Morikawa, Akiko; Naiki, Yoshikazu; Tumurkhuu, Gantsetseg; Yoshida, Tomoaki; Ikeda, Hiroshi; Yokochi, Takashi

2009-02-01

The susceptibility of NC/Nga mice to tumor necrosis factor (TNF)-alpha was examined by using sensitization with d-galactosamine (d-GalN). Administration of TNF-alpha and d-GalN killed none of the NC/Nga mice, whereas it killed all of the BALB/c mice. Treatment with TNF-alpha and d-GalN caused few hepatic lesions in NC/Nga mice but massive hepatocellular apoptosis in BALB/c mice. Unlike BALB/c mice, there was no elevation in caspase 3 and 8 activities in the livers of NC/Nga mice receiving TNF-alpha and d-GalN. On the other hand, administration of anti-Fas antibody definitely killed both NC/Nga and BALB/c mice via activation of caspases 3 and 8. Treatment with TNF-alpha and d-GalN led to translocation of nuclear factor (NF)-kappaB in NC/Nga and BALB/c mice. However, NF-kappaB translocation was sustained in NC/Nga mice, although it disappeared in BALB/c mice 7 h after the treatment. NF-kappaB inhibitors activated caspases 3 and 8, and enhanced TNF-alpha-mediated lethality in NC/Nga. Taken together, the low susceptibility of NC/Nga mice to TNF-alpha-mediated lethality was suggested to be responsible for the sustained NF-kappaB activation.

Morphine Antidependence of Erythroxylum cuneatum (Miq.) Kurz in Neurotransmission Processes In Vitro

PubMed Central

Adenan, Mohd Ilham; Amom, Zulkhairi

2016-01-01

Opiate abuse has been studied to cause adaptive changes observed in the presynaptic release and the mediated-synaptic plasticity proteins. The involvement of neuronal SNARE proteins reveals the role of the neurotransmitter release in expressing the opioid actions. The present study was designed to determine the effect of the alkaloid extract of Erythroxylum cuneatum (E. cuneatum) against chronic morphine and the influences of E. cuneatum on neurotransmission processes observed in vitro. The human neuroblastoma cell line, SK-N-SH, was treated with the morphine, methadone, or E. cuneatum. The cell lysates were collected and tested for α-synuclein, calmodulin, vesicle-associated membrane protein 2 (VAMP 2), and synaptotagmin 1. The extract of E. cuneatum was observed to upregulate the decreased expression of dependence proteins, namely, α-synuclein and calmodulin. The effects were comparable to methadone and control. The expressions of VAMP 2 and synaptotagmin 1 were normalised by the plant and methadone. The extract of E. cuneatum was postulated to treat dependence symptoms after chronic morphine and improve the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) protein involved in synaptic vesicle after. PMID:27974903

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling

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

Kumar G.; Swaminathan S.; Kumaran, D.

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC{sub 50} of 0.9 {micro}M and a K{sub i} ofmore » 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.« less

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling.

PubMed

Kumar, Gyanendra; Kumaran, Desigan; Ahmed, S Ashraf; Swaminathan, Subramanyam

2012-05-01

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC(50) of 0.9 µM and a K(i) of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features. © 2012 International Union of Crystallography

An approximately factored incremental strategy for calculating consistent discrete aerodynamic sensitivity derivatives

NASA Technical Reports Server (NTRS)

Korivi, V. M.; Taylor, A. C., III; Newman, P. A.; Hou, G. J.-W.; Jones, H. E.

1992-01-01

An incremental strategy is presented for iteratively solving very large systems of linear equations, which are associated with aerodynamic sensitivity derivatives for advanced CFD codes. It is shown that the left-hand side matrix operator and the well-known factorization algorithm used to solve the nonlinear flow equations can also be used to efficiently solve the linear sensitivity equations. Two airfoil problems are considered as an example: subsonic low Reynolds number laminar flow and transonic high Reynolds number turbulent flow.

Effect of Macrophage Migration Inhibitory Factor on Corneal Sensitivity after Laser In Situ Keratomileusis in Rabbit

PubMed Central

Hose, Stacey; Gongora, Celine; Sinha, Debasish; O'Brien, Terrence

2014-01-01

Purpose To investigate the effect of macrophage migration inhibitory factor (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery. Methods New Zealand white rabbits were used in this study. A hinged corneal flap (160-µm thick) was created with a microkeratome, and -3.0 diopter excimer laser ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells and surrounding inflammatory cells were analyzed using reverse transcription polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL), neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed using the Cochet-Bonnet esthesiometer. Results Expression of MIF mRNA was 2.5-fold upregulated in the corneal epithelium and 1.5-fold upregulated in the surrounding inflammatory cells as compared with the control eyes. Preoperative baseline corneal sensitivity was 40.56 ± 2.36 mm. At two weeks after LASIK, corneal sensitivity was 9.17 ± 5.57 mm in the BSS treated group, 21.92 ± 2.44 mm in the MIF treated group, and 22.42 ± 1.59 mm in the neuronal growth factors-treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK, corneal sensitivity was 15.00 ± 9.65, 35.00 ± 5.48, and 29.58 ± 4.31 mm respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone could achieve as much of an effect on recovery of corneal sensation as treatment with combination of NGF, NT-3, IL-6, and LIF. Conclusions Topically administered MIF plays a significant role in the

Effect of macrophage migration inhibitory factor on corneal sensitivity after laser in situ keratomileusis in rabbit.

PubMed

Hyon, Joon Young; Hose, Stacey; Gongora, Celine; Sinha, Debasish; O'Brien, Terrence

2014-04-01

To investigate the effect of macrophage migration inhibitory factor (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery. New Zealand white rabbits were used in this study. A hinged corneal flap (160-µm thick) was created with a microkeratome, and -3.0 diopter excimer laser ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells and surrounding inflammatory cells were analyzed using reverse transcription polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL), neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed using the Cochet-Bonnet esthesiometer. Expression of MIF mRNA was 2.5-fold upregulated in the corneal epithelium and 1.5-fold upregulated in the surrounding inflammatory cells as compared with the control eyes. Preoperative baseline corneal sensitivity was 40.56 ± 2.36 mm. At two weeks after LASIK, corneal sensitivity was 9.17 ± 5.57 mm in the BSS treated group, 21.92 ± 2.44 mm in the MIF treated group, and 22.42 ± 1.59 mm in the neuronal growth factors-treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK, corneal sensitivity was 15.00 ± 9.65, 35.00 ± 5.48, and 29.58 ± 4.31 mm respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone could achieve as much of an effect on recovery of corneal sensation as treatment with combination of NGF, NT-3, IL-6, and LIF. Topically administered MIF plays a significant role in the early recovery of corneal

[Psychosocial stressors and pain sensitivity in chronic pain disorder with somatic and psychological factors (F45.41)].

PubMed

Studer, M; Stewart, J; Egloff, N; Zürcher, E; von Känel, R; Brodbeck, J; Grosse Holtforth, M

2017-02-01

Increased pain sensitivity is characteristic for patients with chronic pain disorder with somatic and psychological factors (F45.41). Persistent stress can induce, sustain, and intensify pain sensitivity, thereby modulating pain perception. In this context, it would be favorable to investigate which psychosocial stressors are empirically linked to pain sensitivity. The aim of this study was to examine the relationship between psychosocial stressors and pain sensitivity in a naturalistic sample of patients with chronic pain disorder with somatic and psychological factors (F45.41). We assessed 166 patients with chronic pain disorder with somatic and psychological factors (F45.41) at entry into an inpatient pain clinic. Pain sensitivity was measured with a pain provocation test (Algopeg) at the middle finger and earlobe. Stressors assessed were exposure to war experiences, adverse childhood experiences, illness-related inability to work, relationship problems, and potentially life-threatening accidents. Correlation analyses and structural equation modeling were used to examine which stressors showed the strongest prediction of pain sensitivity. Patients exhibited generally heightened pain sensitivity. Both exposure to war and illness-related inability to work showed significant bivariate correlations with pain sensitivity. In addition to age, they also predicted a further increase in pain sensitivity in the structural equation model. Bearing in mind the limitations of this cross-sectional study, these findings may contribute to a better understanding of the link between psychosocial stressors and pain sensitivity.

Influence of interaction of environmental risk factors and sensitization in young asthmatic children.

PubMed

Lindfors, A; van Hage-Hamsten, M; Rietz, H; Wickman, M; Nordvall, S L

1999-10-01

The increasing prevalence of asthma and allergy in many countries demands evaluation of potential risk factors to improve the possibility of prevention. We studied the association between exposure to cat and dog allergen and allergic sensitization in young children with asthma and interactions with potential environmental risk factors. One hundred eighty-nine young children with asthma were evaluated. IgE antibodies to cat and dog were analyzed. Questionnaires were filled in focusing on exposure to cats and dogs, environmental tobacco smoke (ETS), and signs of home dampness as indicated by window pane condensation (WPC) during the first years of life. House dust was analyzed for content of cat (Fel d 1) and dog (Can f 1) allergen. There was a strong association between the degree of reported exposure to cat and dog and the concentration of the respective allergens in floor dust. A dose-response relationship was found between cat exposure, measured as either reported degree of cat exposure or cat allergen levels in dust, and sensitization both to cat and dog. No such relationship was found between exposure and sensitization to dog. WPC increased the risk for sensitization to cat (odds ratio = 2.6, 95% confidence interval 1.2-5.8), whereas ETS strongly tended to do so both to cat and dog. Interaction was found between exposure to ETS, WPC, and high levels of cat allergen (>8 microg/g dust). The presence of all 3 risk factors revealed a multiplicative interaction with a high risk of sensitization to cat (odds ratio = 42.0, 95% confidence interval 3.7-472.8). Keeping cats indoors may be a health hazard for infants and young children at risk for development of asthma, particularly when they live in a damp house and their parents smoke.

Current status of the thiol redox model for the regulation of hexose transport by insulin.

PubMed

Czech, M P

1976-12-01

Data obtained over the last two years pertinent to the thiol redox model for the modulation of hexose transport activity by insulin is summarized. The model proposes that activation of hexose transport in fat cells involves sulfhydryl oxidation to the disulfide form in a key protein component of the fat cell surface membrane. Theoretically, the rapid activation of transport by insulin may involve either the conversion of inactive membrane carriers to the active form as originally proposed, or the conversion of a low Vmax transport system to a high Vmax form. The present experiments showed that the percent inhibition of insulin-activated transport rates by submaximal levels of cytochalasin B was decreased compared to its effects on basal transport. Treatment of fat cells with N-ethylmaleimide inhibited cytochalasin B action but not transport activity. When insulin or the oxidant vitamin K5 was added to cells 5 minutes before the N-ethylmaleimide, the elevated transport activity was also resistant to the sulfhydryl reagent, but cytochalasin B retained its potent inhibitory effect on transport. The data demonstrate that unique properties characterize basal versus insulin-activated transport activity with respect to the sensitivity of cytochalasin B action to sulfhydryl blockade in isolated fat cells. The data are consistent with the concept that activation of transport activity reflects the conversion of a reduced (sulfhydryl) system characterized by a low Vmax to an oxidized (disulfide), high Vmax transport system.

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2)*

PubMed Central

Elguindy, Mahmoud M.; Nakamaru-Ogiso, Eiko

2015-01-01

Apoptosis-inducing factor (AIF) and AMID (AIF-homologous mitochondrion-associated inducer of death) are flavoproteins. Although AIF was originally discovered as a caspase-independent cell death effector, bioenergetic roles of AIF, particularly relating to complex I functions, have since emerged. However, the role of AIF in mitochondrial respiration and redox metabolism has remained unknown. Here, we investigated the redox properties of human AIF and AMID by comparing them with yeast Ndi1, a type 2 NADH:ubiquinone oxidoreductase (NDH-2) regarded as alternative complex I. Isolated AIF and AMID containing naturally incorporated FAD displayed no NADH oxidase activities. However, after reconstituting isolated AIF or AMID into bacterial or mitochondrial membranes, N-terminally tagged AIF and AMID displayed substantial NADH:O2 activities and supported NADH-linked proton pumping activities in the host membranes almost as efficiently as Ndi1. NADH:ubiquinone-1 activities in the reconstituted membranes were highly sensitive to 2-n-heptyl-4-hydroxyquinoline-N-oxide (IC50 = ∼1 μm), a quinone-binding inhibitor. Overexpressing N-terminally tagged AIF and AMID enhanced the growth of a double knock-out Escherichia coli strain lacking complex I and NDH-2. In contrast, C-terminally tagged AIF and NADH-binding site mutants of N-terminally tagged AIF and AMID failed to show both NADH:O2 activity and the growth-enhancing effect. The disease mutant AIFΔR201 showed decreased NADH:O2 activity and growth-enhancing effect. Furthermore, we surprisingly found that the redox activities of N-terminally tagged AIF and AMID were sensitive to rotenone, a well known complex I inhibitor. We propose that AIF and AMID are previously unidentified mammalian NDH-2 enzymes, whose bioenergetic function could be supplemental NADH oxidation in cells. PMID:26063804

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2).

PubMed

Elguindy, Mahmoud M; Nakamaru-Ogiso, Eiko

2015-08-21

Apoptosis-inducing factor (AIF) and AMID (AIF-homologous mitochondrion-associated inducer of death) are flavoproteins. Although AIF was originally discovered as a caspase-independent cell death effector, bioenergetic roles of AIF, particularly relating to complex I functions, have since emerged. However, the role of AIF in mitochondrial respiration and redox metabolism has remained unknown. Here, we investigated the redox properties of human AIF and AMID by comparing them with yeast Ndi1, a type 2 NADH:ubiquinone oxidoreductase (NDH-2) regarded as alternative complex I. Isolated AIF and AMID containing naturally incorporated FAD displayed no NADH oxidase activities. However, after reconstituting isolated AIF or AMID into bacterial or mitochondrial membranes, N-terminally tagged AIF and AMID displayed substantial NADH:O₂ activities and supported NADH-linked proton pumping activities in the host membranes almost as efficiently as Ndi1. NADH:ubiquinone-1 activities in the reconstituted membranes were highly sensitive to 2-n-heptyl-4-hydroxyquinoline-N-oxide (IC₅₀ = ∼1 μm), a quinone-binding inhibitor. Overexpressing N-terminally tagged AIF and AMID enhanced the growth of a double knock-out Escherichia coli strain lacking complex I and NDH-2. In contrast, C-terminally tagged AIF and NADH-binding site mutants of N-terminally tagged AIF and AMID failed to show both NADH:O₂ activity and the growth-enhancing effect. The disease mutant AIFΔR201 showed decreased NADH:O₂ activity and growth-enhancing effect. Furthermore, we surprisingly found that the redox activities of N-terminally tagged AIF and AMID were sensitive to rotenone, a well known complex I inhibitor. We propose that AIF and AMID are previously unidentified mammalian NDH-2 enzymes, whose bioenergetic function could be supplemental NADH oxidation in cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Microwave based synthesis and spectral characterization of thermo-sensitive poly(N,N-diethylacrylamide) grafted pectin copolymer.

PubMed

Işıklan, Nuran; Tokmak, Şeyma

2018-07-01

The functionalization of polysaccharides with synthetic polymers has attracted great attention owing to its application in many industrial fields. The aim of this work was to study the impact of pectin functionalization with N,N-diethylacrylamide (DEAAm). Pectin was modified via microwave-induced graft copolymerization of DEAAm using ceric ammonium nitrate (CAN) and N,N,N',N'-tetramethylethylenediamine (TEMED). FTIR, 13 C NMR, DSC/TGA, XRD, and SEM techniques were used to verify the structure of graft copolymers. Various reaction conditions such as microwave irradiation time, temperature, microwave power, monomer, initiator, and TEMED concentrations were investigated to get a maximum grafting yield of 192%. Lower critical solution temperatures (LCST) of graft copolymers were determined by UV spectroscopy. Graft copolymers were found to be thermo-sensitive, with LCST of 31°C and high thermal resistance. Biocompatibility test of copolymers showed that copolymers were not cytotoxic to L929 fibroblasts cells and can be used as a biomaterial. Copyright © 2018 Elsevier B.V. All rights reserved.

Highly Sensitive Detection of Deoxyribonucleic Acid Hybridization Using Au-Gated AlInN/GaN High Electron Mobility Transistor-Based Sensors

NASA Astrophysics Data System (ADS)

Zhan, Xiang-Mi; Hao, Mei-Lan; Wang, Quan; Li, Wei; Xiao, Hong-Ling; Feng, Chun; Jiang, Li-Juan; Wang, Cui-Mei; Wang, Xiao-Liang; Wang, Zhan-Guo

2017-03-01

Gallium nitride- (GaN) based high electron mobility transistors (HEMTs) provide a good platform for biological detection. In this work, both Au-gated AlInN/GaN HEMT and AlGaN/GaN HEMT biosensors are fabricated for the detection of deoxyribonucleic acid (DNA) hybridization. The Au-gated AlInN/GaN HEMT biosensor exhibits higher sensitivity in comparison with the AlGaN/GaN HEMT biosensor. For the former, the drain-source current ( {V}{DS}=0.5 V) shows a clear decrease of 69 μA upon the introduction of 1 μmolL {}-1 (μM) complimentary DNA to the probe DNA at the sensor area, while for the latter it is only 38 μA. This current reduction is a notable indication of the hybridization. The high sensitivity can be attributed to the thinner barrier of the AlInN/GaN heterostructure, which makes the two-dimensional electron gas channel more susceptible to a slight change of the surface charge. Supported by the National Key Research and Development Program of China under Grant Nos 2016YFB0400104 and 2016YFB0400301, the National Natural Sciences Foundation of China under Grant No 61334002, and the National Science and Technology Major Project.

N270 sensitivity to conflict strength and working memory: A combined ERP and sLORETA study.

PubMed

Scannella, Sébastien; Pariente, Jérémie; De Boissezon, Xavier; Castel-Lacanal, Evelyne; Chauveau, Nicolas; Causse, Mickaël; Dehais, Frédéric; Pastor, Josette

2016-01-15

The event-related potential N270 component is known to be an electrophysiological marker of the supramodal conflict processing. However little is know about the factors that may modulate its amplitude. In particular, among all studies that have investigated the N270, little or no control of the conflict strength and of the load in working memory have been done leaving a lack in the understanding of this component. We designed a spatial audiovisual conflict task with simultaneous target and cross-modal distractor to evaluate the N270 sensitivity to the conflict strength (i.e., visual target with auditory distractor or auditory target with visual distractor) and the load in working memory (goal task maintenance with frequent change in the target modality). In a first session, participants had to focus on one modality for the target position to be considered (left-hand or right-hand) while the distractor could be at the same side (compatible) or at opposite side (incompatible). In a second session, we used the same set of stimuli as in the first session with an additional distinct auditory signal that clued the participants to frequently switch between the auditory and the visual targets. We found that (1) reaction times and N270 amplitudes for conflicting situations were larger within the auditory target condition compared to the visual one, (2) the increase in target maintenance effort led to equivalent increase of both reaction times and N270 amplitudes within all conditions and (3) the right dorsolateral prefrontal cortex current density was higher for both conflicting and active maintenance of the target situations. These results provide new evidence that the N270 component is an electrophysiological marker of the supramodal conflict processing that is sensitive to the conflict strength and that conflict processing and active maintenance of the task goal are two functions of a common executive attention system. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of immersion cycles during n-β-Bi2O3 sensitization on the photoelectrochemical behaviour of N-F-codoped TiO2 nanotubes

NASA Astrophysics Data System (ADS)

Hoyos, Lina J.; Rivera, Diego F.; Gualdrón-Reyes, Andrés F.; Ospina, Rogelio; Rodríguez-Pereira, Jhonatan; Ropero-Vega, Jose L.; Niño-Gómez, Martha E.

2017-11-01

Sensitization of TiO2 nanotube (TNT)-based photoanodes with narrow-band gap semiconductors is an important alternative to improving the photoelectrochemical properties of the material. However, the interaction between the sensitizer and TNT is not understood deeply enough to relate charge carrier transport into the composite photoanode with its photoactivity. In this contribution, we studied the photoelectrochemical behaviour of N-F-self codoped TiO2 nanotubes (N-F-TNTs) that were grown by anodization of titanium plates and sensitized with β-Bi2O3 by immersing the TNTs into a Bi2O3 sol solution by dip-coating. The number of immersion cycles was varied. The as-fabricated photoanodes were characterized by FESEM, GIXRD, DRS and XPS, while their photoelectrochemical and semiconducting properties were investigated by photovoltammetry, electrochemical impedance spectroscopy and Mott-Schottky analysis in 0.1 M HClO4. The photoelectrocatalytic activity of the composite photoanodes was evaluated for glycerol oxidation under acidic and alkaline conditions. The N-F-TNTs exhibit a well-oriented structure after β-Bi2O3 deposition. The presence of substitutions of both N and F, identified by XPS, indicates the self-doping of the TNTs during anodization. The visible-light harvesting of the N-F-TNT photoanode was enhanced after three -immersion cycles during β-Bi2O3 sensitization, establishing an adequate n-n heterojunction at the N-F-TNT/Bi2O3 interface. In addition, bismuth migration from the sensitizer to the TNT lattice was promoted during thermal treatment, forming Bi-N-F-tridoping of TNT (Bi-N-F-TNT). The suitable band alignment between TNT and β-Bi2O3 and incorporation of the Bi3+ energy levels into TiO2 facilitate charge carrier separation and electron transport throughout the cell. Nevertheless, increasing the number of immersion cycles over three creates an excess of Bi3+ species at the N-F-TNT/β-Bi2O3 interface, producing an energetic barrier that hinders electron

Long-term reproducibility of relative sensitivity factors obtained with CAMECA Wf

NASA Astrophysics Data System (ADS)

Gui, D.; Xing, Z. X.; Huang, Y. H.; Mo, Z. Q.; Hua, Y. N.; Zhao, S. P.; Cha, L. Z.

2008-12-01

As the wafer size continues to increase and the feature size of the integrated circuits (IC) continues to shrink, process control of IC manufacturing becomes ever more important to reduce the cost of failures caused by the drift of processes or equipments. Characterization tools with high precision and reproducibility are required to capture any abnormality of the process. Although Secondary ion mass spectrometry (SIMS) has been widely used in dopant profile control, it was reported that magnetic sector SIMS, compared to quadrupole SIMS, has lower short-term repeatability and long-term reproducibility due to the high extraction field applied between sample and extraction lens. In this paper, we demonstrate that CAMECA Wf can deliver high long-term reproducibility because of its high-level automation and improved design of immersion lens. The relative standard deviation (R.S.D.) of the relative sensitivity factors (RSF) of three typical elements, i.e., boron (B), phosphorous (P) and nitrogen (N), over 3 years are 3.7%, 5.5% and 4.1%, respectively. The high reproducibility results have a practical implication that deviation can be estimated without testing the standards.

Taxometric and Factor Analytic Models of Anxiety Sensitivity: Integrating Approaches to Latent Structural Research

ERIC Educational Resources Information Center

Bernstein, Amit; Zvolensky, Michael J.; Norton, Peter J.; Schmidt, Norman B.; Taylor, Steven; Forsyth, John P.; Lewis, Sarah F.; Feldner, Matthew T.; Leen-Feldner, Ellen W.; Stewart, Sherry H.; Cox, Brian

2007-01-01

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), as indexed by the 16-item Anxiety Sensitivity Index (ASI; S. Reiss, R. A. Peterson, M. Gursky, & R. J. McNally, 1986), by using taxometric and factor-analytic approaches in an integrative manner. Taxometric analyses indicated that AS has a…

Factors influencing antibiotic prescribing habits and use of sensitivity testing amongst veterinarians in Europe.

PubMed

De Briyne, N; Atkinson, J; Pokludová, L; Borriello, S P; Price, S

2013-11-16

The Heads of Medicines Agencies and the Federation of Veterinarians of Europe undertook a survey to gain a better insight into the decision-making process of veterinarians in Europe when deciding which antibiotics to prescribe. The survey was completed by 3004 practitioners from 25 European countries. Analysis was to the level of different types of practitioner (food producing (FP) animals, companion animals, equines) and country for Belgium, Czech Republic, France, Germany, Spain, Sweden and the UK. Responses indicate no single information source is universally considered critical, though training, published literature and experience were the most important. Factors recorded which most strongly influenced prescribing behaviour were sensitivity tests, own experience, the risk for antibiotic resistance developing and ease of administration. Most practitioners usually take into account responsible use warnings. Antibiotic sensitivity testing is usually performed where a treatment failure has occurred. Significant differences were observed in the frequency of sensitivity testing at the level of types of practitioners and country. The responses indicate a need to improve sensitivity tests and services, with the availability of rapid and cheaper testing being key factors.

Factors influencing antibiotic prescribing habits and use of sensitivity testing amongst veterinarians in Europe

PubMed Central

De Briyne, N.; Atkinson, J.; Pokludová, L.; Borriello, S. P.; Price, S.

2013-01-01

The Heads of Medicines Agencies and the Federation of Veterinarians of Europe undertook a survey to gain a better insight into the decision-making process of veterinarians in Europe when deciding which antibiotics to prescribe. The survey was completed by 3004 practitioners from 25 European countries. Analysis was to the level of different types of practitioner (food producing (FP) animals, companion animals, equines) and country for Belgium, Czech Republic, France, Germany, Spain, Sweden and the UK. Responses indicate no single information source is universally considered critical, though training, published literature and experience were the most important. Factors recorded which most strongly influenced prescribing behaviour were sensitivity tests, own experience, the risk for antibiotic resistance developing and ease of administration. Most practitioners usually take into account responsible use warnings. Antibiotic sensitivity testing is usually performed where a treatment failure has occurred. Significant differences were observed in the frequency of sensitivity testing at the level of types of practitioners and country. The responses indicate a need to improve sensitivity tests and services, with the availability of rapid and cheaper testing being key factors. PMID:24068699

The contribution of reinforcement sensitivity to the personality-psychopathology hierarchical structure in childhood and adolescence.

PubMed

Slobodskaya, Helena R

2016-11-01

This study examined the contribution of reinforcement sensitivity to the hierarchical structure of child personality and common psychopathology in community samples of parent reports of children aged 2-18 (N = 968) and self-reports of adolescents aged 10-18 (N = 1,543) using the Inventory of Child Individual Differences-Short version (ICID-S), the Strengths and Difficulties Questionnaire (SDQ), and the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ). A joint higher-order factor analysis of the ICID-S and SDQ scales suggested a 4-factor solution; congruence coefficients indicated replicability of the factors across the 2 samples at all levels of the personality-psychopathology hierarchy. The canonical correlation analyses indicated that reinforcement sensitivity and personality-psychopathology dimensions shared much of their variance. The main contribution of reinforcement sensitivity was through opposing effects of reward and punishment sensitivities. The superordinate factors Beta and Internalizing were best predicted by reinforcement sensitivity, followed by the Externalizing and Positive personality factors. These findings provide evidence for consistency of the hierarchical structure of personality and common psychopathology across informants and highlight the role of reinforcement systems in the development of normal and abnormal patterns of behavior and affect. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Anxiety Sensitivity, Experiential Avoidance, and Mindfulness Among Younger and Older Adults: Age Differences in Risk Factors for Anxiety Symptoms.

PubMed

Mahoney, Colin T; Segal, Daniel L; Coolidge, Frederick L

2015-10-01

In this cross-sectional study, we examined age-related differences in anxiety sensitivity (AS), experiential avoidance (EA), and mindfulness among younger adult students (N=426; M age=20.1 years) and community-dwelling older adults (N=85; M age=71.8 years). Participants anonymously completed the Anxiety Sensitivity Index-3, Acceptance and Action Questionnaire-II, Mindful Attention Awareness Scale, Kentucky Inventory of Mindfulness Skills, Beck Anxiety Inventory, Geriatric Anxiety Scale, and State-Trait Anxiety Inventory. Independent t tests indicated that younger adults reported significantly higher levels of AS and EA, whereas older adults reported significantly higher levels of trait mindfulness. Correlational analyses demonstrated that AS and EA were significantly associated with each other and with anxiety-related symptoms. However, trait mindfulness was significantly inversely related to AS, EA, and to trait and state anxiety. To date, these three factors have yet to be examined simultaneously within the context of age differences, and the present study illuminates these differences as well as their relationships. AS, EA, and low mindfulness appear to be significant correlates for anxiety-related symptoms in younger and older adults. © The Author(s) 2015.

ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1981-01-01

The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO study).

PubMed

Hagendorens, M M; Bridts, C H; Lauwers, K; van Nuijs, S; Ebo, D G; Vellinga, A; De Clerck, L S; Van Bever, H P; Weyler, J J; Stevens, W J

2005-06-01

To evaluate the influence of perinatal environmental factors on early sensitization, atopic dermatitis and wheezing during the first year. Information on pregnancy-related factors, parental atopic history, environmental factors and the clinical course of the infant until age one was gathered by questionnaires, as part of a prospective birth cohort study (Prospective study on the Influence of Perinatal factors on the Occurrence of asthma and allergies [PIPO-study]). Quantification of total and specific IgE was performed in 810 children and their parents. Early sensitization was found in 107/810 (13%) of the infants. Multiple regression analysis showed that specific IgE in fathers was a risk factor for early sensitization in their daughters (adjusted odds ratios (OR(adj)) 2.21 (95% confidence interval (CI) 1.10-4.49); P=0.03), whereas in boys, day care attendance was shown to be protective for early sensitization (OR(adj) 0.38 (95% CI 0.20-0.71); P=0.001). Atopic dermatitis occurred in 195/792 infants (25%). Specific IgE in the mother (OR(adj) 1.52 (95% CI 1.06-2.19); P=0.02) and in the infant (OR(adj) 4.20 (95% CI 2.63-6.68); P<0.001) were both risk factors for the occurence of atopic dermatitis, whereas postnatal exposure to cats was negatively associated with atopic dermatitis (OR(adj) 0.68 (0.47-0.97); P=0.03). Postnatal exposure to cigarette smoke (OR(adj) 3.31 (95% CI 1.79-6.09); P<0.001) and day care attendance (OR(adj) 1.96 (95% CI 1.18-3.23); P=0.009) were significantly associated with early wheezing, which occurred in 25% (197/795) of the infants. The effect of paternal sensitization and day care attendance on sensitization is gender dependent. Maternal sensitization predisposes for atopic dermatitis, whereas postnatal exposure to cats had a protective effect.

Factors Contributing to the Self-Reported Prevalence of Multiple Chemical Sensitivity in Public Facility Workers and the General Population of Korea.

PubMed

Heo, Yong; Kim, Sang-Hoon; Lee, Seok-Ki; Kim, Hyoung-Ah

Multiple chemical sensitivity (MCS), an acquired disorder with multiple recurrent symptoms, has been studied for its association with diverse environmental factors. The present study investigated the factors associated with the self-reported prevalence of MCS in public facility workers and the general population in Korea. The Quick Environmental Exposure Sensitivity Inventory (QEESI) questionnaire was obtained from public facility workers (N=530) and the general population (N=500) to determine the prevalence of MCS and the degree of its risk. Information about demographic characteristics, subjective perceptions of sick building syndrome or sick house syndrome or allergy (SBS/SHS/Allergy), and certain home- or workplace-related events were also obtained. There was not a statistical difference between the public facility workers and the general population in the QEESI scores. The overall prevalence of MCS was 14.4% and there was no statistical difference between the two groups. Regarding the overall degree of risk of MCS, 21.8% of the study subjects were categorized as "very suggestive", and there was no significant difference between the two groups. Gender and the subjective perception of SBS/SHS/Allergy significantly affected the prevalence of MCS and the MCS risk criteria. Considering the absence of diagnostic criteria and/or treatment methods for MCS in Korea, these results can be utilized in establishing future strategies to manage MCS.

Rainfall or parameter uncertainty? The power of sensitivity analysis on grouped factors

NASA Astrophysics Data System (ADS)

Nossent, Jiri; Pereira, Fernando; Bauwens, Willy

2017-04-01

Hydrological models are typically used to study and represent (a part of) the hydrological cycle. In general, the output of these models mostly depends on their input rainfall and parameter values. Both model parameters and input precipitation however, are characterized by uncertainties and, therefore, lead to uncertainty on the model output. Sensitivity analysis (SA) allows to assess and compare the importance of the different factors for this output uncertainty. Hereto, the rainfall uncertainty can be incorporated in the SA by representing it as a probabilistic multiplier. Such multiplier can be defined for the entire time series, or several of these factors can be determined for every recorded rainfall pulse or for hydrological independent storm events. As a consequence, the number of parameters included in the SA related to the rainfall uncertainty can be (much) lower or (much) higher than the number of model parameters. Although such analyses can yield interesting results, it remains challenging to determine which type of uncertainty will affect the model output most due to the different weight both types will have within the SA. In this study, we apply the variance based Sobol' sensitivity analysis method to two different hydrological simulators (NAM and HyMod) for four diverse watersheds. Besides the different number of model parameters (NAM: 11 parameters; HyMod: 5 parameters), the setup of our sensitivity and uncertainty analysis-combination is also varied by defining a variety of scenarios including diverse numbers of rainfall multipliers. To overcome the issue of the different number of factors and, thus, the different weights of the two types of uncertainty, we build on one of the advantageous properties of the Sobol' SA, i.e. treating grouped parameters as a single parameter. The latter results in a setup with a single factor for each uncertainty type and allows for a straightforward comparison of their importance. In general, the results show a clear

The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing.

PubMed

Kou, Xiaoxing; Xu, Xingtian; Chen, Chider; Sanmillan, Maria Laura; Cai, Tao; Zhou, Yanheng; Giraudo, Claudio; Le, Anh; Shi, Songtao

2018-03-14

Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs. Moreover, we reveal that MSCs produce and secrete interleukin-1 receptor antagonist (IL-1RA) associated with sEVs to maintain rapid wound healing in the gingiva via the Fas/Fap-1/Cav-1 cascade. Tumor necrosis factor-α (TNF-α) serves as an activator to up-regulate Fas and Fap-1 expression via the nuclear factor κB pathway to promote IL-1RA release. This study identifies a previously unknown Fas/Fap-1/Cav-1 axis that regulates SNARE-mediated sEV and IL-1RA secretion in stem cells, which contributes to accelerated wound healing. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

NASA Technical Reports Server (NTRS)

Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

2012-01-01

We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.

PubMed

Vo, Ashley A; Sinha, Aditi; Haas, Mark; Choi, Jua; Mirocha, James; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Jordan, Stanley C

2015-07-01

Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern. Between July 2006 and December 2012, 226 highly sensitized patients received transplants after desensitization. Most received alemtuzumab induction and standard immunosuppression. Two groups were examined: ABMR (n = 181) and ABMR (n = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed. Significant risks for ABMR included previous transplants and pregnancies as sensitizing events, donor-specific antibody (DSA) relative intensity scores greater than 17, presence of both class I and II DSAs at transplant and time on waitlist. The ABMR showed a significant benefit for graft survival and glomerular filtration rate at 5 years (P < 0.0001). Banff pathology characteristics for ABMR patients with or without graft loss did not differ. C4d versus C4d ABMR did not predict graft loss (P = 0.086). Thrombotic microangiopathy (TMA) significantly predicted graft failure (P = 0.045). The ABMR episodes were treated with I+R (n = 25), or, in more severe ABMR, plasma exchange (PLEX)+I+R (n = 20). Graft survival for patients treated with I+R was superior (P = 0.028). Increased mortality was seen in ABMR patients experiencing graft loss after ABMR treatment (P = 0.004). The PLEX + Eculizumab improved graft survival for TMA patients (P = 0.036). Patients desensitized with I+R who remain ABMR have long-term graft and patient survival. The ABMR patients have significantly reduced graft survival and glomerular filtration rate at 5 years, especially TMA. Severe ABMR episodes benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance and reduction strategies before transplantation are critical to avoiding ABMR and improving long-term outcomes.

A simple and sensitive quantitation of N,N-dimethyltryptamine by gas chromatography with surface ionization detection.

PubMed

Ishii, A; Seno, H; Suzuki, O; Hattori, H; Kumazawa, T

1997-01-01

A simple and sensitive method for determination of N,N-dimethyltryptamine (DMT) by gas chromatography (GC) with surface ionization detection (SID) is presented. Whole blood or urine, containing DMT and gramine (internal standard), was subjected to solid-phase extraction with a Sep-Pak C18 cartridge before analysis by GC-SID. The calibration curve was linear in the DMT range of 1.25-20 ng/mL blood or urine. The detection limit of DMT was about 0.5 ng/mL (10 pg on-column). The recovery of both DMT and gramine spiked in biological fluids was above 86%.

Increased sensitivity of spin noise spectroscopy using homodyne detection in n -doped GaAs

NASA Astrophysics Data System (ADS)

Petrov, M. Yu.; Kamenskii, A. N.; Zapasskii, V. S.; Bayer, M.; Greilich, A.

2018-03-01

We implement the homodyne detection scheme for an increase in the polarimetric sensitivity in spin noise spectroscopy. Controlling the laser intensity of the local oscillator, which is guided around the sample and does not perturb the measured spin system, we are able to improve the signal-to-noise ratio. The opportunity for additional amplification of the measured signal strength allows us to reduce the probe laser intensity incident on the sample and therefore to approach the nonperturbative regime. The efficiency of this scheme with signal enhancement by more than a factor of 3 at low probe powers is demonstrated on bulk n -doped GaAs, where the reduced electron-spin relaxation rate is shown experimentally. Additionally, the control of the optical phase provides us with the possibility to switch between measuring Faraday rotation and ellipticity without changes in the optical setup.

Study of Pre-disposing Factors of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Antibiotic Prescribing Pattern with Reference to Antibiotic Sensitivity Test.

PubMed

Shrestha, R; Shrestha, B; Shakya Shrestha, S; Pant, A; Prajapati, B; Karmacharya, B M

2015-01-01

Background Chronic Obstructive Pulmonary Disease (COPD) affects about 329 million people worldwide, which is nearly 5% of the entire global population. In the context of Nepal, COPD accounts for 43% of the non-communicable disease burden and 2.56% of hospitalizations. Various pre-disposing factors like bacterial, viral, fungal, smoking, occupational exposures and genetic factors have been proposed to precipitate COPD and its exacerbation though, the definitive pre-disposing factors and factors related to acute exacerbation have not been determined in the context of Nepal. Objective To find out the pre-disposing factors and the related causative agents for COPD. Method A cross sectional study was conducted in a tertiary care hospital. Patients of all age group who were diagnosed as COPD and admitted in the hospital were included in this study. Patients were interviewed using structured questionnaire. The sociodemographic data including personal and medical history were recorded from those participants. In addition, sputum from those patients was sent for culture to investigate the possible responsible pathogens as well as its antibiotic sensitivity pattern. Result A total of 150 patients having Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) who have admitted from either emergency or out-patient department of the hospital were included in this study. Among the total number of patients, more than half of them were female (n=82). In addition, analysis of occupations shows that most of them were either farmer (36.0%) or housewife (30.7%). In total studied patients (n=150), most of them were using traditional firewood (83%) for cooking purpose and majority of patients (91%) were smokers. Most of the sputum samples show growth of gram-positive cocci (26.7%) and gram negative bacilli (27.5%). Considering the overall sensitivity pattern, the higher sensitivity was recorded for Co-trimoxazole and Ciprofloxacin while higher rate of resistance was noted

Identification of the protein responsible for pyruvate transport into rat liver and heart mitochondria by specific labelling with [3H]N-phenylmaleimide.

PubMed

Thomas, A P; Halestrap, A P

1981-05-15

1. N-Phenylmaleimide irreversibly inhibits pyruvate transport into rat heart and liver mitochondria to a much greater extent than does N-ethylmaleimide, iodoacetate or bromopyruvate. alpha-Cyanocinnamate protects the pyruvate transporter from attack by this thiol-blocking reagent. 2. In both heart and liver mitochondria alpha-cyanocinnamate diminishes labelling by [3H]N-phenylmaleimide of a membrane protein of subunit mol.wt. 15000 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 3. Exposure of mitochondrial to unlabelled N-phenylmaleimide in the presence of alpha-cyanocinnamate, followed by removal of alpha-cyanocinnamate and exposure to [3H]N-phenylmaleimide, produced specific labelling of the same protein. 4. Both labelling and kinetic experiments with inhibitors gave values for the approximate amount of carrier present in liver and heart mitochondria of 100 and 450 pmol/mg of mitochondrial protein respectively. 5. The turnover numbers for net pyruvate transport and pyruvate exchange at 0 degrees C were 6 and 200 min-1 respectively.

N-bromosuccinimide-fluorescein based sensitive flow-injection chemiluminescence determination of phenformin.

PubMed

Wang, Zhouping; Zhang, Zhujun; Fu, Zhifeng; Fang, Luqiu; Zhang, Xiao

2004-02-01

A novel and highly sensitive method for the determination of phenformin over the range of 6 x 10(-9) - 1 x 10(-5) g ml(-1) in pharmaceutical formulations with flow-injection chemiluminescence (CL) detection is proposed. The method is based on the CL produced during the oxidation of N-bromosuccinimide (NBS) in an alkaline medium in the presence of fluorescein as an effective energy transfer agent. The use of cetyltrimethylammonium bromide (CTAB) as a sensitizer enhances the signal magnitude by about 100 times. The detection limit is 2 x 10(-9) g ml(-1) (3sigma) with a relative standard deviation of 2.3% (n = 11) at 1 x 10(-7) g ml(-1) phenformin. Ninety samples can be determined per hour. The method was evaluated by carrying out a recovery study and by the analysis of commercial formulations. The obtained results compared well with those by an official method, and demonstrated good accuracy and precision. The possible CL mechanism of the proposed system was also briefly analyzed.

Vesicle Adhesion and Fusion Studied by Small-Angle X-Ray Scattering.

PubMed

Komorowski, Karlo; Salditt, Annalena; Xu, Yihui; Yavuz, Halenur; Brennich, Martha; Jahn, Reinhard; Salditt, Tim

2018-04-24

We have studied the adhesion state (also denoted by docking state) of lipid vesicles as induced by the divalent ions Ca 2+ or Mg 2+ at well-controlled ion concentration, lipid composition, and charge density. The bilayer structure and the interbilayer distance in the docking state were analyzed by small-angle x-ray scattering. A strong adhesion state was observed for DOPC:DOPS vesicles, indicating like-charge attraction resulting from ion correlations. The observed interbilayer separations of ∼1.6 nm agree quantitatively with the predictions of electrostatics in the strong coupling regime. Although this phenomenon was observed when mixing anionic and zwitterionic (or neutral) lipids, pure anionic membranes (DOPS) with highest charge density σ resulted in a direct phase transition to a multilamellar state, which must be accompanied by rupture and fusion of vesicles. To extend the structural assay toward protein-controlled docking and fusion, we have characterized reconstituted N-ethylmaleimide-sensitive factor attachment protein receptors in controlled proteoliposome suspensions by small-angle x-ray scattering. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Regulation of exocytosis by the exocyst subunit Sec6 and the SM protein Sec1.

PubMed

Morgera, Francesca; Sallah, Margaret R; Dubuke, Michelle L; Gandhi, Pallavi; Brewer, Daniel N; Carr, Chavela M; Munson, Mary

2012-01-01

Trafficking of protein and lipid cargo through the secretory pathway in eukaryotic cells is mediated by membrane-bound vesicles. Secretory vesicle targeting and fusion require a conserved multisubunit protein complex termed the exocyst, which has been implicated in specific tethering of vesicles to sites of polarized exocytosis. The exocyst is directly involved in regulating soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) complexes and membrane fusion through interactions between the Sec6 subunit and the plasma membrane SNARE protein Sec9. Here we show another facet of Sec6 function-it directly binds Sec1, another SNARE regulator, but of the Sec1/Munc18 family. The Sec6-Sec1 interaction is exclusive of Sec6-Sec9 but compatible with Sec6-exocyst assembly. In contrast, the Sec6-exocyst interaction is incompatible with Sec6-Sec9. Therefore, upon vesicle arrival, Sec6 is proposed to release Sec9 in favor of Sec6-exocyst assembly and to simultaneously recruit Sec1 to sites of secretion for coordinated SNARE complex formation and membrane fusion.

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

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

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

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

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. The tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE PAGES

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.; ...

2017-08-16

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking

PubMed Central

Iwakiri, Yasuko; Satoh, Ayano; Chatterjee, Suvro; Toomre, Derek K.; Chalouni, Cecile M.; Fulton, David; Groszmann, Roberto J.; Shah, Vijay H.; Sessa, William C.

2006-01-01

Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of N-ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes. PMID:17170139

A multivariate relationship for the impact sensitivities of energetic N-nitrocompounds based on bond dissociation energy.

PubMed

Li, Jinshan

2010-02-15

The ZPE-corrected N-NO(2) bond dissociation energies (BDEs(ZPE)) of a series of model N-nitrocompounds and typical energetic N-nitrocompounds have been calculated using density functional theory methods. Computed results show that using the 6-31G** basis set the UB3LYP calculated BDE(ZPE) is similar to the B3PW91 but is less than the UB3P86 and that for both UB3P86 and UB3PW91 methods the 6-31G(**) calculated BDE(ZPE) is close to the 6-31++G(**). For the series of model N-nitrocompounds it is drawn from the NBO analysis that at the UB3LYP/6-31G(**) level the order of BDE(ZPE) is not only in line with that of bond order but also with that of the energy gap between N-NO(2) bond and antibond orbitals. For the typical energetic N-nitrocompounds the impact sensitivity is strongly related to the BDE(ZPE) indeed, and based on the BDEs(ZPE) calculated at different density functional theory levels this work has established a good multivariate correlation of impact sensitivity with molecular parameters, which provides a method to address the sensitivity problem.

Taxometric and Factor Analytic Models of Anxiety Sensitivity among Youth: Exploring the Latent Structure of Anxiety Psychopathology Vulnerability

ERIC Educational Resources Information Center

Bernstein, Amit; Zvolensky, Michael J.; Stewart, Sherry; Comeau, Nancy

2007-01-01

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), a well-established affect-sensitivity individual difference factor, among youth by employing taxometric and factor analytic approaches in an integrative manner. Taxometric analyses indicated that AS, as indexed by the Child Anxiety Sensitivity…

S-Glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans

PubMed Central

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-01-01

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10µCa2+½ at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mm) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnIf) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnIf were blocked by N-ethylmaleimide (NEM). S-Nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnIf. In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnIf. When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnIf, DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S

S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans.

PubMed

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-03-15

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10 [Ca2+] at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mM) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnI(f)) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnI(f) were blocked by N-ethylmaleimide (NEM). S-nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnI(f). In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnI(f). When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnI(f), DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S

Visible-light sensitization of TiO2 photocatalysts via wet chemical N-doping for the degradation of dissolved organic compounds in wastewater treatment: a review

NASA Astrophysics Data System (ADS)

Zhang, Wei; Jia, Baoping; Wang, Qiuze; Dionysiou, Dionysois

2015-05-01

Increased pollution of ground and surface water and emerging new micropollutants from a wide variety of industrial, municipal, and agricultural sources has increased demand on the development of innovative new technologies and materials whereby challenges associated with the provision of safe potable water can be addressed. Heterogeneous photocatalysis using visible-light sensitized TiO2 photocatalysts has attracted a lot of attention as it can effectively remove dissolved organic compound in water without generating harmful by-products. On this note, recent progress on visible-light sensitive TiO2 synthesis via wet chemical N-doping method is reviewed. In a typical visible-light sensitive TiO2 preparation via wet chemical methods, the chemical (e.g., N-doping content and states) and morphological properties (e.g., particle size, surface area, and crystal phase) of TiO2 in as-prepared resultants are sensitively dependent on many experimental variables during the synthesis. This has also made it very difficult to provide a universal guidance at this stage with a certainty for each variable of N-doping preparation. Instead of one-factor-at-a-time style investigation, a statistically valid parameter optimization investigation for general optima of photocatalytic activity will be certainly useful. Optimization of the preparation technique is envisaged to be beneficial to many environmental applications, i.e., dissolved organic compounds removal in wastewater treatment.

Sensitivity of terrestrial N2O emission to atmospheric nitrogen deposition

NASA Astrophysics Data System (ADS)

Ito, A.; Sudo, K.; Nishina, K.; Ishijima, K.; Inatomi, M. I.

2015-12-01

Terrestrial N2O emission is generated from several nitrogen sources including biological fixation, agricultural fertilizer, and atmospheric deposition. There remain large uncertainties how much N2O is produced from atmospheric deposition. This is a crosscutting issue between global warming and atmospheric pollution. In this study, we assessed the sensitivity of global terrestrial N2O emission to atmospheric deposition, using a process-based model VISIT. In the model, N2O emission is estimated separately for nitrification and denitrfication with the NGAS parameterization. The global simulations were conducted from 1901 to 2014 at spatial resolution of 0.5 degree. Atmospheric deposition of ammonium, NOy, and organic nitrogen simulated by the atmospheric chemistry model CHASER from the pre-industrial time to the present was used. Annual total nitrogen deposition was estimated to increase from 27 Tg N in 1901 to 77 Tg N in 2014. The total N2O emission was also estimated to increase in the period, but it was largely attributable to the increased emission from croplands. We need further investigations for the N2O emission from natural soils, which may be nitrogen-limited.

Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the Ascomycete Sordaria macrospora.

PubMed

Traeger, Stefanie; Nowrousian, Minou

2015-04-14

During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. Copyright © 2015 Traeger and Nowrousian.

Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the Ascomycete Sordaria macrospora

PubMed Central

Traeger, Stefanie; Nowrousian, Minou

2015-01-01

During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. PMID:25873638

Rolling blackout is required for synaptic vesicle exocytosis.

PubMed

Huang, Fu-De; Woodruff, Elvin; Mohrmann, Ralf; Broadie, Kendal

2006-03-01

Rolling blackout (RBO) is a putative transmembrane lipase required for phospholipase C-dependent phosphatidylinositol 4,5-bisphosphate-diacylglycerol signaling in Drosophila neurons. Conditional temperature-sensitive (TS) rbo mutants display complete, reversible paralysis within minutes, demonstrating that RBO is acutely required for movement. RBO protein is localized predominantly in presynaptic boutons at neuromuscular junction (NMJ) synapses and throughout central synaptic neuropil, and rbo TS mutants display a complete, reversible block of both central and peripheral synaptic transmission within minutes. This phenotype appears limited to adults, because larval NMJs do not manifest the acute blockade. Electron microscopy of adult rbo TS mutant boutons reveals an increase in total synaptic vesicle (SV) content, with a concomitant shrinkage of presynaptic bouton size and an accumulation of docked SVs at presynaptic active zones within minutes. Genetic tests reveal a synergistic interaction between rbo and syntaxin1A TS mutants, suggesting that RBO is required in the mechanism of N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated SV exocytosis, or in a parallel pathway necessary for SV fusion. The rbo TS mutation does not detectably alter SNARE complex assembly, suggesting a downstream requirement in SV fusion. We conclude that RBO plays an essential role in neurotransmitter release, downstream of SV docking, likely mediating SV fusion.

[Study on the current situation and influential factors of anxiety sensitivity among middle school students in Chongqing].

PubMed

Li, Qian-Qian; Zhang, Da-Jun; Guo, Lan-Ting; Feng, Zheng-Zhi; Wu, Ming-Xia

2007-09-01

To explore the status and influencing factors on anxiety sensitivity among middle school students in Chongqing. 58 classes from 12 schools were randomly selected in four administrative districts of Chongqing city. A total number of 2700 students was included for final analysis including 48.5% from junior high school and 51.5% from senior high school students with 49.2% boys and 50.8% girls. The Chinese version of the Anxiety Sensitivity Index-Revision, Adolescent Self-Rating Life Events Check List (ASLEC) and State-Trait Anxiety Inventory (STAI) were used. (1) There was no significant difference between grade groups (P = 0.49). (2) The level of girl's anxiety sensitivity was always higher than boy's (P < 0.001). (3) Data from multiple linear regression showed that the influential factors to the degree of anxiety sensitivity were: state of anxiety, trait anxiety, life events, sex, stress from learning, etc (standard coefficients of regression were 0.258, 0.163, 0.112, 0.093, 0.124, -0.096, 0.096). The major influential factors of anxiety sensitivity would include: sex, stress from learning, life events, interpersonal relationship, state of anxiety and trait anxiety.

Adult Attachment States of Mind: Measurement Invariance across Ethnicity and Associations with Maternal Sensitivity

PubMed Central

Haltigan, John D.; Leerkes, Esther M.; Wong, Maria S.; Fortuna, Keren; Roisman, Glenn I.; Supple, Andrew J.; O’Brien, Marion; Calkins, Susan D.; Plamondon, André

2017-01-01

The current study examined the developmental significance of mothers’ adult attachment representations assessed prenatally with the Adult Attachment Interview in relation to observed maternal sensitivity at 6 months postpartum in an ethnically diverse sample (N = 131 African American; N = 128 European American). Multiple groups confirmatory factor analyses provided evidence for partial measurement invariance of a two factor dismissing and preoccupied latent structure of adult attachment across the two ethnic groups of women. African American women showed modest elevations on the preoccupied factor relative to European American women. Although the dismissing factor showed an empirically equivalent negative association with maternal sensitivity in both ethnic groups, this effect was reduced to marginal significance when controlling for maternal socioeconomic status. PMID:24936609

Nerve Growth Factor Sensitizes Adult Sympathetic Neurons to the Proinflammatory Peptide Bradykinin

PubMed Central

Vivas, Oscar; Kruse, Martin

2014-01-01

Levels of nerve growth factor (NGF) are elevated in inflamed tissues. In sensory neurons, increases in NGF augment neuronal sensitivity (sensitization) to noxious stimuli. Here, we hypothesized that NGF also sensitizes sympathetic neurons to proinflammatory stimuli. We cultured superior cervical ganglion (SCG) neurons from adult male Sprague Dawley rats with or without added NGF and compared their responsiveness to bradykinin, a proinflammatory peptide. The NGF-cultured neurons exhibited significant depolarization, bursts of action potentials, and Ca2+ elevations after bradykinin application, whereas neurons cultured without NGF showed only slight changes in membrane potential and cytoplasmic Ca2+ levels. The NGF effect, which requires trkA receptors, takes hours to develop and days to reverse. We addressed the ionic mechanisms underlying this sensitization. NGF did not alter bradykinin-induced M-current inhibition or phosphatidylinositol 4,5-bisphosphate hydrolysis. Maxi-K channel-mediated current evoked by depolarizations was reduced by 50% by culturing neurons in NGF. Application of iberiotoxin or paxilline, blockers of Maxi-K channels, mimicked NGF treatment and sensitized neurons to bradykinin application. A calcium channel blocker also mimicked NGF treatment. We found that NGF reduces Maxi-K channel opening by decreasing the activity of nifedipine-sensitive calcium channels. In conclusion, culture in NGF reduces the activity of L-type calcium channels, and secondarily, the calcium-sensitive activity of Maxi-K channels, rendering sympathetic neurons electrically hyper-responsive to bradykinin. PMID:25186743

Targeting miR-381-NEFL axis sensitizes glioblastoma cells to temozolomide by regulating stemness factors and multidrug resistance factors.

PubMed

Wang, Zeyou; Yang, Jing; Xu, Gang; Wang, Wei; Liu, Changhong; Yang, Honghui; Yu, Zhibin; Lei, Qianqian; Xiao, Lan; Xiong, Jing; Zeng, Liang; Xiang, Juanjuan; Ma, Jian; Li, Guiyuan; Wu, Minghua

2015-02-20

MicroRNA-381 (miR-381) is a highly expressed onco-miRNA that is involved in malignant progression and has been suggested to be a good target for glioblastoma multiforme (GBM) therapy. In this study, we employed two-dimensional fluorescence differential gel electrophoresis (2-D DIGE) and MALDI-TOF/TOF-MS/MS to identify 27 differentially expressed proteins, including the significantly upregulated neurofilament light polypeptide (NEFL), in glioblastoma cells in which miR-381 expression was inhibited. We identified NEFL as a novel target molecule of miR-381 and a tumor suppressor gene. In human astrocytoma clinical specimens, NEFL was downregulated with increased levels of miR-381 expression. Either suppressing miR-381 or enforcing NEFL expression dramatically sensitized glioblastoma cells to temozolomide (TMZ), a promising chemotherapeutic agent for treating GBMs. The mechanism by which these cells were sensitized to TMZ was investigated by inhibiting various multidrug resistance factors (ABCG2, ABCC3, and ABCC5) and stemness factors (ALDH1, CD44, CKIT, KLF4, Nanog, Nestin, and SOX2). Our results further demonstrated that miR-381 overexpression reversed the viability of U251 cells exhibiting NEFL-mediated TMZ sensitivity. In addition, NEFL-siRNA also reversed the proliferation rate of U251 cells exhibiting locked nucleic acid (LNA)-anti-miR-381-mediated TMZ sensitivity. Overall, the miR-381-NEFL axis is important for TMZ resistance in GBM and may potentially serve as a novel therapeutic target for glioma.

Sensitivity of the diagnostic radiological index of protection to procedural factors in fluoroscopy.

PubMed

Jones, A Kyle; Pasciak, Alexander S; Wagner, Louis K

2016-07-01

To evaluate the sensitivity of the diagnostic radiological index of protection (DRIP), used to quantify the protective value of radioprotective garments, to procedural factors in fluoroscopy in an effort to determine an appropriate set of scatter-mimicking primary beams to be used in measuring the DRIP. Monte Carlo simulations were performed to determine the shape of the scattered x-ray spectra incident on the operator in different clinical fluoroscopy scenarios, including interventional radiology and interventional cardiology (IC). Two clinical simulations studied the sensitivity of the scattered spectrum to gantry angle and patient size, while technical factors were varied according to measured automatic dose rate control (ADRC) data. Factorial simulations studied the sensitivity of the scattered spectrum to gantry angle, field of view, patient size, and beam quality for constant technical factors. Average energy (Eavg) was the figure of merit used to condense fluence in each energy bin to a single numerical index. Beam quality had the strongest influence on the scattered spectrum in fluoroscopy. Many procedural factors affect the scattered spectrum indirectly through their effect on primary beam quality through ADRC, e.g., gantry angle and patient size. Lateral C-arm rotation, common in IC, increased the energy of the scattered spectrum, regardless of the direction of rotation. The effect of patient size on scattered radiation depended on ADRC characteristics, patient size, and procedure type. The scattered spectrum striking the operator in fluoroscopy is most strongly influenced by primary beam quality, particularly kV. Use cases for protective garments should be classified by typical procedural primary beam qualities, which are governed by the ADRC according to the impacts of patient size, anatomical location, and gantry angle.

In vitro cytotoxicity and differential cellular sensitivity of derivatives of diamino acids. II. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl nitrosoureas.

PubMed

Dulude, H; Salvador, R; Gallant, G

1995-01-01

The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl nitrosourea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. The compounds tested showed an in vitro anticancer activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU, chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the nitrosoureas seems to play a role in the general selectivity of our compounds. The N1-methyl and N1-2-chloroethyl nitrosourea derivatives are more selective for central nervous system cell lines, the N1-allyl nitrosourea derivatives are more selective for lung cancer cell lines and the N1-propargyl nitrosoureas are more selective for leukemia cell lines.

Influence of surface oxides on hydrogen-sensitive Pd:GaN Schottky diodes

NASA Astrophysics Data System (ADS)

Weidemann, O.; Hermann, M.; Steinhoff, G.; Wingbrant, H.; Lloyd Spetz, A.; Stutzmann, M.; Eickhoff, M.

2003-07-01

The hydrogen response of Pd:GaN Schottky diodes, prepared by in situ and ex situ deposition of catalytic Pd Schottky contacts on Si-doped GaN layers is compared. Ex situ fabricated devices show a sensitivity towards molecular hydrogen, which is about 50 times higher than for in situ deposited diodes. From the analysis of these results, we conclude that adsorption sites for atomic hydrogen in Pd:GaN sensors are provided by an oxidic intermediate layer. In addition, in situ deposited Pd Schottky contacts reveal lower barrier heights and drastically higher reverse currents. We suggest that the passivation of the GaN surface before ex situ deposition of Pd also results in quenching of leakage paths caused by structural defects.

Factors affecting the sensitivity and specificity of the Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs.

PubMed

Saarela, Ville; Falck, Aura; Airaksinen, P Juhani; Tuulonen, Anja

2012-03-01

To evaluate the factors affecting the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to glaucomatous progression in stereoscopic ONH photographs. The factors affecting the sensitivity and specificity of the vertical cup : disc ratio, the cup : disc area ratio, the cup volume, the rim area and a linear discriminant function to progression were analysed. These parameters were the best indicators of progression in a retrospective study of 476 eyes. The reference standard for progression was the masked evaluation of stereoscopic ONH photographs. The factors having the most significant effect on the sensitivity and specificity of the stereometric ONH parameters were the reference height difference and the mean topography standard deviation (TSD), indicating image quality. Also, the change in the TSD and age showed consistent, but variably significant, influence on all parameters tested. The sensitivity and specificity improved when there was little change in the reference height, the image quality was good and stable, and the patients were younger. The sensitivity and specificity of the vertical cup : disc ratio was improved by a large disc area and high baseline cup : disc area ratio. The rim area showed a better sensitivity and specificity for progression with a small disc area and low baseline cup : disc area ratio. The factors affecting the sensitivity and specificity of the stereometric ONH parameters to glaucomatous progression in disc photographs are essentially the same as those affecting the measurement variability of the HRT. © 2010 The Authors. Acta Ophthalmologica © 2010 Acta Ophthalmologica Scandinavica Foundation.

Induction of glandular stomach cancers in Helicobacter pylori-sensitive Mongolian gerbils treated with N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine in drinking water.

PubMed

Tatematsu, M; Yamamoto, M; Shimizu, N; Yoshikawa, A; Fukami, H; Kaminishi, M; Oohara, T; Sugiyama, A; Ikeno, T

1998-02-01

An animal model of stomach carcinogenesis was established using Mongolian gerbils with N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as the carcinogens. In addition, the sensitivity of these gerbils to Helicobacter pylori (H. pylori) was confirmed. One hundred and sixty specific pathogen-free male MGS/Sea animals, 7 weeks old, were treated with MNU in the drinking water (30 ppm for alternate weeks to give 10 weeks exposure, or 10 ppm or 3 ppm for 20 weeks continuous exposure), or given MNNG in the drinking water at 400 ppm or 200 ppm for 20 weeks, or orally inoculated with ATCC43504 H. pylori (1.7 x 10(8) CFUs/animal). Adenocarcinomas in the glandular stomach were found in 2 out of 12 effective animals (2/ 12) treated with 30 ppm MNU at week 20, although all were dead or moribund by week 30 due to MNU toxicity. At week 50, the incidences of gastric adenocarcinomas in groups treated with 10 ppm MNU, 3 ppm MNU, 400 ppm MNNG, and 200 ppm MNNG were 2/21 (9.5%), 1/23 (4.3%), 7/ 11 (63.6%), and 1/10 (10.0%). The lesions were generally well differentiated, although poorly differentiated adenocarcinoma was also found in a single gerbil in each of the 10 ppm MNU and 400 ppm MNNG groups. In control animals no tumors were found. In the infection study, the animals were killed at week 20, and H. pylori was detected in all cases, causing multiple erosions with marked inflammatory cell infiltration in the lamina propria and submucosa, and frequent formation of lymphoid follicles. Thus, MNU and MNNG in the drinking water induced neoplastic lesions in the glandular stomach epithelium of H. pylori-sensitive gerbils.

Perceptual load manipulation reveals sensitivity of the face-selective N170 to attention.

PubMed

Mohamed, Tarik N; Neumann, Markus F; Schweinberger, Stefan R

2009-05-27

It has been controversial whether the face-sensitive N170 is affected by selective attention. We manipulated attention sensu Lavie's perceptual load theory to short (200 ms) presentations of task-irrelevant unfamiliar faces or houses, while participants identified superimposed target letters 'X' versus 'N'. These targets were strings of either six identical (low load) or six different letters (high load). Under low load, we found a prominent face-selective N170 response. Under high load, however, we not only observed a dramatic reduction of the face N170 but also an unexpected enhancement of the house N170, such that face selectivity was almost completely lost. We conclude that the early stages of face processing indexed by the N170 strongly depend on selective attention.

On the differentiation of N2 components in an appetitive choice task: evidence for the revised Reinforcement Sensitivity Theory.

PubMed

Leue, Anja; Chavanon, Mira-Lynn; Wacker, Jan; Stemmler, Gerhard

2009-11-01

Task- and personality-related modulations of the N2 were probed within the framework of the revised Reinforcement Sensitivity Theory (RST). Using an appetitive choice task, we investigated 58 students with extreme scores on the behavioral inhibition system and behavioral approach system (BIS/BAS) scales. The baseline-to-peak N2 amplitude was sensitive to the strength of decision conflict and demonstrated RST-related personality differences. In addition to the baseline N2 amplitude, temporal PCA results suggested two N2 components accounting for a laterality effect and capturing different N2 patterns for BIS/BAS groups with increasing conflict level. Evidence for RST-related personality differences was obtained for baseline-to-peak N2 and tPCA components in the present task. The results support the RST prediction that BAS sensitivity modulates conflict processing and confirm the cognitive-motivational conflict concept of RST.

The effects of insulin sensitizers on the cardiovascular risk factors in women with polycystic ovary syndrome.

PubMed

Kassi, E; Diamanti-Kandarakis, E

2008-12-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in pre-menopausal women characterized by menstrual cycle disturbances, chronic anovulation, and clinical and/or biochemical hyperandrogenism. Although, the primary etiology of PCOS remains unknown, insulin resistance/hyperinsulinemia plays a pivotal role in the pathogenesis of the syndrome. A growing body of recent data support that women with PCOS have displayed an increased prevelance of cardiovascular disease (CVD) risk factors putting potentially at a hight risk for heart disease. Most of these CVD risk factors are etiologically correlated with insulin resistance/hyperinsulinemia, highlighting the role of insulin sensitizers in the therapeutic quiver for the chronic treatment of PCOS. In this review, we discuss the current literature on the CVD risk factors in PCOS and the influence of insulin sensitizers upon these risk factors.

Proposal to search for mu- N -> e- N with a single event sensitivity below 10 -16

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

Carey, R.M.; Lynch, K.R.; Miller, J.P.

2008-10-01

We propose a new experiment, Mu2e, to search for charged lepton flavor violation with unprecedented sensitivity. We will measure the ratio of the coherent neutrinoless conversion in the field of a nucleus of a negatively charged muon into an electron to the muon capture process: R{sub {mu}e} = {mu}{sup -} + A(Z,N) {yields} e{sup -} + A(Z,N)/{mu}{sup -} + A(Z,N) {yields} {nu}{sub {mu}} + A(Z-1, N), with a sensitivity R{sub {mu}e} {le} 6 x 10{sup -17} at 90% CL. This is almost a four order-of-magnitude improvement over the existing limit. The observation of such a process would be unambiguous evidencemore » of physics beyond the Standard Model. Since the discovery of the muon in 1936, physicists have attempted to answer I.I. Rabi's famous question: 'Who ordered that?' Why is there a muon? What role does it play in the larger questions of why there are three families and flavors of quarks, leptons, and neutrinos? We know quarks mix through a mechanism described by the Cabbibo-Kobayashi-Maskawa matrix, which has been studied for forty years. Neutrino mixing has been observed in the last decade, but mixing among the family of charged leptons has never been seen. The current limits are of order 10{sup -11} - 10{sup -13} so the process is rare indeed. Why is such an experiment important and timely? A major motivation for experiments at the Large Hadron Collider (LHC) is the possible observation of supersymmetric particles in the TeV mass range. Many of these supersymmetric models predict a {mu}-e conversion signal at R{sub {mu}e} {approx} 10{sup -15}. We propose to search for {mu}-e conversion at a sensitivity that exceeds this by more than an order of magnitude. The LHC may not be able to conclusively distinguish among supersymmetric models, so Mu2e will provide invaluable information should the LHC observe a signal. In the case where the LHC finds no evidence of supersymmetry, or other beyond-the-standard-model physics, Mu2e will probe for new physics at mass scales

Comparative sensitizing potencies of fragrances, preservatives, and hair dyes.

PubMed

Lidén, Carola; Yazar, Kerem; Johansen, Jeanne D; Karlberg, Ann-Therese; Uter, Wolfgang; White, Ian R

2016-11-01

The local lymph node assay (LLNA) is used for assessing sensitizing potential in hazard identification and risk assessment for regulatory purposes. Sensitizing potency on the basis of the LLNA is categorized into extreme (EC3 value of ≤0.2%), strong (>0.2% to ≤2%), and moderate (>2%). To compare the sensitizing potencies of fragrance substances, preservatives, and hair dye substances, which are skin sensitizers that frequently come into contact with the skin of consumers and workers, LLNA results and EC3 values for 72 fragrance substances, 25 preservatives and 107 hair dye substances were obtained from two published compilations of LLNA data and opinions by the Scientific Committee on Consumer Safety and its predecessors. The median EC3 values of fragrances (n = 61), preservatives (n = 19) and hair dyes (n = 59) were 5.9%, 0.9%, and 1.3%, respectively. The majority of sensitizing preservatives and hair dyes are thus strong or extreme sensitizers (EC3 value of ≤2%), and fragrances are mostly moderate sensitizers. Although fragrances are typically moderate sensitizers, they are among the most frequent causes of contact allergy. This indicates that factors other than potency need to be addressed more rigorously in risk assessment and risk management. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stressful Life Events, Anxiety Sensitivity, and Internalizing Symptoms in Adolescents

PubMed Central

McLaughlin, Katie A.; Hatzenbuehler, Mark L.

2010-01-01

Anxiety sensitivity represents a robust risk factor for the development of anxiety symptoms among both adolescents and adults. However, the development of anxiety sensitivity among adolescents remains inadequately understood. In this study, the authors examined the role of stressful life events as a risk factor for the development of elevated anxiety sensitivity. Anxiety sensitivity was then examined in a longitudinal design as a mechanism linking stressful life events to changes in anxiety symptoms. Stressful life events, anxiety sensitivity, and internalizing symptoms were assessed in a diverse community sample of adolescents (N = 1,065) at 3 time points spanning 7 months. The results indicated that stressful life events were longitudinally associated with increases in anxiety sensitivity and that certain types of stressful life events, specifically events related to health and events related to family discord, were differentially predictive of increases in anxiety sensitivity. Moreover, anxiety sensitivity mediated the longitudinal relation between stressful life events and anxiety symptoms. Evidence was also found for the predictive specificity of anxiety sensitivity to symptoms of anxiety but not depression. PMID:19685962

Stressful life events, anxiety sensitivity, and internalizing symptoms in adolescents.

PubMed

McLaughlin, Katie A; Hatzenbuehler, Mark L

2009-08-01

Anxiety sensitivity represents a robust risk factor for the development of anxiety symptoms among both adolescents and adults. However, the development of anxiety sensitivity among adolescents remains inadequately understood. In this study, the authors examined the role of stressful life events as a risk factor for the development of elevated anxiety sensitivity. Anxiety sensitivity was then examined in a longitudinal design as a mechanism linking stressful life events to changes in anxiety symptoms. Stressful life events, anxiety sensitivity, and internalizing symptoms were assessed in a diverse community sample of adolescents (N = 1,065) at 3 time points spanning 7 months. The results indicated that stressful life events were longitudinally associated with increases in anxiety sensitivity and that certain types of stressful life events, specifically events related to health and events related to family discord, were differentially predictive of increases in anxiety sensitivity. Moreover, anxiety sensitivity mediated the longitudinal relation between stressful life events and anxiety symptoms. Evidence was also found for the predictive specificity of anxiety sensitivity to symptoms of anxiety but not depression.

Investigation of high sensitivity radio-frequency readout circuit based on AlGaN/GaN high electron mobility transistor

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Yu; Tan, Ren-Bing; Sun, Jian-Dong; Li, Xin-Xing; Zhou, Yu; Lü, Li; Qin, Hua

2015-10-01

An AlGaN/GaN high electron mobility transistor (HEMT) device is prepared by using a semiconductor nanofabrication process. A reflective radio-frequency (RF) readout circuit is designed and the HEMT device is assembled in an RF circuit through a coplanar waveguide transmission line. A gate capacitor of the HEMT and a surface-mounted inductor on the transmission line are formed to generate LC resonance. By tuning the gate voltage Vg, the variations of gate capacitance and conductance of the HEMT are reflected sensitively from the resonance frequency and the magnitude of the RF reflection signal. The aim of the designed RF readout setup is to develop a highly sensitive HEMT-based detector. Project supported by the National Natural Science Foundation of China (Grant No. 61107093), the Suzhou Science and Technology Project, China (Grant No. ZXG2012024), and the Youth Innovation Promotion Association, Chinese Academy of Sciences (Grant No. 2012243).

Relationship between Noctcaelador and Aesthetic Sensitivity: Art-Related Personality Factors Associated with College Students' Night-Sky Watching

ERIC Educational Resources Information Center

Kelly, William E.

2008-01-01

This study explored the relationship between positive attitudes and behaviors concerning night-sky watching (noctcaelador) and aesthetic sensitivity. College students (N = 106) completed the Noctcaelador Inventory (Kelly, 2004a) and a shortened version of the Sensitivity Questionnaire (Child, 1965). Noctcaelador was significantly, positively…

Combining magnetic nanoparticle with biotinylated nanobodies for rapid and sensitive detection of influenza H3N2

PubMed Central

2014-01-01

Our objective is to develop a rapid and sensitive assay based on magnetic beads to detect the concentration of influenza H3N2. The possibility of using variable domain heavy-chain antibodies (nanobody) as diagnostic tools for influenza H3N2 was investigated. A healthy camel was immunized with inactivated influenza H3N2. A nanobody library of 8 × 108 clones was constructed and phage displayed. After three successive biopanning steps, H3N2-specific nanobodies were successfully isolated, expressed in Escherichia coli, and purified. Sequence analysis of the nanobodies revealed that we possessed four classes of nanobodies against H3N2. Two nanobodies were further used to prepare our rapid diagnostic kit. Biotinylated nanobody was effectively immobilized onto the surface of streptavidin magnetic beads. The modified magnetic beads with nanobody capture specifically influenza H3N2 and can still be recognized by nanobodies conjugated to horseradish peroxidase (HRP) conjugates. Under optimized conditions, the present immunoassay exhibited a relatively high sensitive detection with a limit of 50 ng/mL. In conclusion, by combining magnetic beads with specific nanobodies, this assay provides a promising influenza detection assay to develop a potential rapid, sensitive, and low-cost diagnostic tool to screen for influenza infections. PMID:25328501

Combining magnetic nanoparticle with biotinylated nanobodies for rapid and sensitive detection of influenza H3N2

NASA Astrophysics Data System (ADS)

Zhu, Min; Hu, Yonghong; Li, Guirong; Ou, Weijun; Mao, Panyong; Xin, Shaojie; Wan, Yakun

2014-09-01

Our objective is to develop a rapid and sensitive assay based on magnetic beads to detect the concentration of influenza H3N2. The possibility of using variable domain heavy-chain antibodies (nanobody) as diagnostic tools for influenza H3N2 was investigated. A healthy camel was immunized with inactivated influenza H3N2. A nanobody library of 8 × 108 clones was constructed and phage displayed. After three successive biopanning steps, H3N2-specific nanobodies were successfully isolated, expressed in Escherichia coli, and purified. Sequence analysis of the nanobodies revealed that we possessed four classes of nanobodies against H3N2. Two nanobodies were further used to prepare our rapid diagnostic kit. Biotinylated nanobody was effectively immobilized onto the surface of streptavidin magnetic beads. The modified magnetic beads with nanobody capture specifically influenza H3N2 and can still be recognized by nanobodies conjugated to horseradish peroxidase (HRP) conjugates. Under optimized conditions, the present immunoassay exhibited a relatively high sensitive detection with a limit of 50 ng/mL. In conclusion, by combining magnetic beads with specific nanobodies, this assay provides a promising influenza detection assay to develop a potential rapid, sensitive, and low-cost diagnostic tool to screen for influenza infections.

New, simplified, interpolation method for estimation of microscopic nuclear masses based on the p-factor, P = N/sub P/N/sub N//(N/sub p/+N/sub n/)

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

Haustein, P.E.; Brenner, D.S.; Casten, R.F.

1987-12-10

A new semi-empirical method, based on the use of the P-factor (P = N/sub p/N/sub n//(N/sub p/+N/sub n/)), is shown to simplify significantly the systematics of atomic masses. Its uses is illustrated for actinide nuclei where complicated patterns of mass systematics seen in traditional plots versus Z, N, or isospin are consolidated and transformed into linear ones extending over long isotopic and isotonic sequences. The linearization of the systematics by this procedure provides a simple basis for mass prediction. For many unmeasured nuclei beyond the known mass surface, the P-factor method operates by interpolation among data for known nuclei rathermore » than by extrapolation, as is common in other mass models.« less

Measurement of Compression Factor and Error Sensitivity Factor of the Modified READ Facsimile Coding Technique.

DTIC Science & Technology

1980-08-01

Compression factor and error sensitivity together with statistical data have also been tabulated. This TIB is a companion drcument to NCS TIB’s 79-7...vu donner la priorit6 pour lour r~alisation. Chaque application est conf ice A un " chef do projet", responsable successivoment do sa conception. de son...pilote depend des r~sultats obtenus et fait I’objet d’une d~cision- de ’.a Direction Gdnerale. Ndanmoins, le chef do projet doit dOs le d~part consid~rer

Sensitivity analyses of factors influencing CMAQ performance for fine particulate nitrate.

PubMed

Shimadera, Hikari; Hayami, Hiroshi; Chatani, Satoru; Morino, Yu; Mori, Yasuaki; Morikawa, Tazuko; Yamaji, Kazuyo; Ohara, Toshimasa

2014-04-01

Improvement of air quality models is required so that they can be utilized to design effective control strategies for fine particulate matter (PM2.5). The Community Multiscale Air Quality modeling system was applied to the Greater Tokyo Area of Japan in winter 2010 and summer 2011. The model results were compared with observed concentrations of PM2.5 sulfate (SO4(2-)), nitrate (NO3(-)) and ammonium, and gaseous nitric acid (HNO3) and ammonia (NH3). The model approximately reproduced PM2.5 SO4(2-) concentration, but clearly overestimated PM2.5 NO3(-) concentration, which was attributed to overestimation of production of ammonium nitrate (NH4NO3). This study conducted sensitivity analyses of factors associated with the model performance for PM2.5 NO3(-) concentration, including temperature and relative humidity, emission of nitrogen oxides, seasonal variation of NH3 emission, HNO3 and NH3 dry deposition velocities, and heterogeneous reaction probability of dinitrogen pentoxide. Change in NH3 emission directly affected NH3 concentration, and substantially affected NH4NO3 concentration. Higher dry deposition velocities of HNO3 and NH3 led to substantial reductions of concentrations of the gaseous species and NH4NO3. Because uncertainties in NH3 emission and dry deposition processes are probably large, these processes may be key factors for improvement of the model performance for PM2.5 NO3(-). The Community Multiscale Air Quality modeling system clearly overestimated the concentration of fine particulate nitrate in the Greater Tokyo Area of Japan, which was attributed to overestimation of production of ammonium nitrate. Sensitivity analyses were conducted for factors associated with the model performance for nitrate. Ammonia emission and dry deposition of nitric acid and ammonia may be key factors for improvement of the model performance.

Development of the "Highly Sensitive Dog" questionnaire to evaluate the personality dimension "Sensory Processing Sensitivity" in dogs.

PubMed

Braem, Maya; Asher, Lucy; Furrer, Sibylle; Lechner, Isabel; Würbel, Hanno; Melotti, Luca

2017-01-01

In humans, the personality dimension 'sensory processing sensitivity (SPS)', also referred to as "high sensitivity", involves deeper processing of sensory information, which can be associated with physiological and behavioral overarousal. However, it has not been studied up to now whether this dimension also exists in other species. SPS can influence how people perceive the environment and how this affects them, thus a similar dimension in animals would be highly relevant with respect to animal welfare. We therefore explored whether SPS translates to dogs, one of the primary model species in personality research. A 32-item questionnaire to assess the "highly sensitive dog score" (HSD-s) was developed based on the "highly sensitive person" (HSP) questionnaire. A large-scale, international online survey was conducted, including the HSD questionnaire, as well as questions on fearfulness, neuroticism, "demographic" (e.g. dog sex, age, weight; age at adoption, etc.) and "human" factors (e.g. owner age, sex, profession, communication style, etc.), and the HSP questionnaire. Data were analyzed using linear mixed effect models with forward stepwise selection to test prediction of HSD-s by the above-mentioned factors, with country of residence and dog breed treated as random effects. A total of 3647 questionnaires were fully completed. HSD-, fearfulness, neuroticism and HSP-scores showed good internal consistencies, and HSD-s only moderately correlated with fearfulness and neuroticism scores, paralleling previous findings in humans. Intra- (N = 447) and inter-rater (N = 120) reliabilities were good. Demographic and human factors, including HSP score, explained only a small amount of the variance of HSD-s. A PCA analysis identified three subtraits of SPS, comparable to human findings. Overall, the measured personality dimension in dogs showed good internal consistency, partial independence from fearfulness and neuroticism, and good intra- and inter-rater reliability

The Naked Truth: The Face and Body Sensitive N170 Response Is Enhanced for Nude Bodies

PubMed Central

Hietanen, Jari K.; Nummenmaa, Lauri

2011-01-01

Recent event-related potential studies have shown that the occipitotemporal N170 component - best known for its sensitivity to faces - is also sensitive to perception of human bodies. Considering that in the timescale of evolution clothing is a relatively new invention that hides the bodily features relevant for sexual selection and arousal, we investigated whether the early N170 brain response would be enhanced to nude over clothed bodies. In two experiments, we measured N170 responses to nude bodies, bodies wearing swimsuits, clothed bodies, faces, and control stimuli (cars). We found that the N170 amplitude was larger to opposite and same-sex nude vs. clothed bodies. Moreover, the N170 amplitude increased linearly as the amount of clothing decreased from full clothing via swimsuits to nude bodies. Strikingly, the N170 response to nude bodies was even greater than that to faces, and the N170 amplitude to bodies was independent of whether the face of the bodies was visible or not. All human stimuli evoked greater N170 responses than did the control stimulus. Autonomic measurements and self-evaluations showed that nude bodies were affectively more arousing compared to the other stimulus categories. We conclude that the early visual processing of human bodies is sensitive to the visibility of the sex-related features of human bodies and that the visual processing of other people's nude bodies is enhanced in the brain. This enhancement is likely to reflect affective arousal elicited by nude bodies. Such facilitated visual processing of other people's nude bodies is possibly beneficial in identifying potential mating partners and competitors, and for triggering sexual behavior. PMID:22110574

Distinct Contributory Factors Determine Basophil-Allergen Sensitivity in Grass Pollen Rhinitis and in Anaphylactic Wasp Venom Allergy.

PubMed

Korošec, Peter; Šilar, Mira; Kopač, Peter; Eržen, Renato; Zidarn, Mihaela; Košnik, Mitja

2016-01-01

We sought to determine whether basophil-allergen sensitivity could be transferred to donor basophils by passive IgE sensitisation in allergic rhinitis and anaphylactic Hymenoptera venom hypersensitivity. We studied 15 wasp venom-, 19 grass pollen- and 2 house dust mite-allergic patients, 2 healthy donors, and 8 wasp venom-allergic donors. In all subjects, we first evaluated the initial basophil response to wasp venom, grass pollen, or house dust mite allergen. Donor basophils were then stripped, sensitised with the different patients' serum IgE, and challenged with the corresponding allergen. The CD63 response of donor basophils was then compared with initial basophil responses. In wasp venom-allergic subjects, the IgE transfer did not reflect the initial basophil-allergen sensitivity, because the venom IgE of subjects with high or low basophil sensitivity induced comparable responsiveness in healthy donor basophils. Furthermore, vice versa, when we sensitised the donor basophils of wasp venom-allergic individuals with different wasp venom or house dust mite IgE, we demonstrated that their response was predictable by their initial basophil allergen sensitivity. In the rhinitis allergy model, the IgE transfer correlated with the patients' initial basophil responsiveness because the grass pollen IgE of the subjects with high basophil allergen sensitivity induced significantly higher responsiveness of donor basophils than the IgE of subjects with initially low basophil allergen sensitivity. Our results suggest that basophil allergen sensitivity evaluated by flow-cytometric CD63 analysis depends on two distinct contribution factors. In anaphylactic Hymenoptera allergy, the major factor was intrinsic cellular sensitivity, whereas in pollen allergy, the major factor was allergen-specific IgE on the cell surface. © 2016 S. Karger AG, Basel.

Biosurfactant mannosyl-erythritol lipid inhibits secretion of inflammatory mediators from RBL-2H3 cells.

PubMed

Morita, Yosuke; Tadokoro, Satoshi; Sasai, Masao; Kitamoto, Dai; Hirashima, Naohide

2011-12-01

Biosurfactant mannosyl-erythritol lipids (MELs) are glycolipids produced by microbes that have various biological activities. It has been reported that MELs exhibit excellent surface-activity and also various bioactivities, such as induction of cell differentiation and apoptosis. However, little is known about their action related to drug discovery or drug seeds. We investigated the effects of MELs on the secretion of inflammatory mediators from mast cells that play a central role in allergic responses. Mast cells secrete three kinds of inflammatory mediators and we quantified these secreted mediators by photometer or ELISA. The action mechanisms of MELs were studied by Ca(2+)-sensitive fluorescence dye and Western blotting of phosphorylated proteins. MELs inhibited exocytotic release by antigen stimulation in a dose-dependent manner. We also found that MELs inhibited antigen-induced secretion of leukotriene C(4) and cytokine TNF-α (tumor necrosis factor-α). The inhibitory action of MELs on mediator secretion was mediated by inhibition of Ca(2+) increase, phosphorylation of MAP kinases and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) that serve as a molecular machinery for exocytotic membrane fusion. MELs have anti-inflammatory action inhibiting the secretion of inflammatory mediators from mast cells. MELs affects two of major intracellular signaling pathways including Ca(2+) increase and MAP kinases. MELs also inhibited the phosphorylation of SNARE proteins that is crucial for not only exocytosis but also intracellular vesicular trafficking. 2011 Elsevier B.V. All rights reserved.

Comparison between several insulin sensitivity indices and metabolic risk factors in overweight and obese postmenopausal women: a MONET study.

PubMed

Malita, F M; Messier, V; Lavoie, J-M; Bastard, J-P; Rabasa-Lhoret, R; Karelis, A D

2010-03-01

The purpose of this study was to compare the relationship of several insulin sensitivity indices with cardiometabolic risk factors in overweight and obese postmenopausal women. This was a cross-sectional study involving 137 overweight and obese postmenopausal women (age: 57.7+/-4.8 yrs; body mass index: 32.4+/-4.6 kg/m(2); body fat: 38.6+/-9.2 kg). Insulin sensitivity was determined by the euglycaemic-hyperinsulinemic (EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived indices (Stumvoll, Matsuda and SI(is)) and fasting surrogate indices (HOMA, QUICKI). Cardiometabolic risk factors included: body composition and visceral fat that were measured using dual energy X-ray absorptiometry and computed tomography, respectively. Peak oxygen consumption, lower body muscle strength (using weight training equipment), physical activity energy expenditure (doubly labeled water), plasma lipids and C-reactive protein were also measured. Correlations of insulin sensitivity indices with metabolic risk factors showed some similarities, however, a wide range of variations were also observed. Furthermore, our results showed that visceral fat was the primary predictor for surrogate and OGTT indices, explaining 15-28% of the variance and the triglycerides/HDL-C ratio was the primary predictor for the EH clamp indices, explaining 15-17% of the variance. The present study indicates that the different methods of measuring and/or expressing insulin sensitivity display variations for associations with cardiometabolic risk factors. Therefore, interpretations of relationships between insulin sensitivity indices and cardiometabolic risk factors should take into account the method used to estimate and express insulin sensitivity. (c) 2009 Elsevier B.V. All rights reserved.

Temperature sensitivity on growth and/or replication of H1N1, H1N2 and H3N2 influenza A viruses isolated from pigs and birds in mammalian cells.

PubMed

Massin, Pascale; Kuntz-Simon, Gaëlle; Barbezange, Cyril; Deblanc, Céline; Oger, Aurélie; Marquet-Blouin, Estelle; Bougeard, Stéphanie; van der Werf, Sylvie; Jestin, Véronique

2010-05-19

Influenza A viruses have been isolated from a wide range of animal species, aquatic birds being the reservoir for their genetic diversity. Avian influenza viruses can be transmitted to humans, directly or indirectly through an intermediate host like pig. This study aimed to define in vitro conditions that could prove useful to evaluate the potential of influenza viruses to adapt to a different host. Growth of H1N1, H1N2 and H3N2 influenza viruses belonging to different lineages isolated from birds or pigs prior to 2005 was tested on MDCK or NPTr cell lines in the presence or absence of exogenous trypsin. Virus multiplication was compared at 33, 37 and 40 degrees C, the infection site temperatures in human, swine and avian hosts, respectively. Temperature sensitivity of PB2-, NP- and M-RNA replication was also tested by quantitative real-time PCR. Multiplication of avian viruses was cold-sensitive, whatever cell type. By contrast, temperature sensitivity of swine viruses was found to depend on the virus and the host cell: for an H1N1 swine isolate from 1982, multiplication was cold-sensitive on NPTr cells and undetectable at 40 degrees C. From genetic analyses, it appears that temperature sensitivity could involve other residues than PB2 residue 627 and could affect other steps of the replication cycle than replication. Copyright 2009 Elsevier B.V. All rights reserved.

Factorizing the motion sensitivity function into equivalent input noise and calculation efficiency.

PubMed

Allard, Rémy; Arleo, Angelo

2017-01-01

The photopic motion sensitivity function of the energy-based motion system is band-pass peaking around 8 Hz. Using an external noise paradigm to factorize the sensitivity into equivalent input noise and calculation efficiency, the present study investigated if the variation in photopic motion sensitivity as a function of the temporal frequency is due to a variation of equivalent input noise (e.g., early temporal filtering) or calculation efficiency (ability to select and integrate motion). For various temporal frequencies, contrast thresholds for a direction discrimination task were measured in presence and absence of noise. Up to 15 Hz, the sensitivity variation was mainly due to a variation of equivalent input noise and little variation in calculation efficiency was observed. The sensitivity fall-off at very high temporal frequencies (from 15 to 30 Hz) was due to a combination of a drop of calculation efficiency and a rise of equivalent input noise. A control experiment in which an artificial temporal integration was applied to the stimulus showed that an early temporal filter (generally assumed to affect equivalent input noise, not calculation efficiency) could impair both the calculation efficiency and equivalent input noise at very high temporal frequencies. We conclude that at the photopic luminance intensity tested, the variation of motion sensitivity as a function of the temporal frequency was mainly due to early temporal filtering, not to the ability to select and integrate motion. More specifically, we conclude that photopic motion sensitivity at high temporal frequencies is limited by internal noise occurring after the transduction process (i.e., neural noise), not by quantal noise resulting from the probabilistic absorption of photons by the photoreceptors as previously suggested.

Oral Application of Magnesium-L-Threonate Attenuates Vincristine-induced Allodynia and Hyperalgesia by Normalization of Tumor Necrosis Factor-α/Nuclear Factor-κB Signaling.

PubMed

Xu, Ting; Li, Dai; Zhou, Xin; Ouyang, Han-Dong; Zhou, Li-Jun; Zhou, Hang; Zhang, Hong-Mei; Wei, Xu-Hong; Liu, Guosong; Liu, Xian-Guo

2017-06-01

Antineoplastic agents, including vincristine, often induce neuropathic pain and magnesium deficiency clinically, but the causal link between them has not been determined. No drug is available for treating this form of neuropathic pain. Injection of vincristine (0.1 mg · kg · day, intraperitoneally, for 10 days) was used to induce nociceptive sensitization, which was accessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats. Magnesium-L- threonate was administered through drinking water (604 mg · kg · day). Extracellular and intracellular free Mg were measured by Calmagite chromometry and flow cytometry. Molecular biologic and electrophysiologic experiments were performed to expose the underlying mechanisms. Vincristine injection induced allodynia and hyperalgesia (n = 12), activated tumor necrosis factor-α/nuclear factor-κB signaling, and reduced free Mg in cerebrospinal fluid by 21.7 ± 6.3% (mean ± SD; n = 13) and in dorsal root ganglion neurons by 27 ± 6% (n = 11). Reducing Mg activated tumor necrosis factor-α/nuclear factor-κB signaling in cultured dorsal root ganglion neurons. Oral application of magnesium-L-threonate prevented magnesium deficiency and attenuated both activation of tumor necrosis factor-α/nuclear factor-κB signaling and nociceptive sensitization (n = 12). Mechanistically, vincristine induced long-term potentiation at C-fiber synapses, up-regulated N-methyl-D-aspartate receptor type 2B subunit of N-methyl-D-aspartate receptor, and led to peptidergic C-fiber sprouting in spinal dorsal horn (n = 6 each). The vincristine-induced pathologic plasticity was blocked by intrathecal injection of nuclear factor-κB inhibitor (n = 6), mimicked by tumor necrosis factor-α, and substantially prevented by oral magnesium-L-threonate (n = 5). Vincristine may activate tumor necrosis factor-α/nuclear factor-κB pathway by reduction of intracellular magnesium, leading to spinal pathologic plasticity and

Nitrogen-Deficiency Stress Induces Protein Expression Differentially in Low-N Tolerant and Low-N Sensitive Maize Genotypes

PubMed Central

Nazir, Muslima; Pandey, Renu; Siddiqi, Tariq O.; Ibrahim, Mohamed M.; Qureshi, Mohammad I.; Abraham, Gerard; Vengavasi, Krishnapriya; Ahmad, Altaf

2016-01-01

Nitrogen (N) is essential for proper plant growth and its application has proven to be critical for agricultural produce. However, for unavoidable economic and environmental problems associated with excessive use of N-fertilizers, it is an urgent demand to manage application of fertilizers. Improving the N-use efficiency (NUE) of crop plants to sustain productivity even at low N levels is the possible solution. In the present investigation, contrasting low-N sensitive (HM-4) and low-N tolerant (PEHM-2) genotypes were identified and used for comparative proteome-profiling of leaves under optimum and low N as well as restoration of low N on 3rd (NR3) and 5th (NR5) days after re-supplying N. The analysis of differential expression pattern of proteins was performed by 2-D gel electrophoresis. Significant variations in the expression of proteins were observed under low N, which were genotype specific. In the leaf proteome, 25 spots were influenced by N treatment and four spots were different between the two genotypes. Most of the proteins that were differentially accumulated in response to N level and were involved in photosynthesis and metabolism, affirming the relationship between N and carbon metabolism. In addition to this, greater intensity of some defense proteins in the low N tolerant genotype was found that may have a possible role in imparting it tolerance under N starvation conditions. The new insights generated on maize proteome in response to N-starvation and restoration would be useful toward improvement of NUE in maize. PMID:27047497

Engineering botulinum neurotoxin domains for activation by toxin light chain.

PubMed

Stancombe, Patrick R; Masuyer, Geoffrey; Birch-Machin, Ian; Beard, Matthew; Foster, Keith A; Chaddock, John A; Acharya, K Ravi

2012-02-01

Targeted secretion inhibitors (TSI) are a new class of biopharmaceuticals designed from a botulinum neurotoxin protein scaffold. The backbone consists of the 50-kDa endopeptidase light chain and translocation domain (N-terminal portion of the heavy chain), lacks neuronal toxicity, but retains the ability to target cytoplasmic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. TSI are produced as single-chain proteins and then cleaved post-translationally to generate functional heterodimers. Precise proteolytic cleavage is essential to activate the protein to a dichain form. TSI are themselves highly specific proteases. We have exploited this activity to create self-activating enzymes by replacing the native proteolytic site with a substrate SNARE peptide for the TSI protease. We have also created cross-activating backbones. By replacing the proteolytic activation site in one backbone with the substrate SNARE peptide for another serotype, controlled activation is achieved. SNARE peptides encompassing the whole of the coiled-coil region enabled complete activation and assembly of the dichain backbone. These engineered TSI backbones are capable of translocating their enzymatic domains to target intracellular SNARE proteins. They are also investigative tools with which to further the understanding of endopeptidase activity of light chain in SNARE interactions. © 2011 Syntaxin Ltd. Journal compilation © 2011 FEBS.

The K+/site and H+/site stoichiometry of mitochondrial electron transport.

PubMed

Reynafarje, B; Lehninger, A L

1978-09-25

Electrode measurements of the average number of H+ ejected and K+ taken up (in the presence of valinomycin) per pair of electrons passing the energy-conserving sites of the respiratory chain of rat liver and rat heart mitochondria have given identical values of the H+/site and 5+/site ratios very close to 4 in the presence of N-ethylmaleimide, an inhibitor of interfering respiration-coupled uptake of H+ + H2PO4-. The K+/site uptake ratio of 4 not only shows that inward movement of K+ provides quantitative charge-compensation for the 4 H+ ejected, but also confirms that 4 charges are separated per pair of electrons per site. When N-ethylmaleimide is omitted, the H+/site ejection ratio is depressed, because of the interfering secondary uptake of H/+ with H2PO4- on the phosphate carrier, but the K+/site uptake ratio remains at 4.0. Addition of phosphate or acetate, which can carry H+ into respiring mitochondria, further depresses the H+/site ratio, but does not affect the K+/site ratio, which remains at 4.0. These and other considerations thus confirm our earlier stoichiometric measurements that the average H+/site ratio is 4.0 and also show that the K+/site uptake ratio can be used as a measure of the intrinsic H+/site ratio, regardless of the presence of phosphate in the medium and without the necessity of adding N-ethylmaleimide or other inhibitors of H+ + H2PO4- transport.

Factor Structure and Psychometric Properties of the Anxiety Sensitivity Index in a Sample of Croatian Adults

ERIC Educational Resources Information Center

Jurin, Tanja; Jokic-Begic, Natasa; Korajlija, Anita Lauri

2012-01-01

Anxiety sensitivity (AS) refers to a person's tendency to fear anxiety-related symptoms due to the belief that these symptoms may have harmful consequences. The most widely used operationalization of AS in adults is the Anxiety Sensitivity Index (ASI). The factor structure, gender stability, and psychometric properties of the ASI in a sample of…

Expectations about person identity modulate the face-sensitive N170.

PubMed

Johnston, Patrick; Overell, Anne; Kaufman, Jordy; Robinson, Jonathan; Young, Andrew W

2016-12-01

Identifying familiar faces is a fundamentally important aspect of social perception that requires the ability to assign very different (ambient) images of a face to a common identity. The current consensus is that the brain processes face identity at approximately 250-300 msec following stimulus onset, as indexed by the N250 event related potential. However, using two experiments we show compelling evidence that where experimental paradigms induce expectations about person identity, changes in famous face identity are in fact detected at an earlier latency corresponding to the face-sensitive N170. In Experiment 1, using a rapid periodic stimulation paradigm presenting highly variable ambient images, we demonstrate robust effects of low frequency, periodic face-identity changes in N170 amplitude. In Experiment 2, we added infrequent aperiodic identity changes to show that the N170 was larger to both infrequent periodic and infrequent aperiodic identity changes than to high frequency identities. Our use of ambient stimulus images makes it unlikely that these effects are due to adaptation of low-level stimulus features. In line with current ideas about predictive coding, we therefore suggest that when expectations about the identity of a face exist, the visual system is capable of detecting identity mismatches at a latency consistent with the N170. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulation of Synaptic Transmission by RAB-3 and RAB-27 in Caenorhabditis elegans

PubMed Central

Mahoney, Timothy R.; Liu, Qiang; Itoh, Takashi; Luo, Shuo; Hadwiger, Gayla; Vincent, Rose; Wang, Zhao-Wen; Fukuda, Mitsunori

2006-01-01

Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function. PMID:16571673

The N170 component is sensitive to face-like stimuli: a study of Chinese Peking opera makeup.

PubMed

Liu, Tiantian; Mu, Shoukuan; He, Huamin; Zhang, Lingcong; Fan, Cong; Ren, Jie; Zhang, Mingming; He, Weiqi; Luo, Wenbo

2016-12-01

The N170 component is considered a neural marker of face-sensitive processing. In the present study, the face-sensitive N170 component of event-related potentials (ERPs) was investigated with a modified oddball paradigm using a natural face (the standard stimulus), human- and animal-like makeup stimuli, scrambled control images that mixed human- and animal-like makeup pieces, and a grey control image. Nineteen participants were instructed to respond within 1000 ms by pressing the ' F ' or ' J ' key in response to the standard or deviant stimuli, respectively. We simultaneously recorded ERPs, response accuracy, and reaction times. The behavioral results showed that the main effect of stimulus type was significant for reaction time, whereas there were no significant differences in response accuracies among stimulus types. In relation to the ERPs, N170 amplitudes elicited by human-like makeup stimuli, animal-like makeup stimuli, scrambled control images, and a grey control image progressively decreased. A right hemisphere advantage was observed in the N170 amplitudes for human-like makeup stimuli, animal-like makeup stimuli, and scrambled control images but not for grey control image. These results indicate that the N170 component is sensitive to face-like stimuli and reflect configural processing in face recognition.

Childhood Adversity and Pain Sensitization.

PubMed

You, Dokyoung Sophia; Meagher, Mary W

Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

Improvement of N-phthaloylchitosan based gel polymer electrolyte in dye-sensitized solar cells using a binary salt system.

PubMed

Yusuf, S N F; Azzahari, A D; Selvanathan, V; Yahya, R; Careem, M A; Arof, A K

2017-02-10

A binary salt system utilizing lithium iodide (LiI) as the auxiliary component has been introduced to the N-phthaloylchitosan (PhCh) based gel polymer electrolyte consisting of ethylene carbonate (EC), dimethylformamide (DMF), tetrapropylammonium iodide (TPAI), and iodine (I 2 ) in order to improve the performance of dye-sensitized solar cell (DSSC) with efficiency of 6.36%, photocurrent density, J SC of 17.29mAcm -2 , open circuit voltage, V OC of 0.59V and fill factor, FF of 0.62. This efficiency value is an improvement from the 5.00% performance obtained by the DSSC consisting of only TPAI single salt system. The presence of the LiI in addition to the TPAI improves the charge injection rates and increases the iodide contribution to the total conductivity and both factors contribute to the increase in efficiency of the DSSC. The interaction behavior between polymer-plasticizer-salt was thoroughly investigated using EIS, FTIR spectroscopy and XRD. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Anxiety Sensitivity Index--Revised: Confirmatory Factor Analyses, Structural Invariance in Caucasian and African American Samples, and Score Reliability and Validity

ERIC Educational Resources Information Center

Arnau, Randolph C.; Broman-Fulks, Joshua J.; Green, Bradley A.; Berman, Mitchell E.

2009-01-01

The most commonly used measure of anxiety sensitivity is the 36-item Anxiety Sensitivity Index--Revised (ASI-R). Exploratory factor analyses have produced several different factors structures for the ASI-R, but an acceptable fit using confirmatory factor analytic approaches has only been found for a 21-item version of the instrument. We evaluated…

A practical and highly sensitive C3N4-TYR fluorescent probe for convenient detection of dopamine

NASA Astrophysics Data System (ADS)

Li, Hao; Yang, Manman; Liu, Juan; Zhang, Yalin; Yang, Yanmei; Huang, Hui; Liu, Yang; Kang, Zhenhui

2015-07-01

The C3N4-tyrosinase (TYR) hybrid is a highly accurate, sensitive and simple fluorescent probe for the detection of dopamine (DOPA). Under optimized conditions, the relative fluorescence intensity of C3N4-TYR is proportional to the DOPA concentration in the range from 1 × 10-3 to 3 × 10-8 mol L-1 with a correlation coefficient of 0.995. In the present system, the detection limit achieved is as low as 3 × 10-8 mol L-1. Notably, these quantitative detection results for clinical samples are comparable to those of high performance liquid chromatography. Moreover, the enzyme-encapsulated C3N4 sensing arrays on both glass slide and test paper were evaluated, which revealed sensitive detection and excellent stability. The results reported here provide a new approach for the design of a multifunctional nanosensor for the detection of bio-molecules.The C3N4-tyrosinase (TYR) hybrid is a highly accurate, sensitive and simple fluorescent probe for the detection of dopamine (DOPA). Under optimized conditions, the relative fluorescence intensity of C3N4-TYR is proportional to the DOPA concentration in the range from 1 × 10-3 to 3 × 10-8 mol L-1 with a correlation coefficient of 0.995. In the present system, the detection limit achieved is as low as 3 × 10-8 mol L-1. Notably, these quantitative detection results for clinical samples are comparable to those of high performance liquid chromatography. Moreover, the enzyme-encapsulated C3N4 sensing arrays on both glass slide and test paper were evaluated, which revealed sensitive detection and excellent stability. The results reported here provide a new approach for the design of a multifunctional nanosensor for the detection of bio-molecules. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03316k

IFN-{gamma} sensitizes MIN6N8 insulinoma cells to TNF-{alpha}-induced apoptosis by inhibiting NF-{kappa}B-mediated XIAP upregulation

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

Kim, Hun Sik; Kim, Sunshin; Lee, Myung-Shik

2005-10-28

Although X-linked inhibitor of apoptosis protein (XIAP) is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic {beta}-cell apoptosis remains unclear. Here, we found that: (i) XIAP level was inversely correlated with tumor necrosis factor (TNF)-{alpha}-induced apoptosis in MIN6N8 insulinoma cells; (ii) adenoviral XIAP overexpression abrogated the TNF-{alpha}-induced apoptosis through inhibition of caspase activity; (iii) downregulation of XIAP by antisense oligonucleotide or Smac peptide sensitized MIN6N8 cells to TNF-{alpha}-induced apoptosis; (iv) XIAP expression was induced by TNF-{alpha} through a nuclear factor-{kappa}B (NF-{kappa}B)-dependent pathway, and interferon (IFN)-{gamma} prevented such an induction in amore » manner independent of NF-{kappa}B, which presents a potential mechanism underlying cytotoxic IFN-{gamma}/TNF-{alpha} synergism. Taken together, our results suggest that XIAP is an important modulator of TNF-{alpha}-induced apoptosis of MIN6N8 cells, and XIAP regulation in pancreatic {beta}-cells might play an important role in pancreatic {beta}-cell apoptosis and in the pathogenesis of type 1 diabetes.« less

Cilnidipine, an L/N-type calcium channel blocker prevents acquisition and expression of ethanol-induced locomotor sensitization in mice.

PubMed

Bhutada, Pravinkumar; Mundhada, Yogita; Patil, Jayshree; Rahigude, Anand; Zambare, Krushna; Deshmukh, Prashant; Tanwar, Dhanshree; Jain, Kishor

2012-04-11

Several evidences indicated the involvement of L- and N-type calcium channels in behavioral effects of drugs of abuse, including ethanol. Calcium channels are implicated in ethanol-induced behaviors and neurochemical responses. Calcium channel antagonists block the psychostimulants induced behavioral sensitization. Recently, it is demonstrated that L-, N- and T-type calcium channel blockers attenuate the acute locomotor stimulant effects of ethanol. However, no evidence indicated the role of calcium channels in ethanol-induced psychomotor sensitization. Therefore, present study evaluated the influence of cilnidipine, an L/N-type calcium channel blocker on acquisition and expression of ethanol-induced locomotor sensitization. The results revealed that cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) attenuates the expression of sensitization to locomotor stimulant effect of ethanol (2.0g/kg, i.p.), whereas pre- treatment of cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) during development of sensitization blocks acquisition and attenuates expression of sensitization to locomotor stimulant effect of ethanol. Cilnidipine per se did not influence locomotor activity in tested doses. Further, cilnidipine had no influence on effect of ethanol on rotarod performance. These results support the hypothesis that neuroadaptive changes in calcium channels participate in the acquisition and the expression of ethanol-induced locomotor sensitization. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hepatocyte growth factor sensitizes brain tumors to c-MET kinase inhibition

PubMed Central

Zhang, Ying; Farenholtz, Kaitlyn E.; Yang, Yanzhi; Guessous, Fadila; diPierro, Charles G.; Calvert, Valerie S.; Deng, Jianghong; Schiff, David; Xin, Wenjun; Lee, Jae K.; Purow, Benjamin; Christensen, James; Petricoin, Emanuel; Abounader, Roger

2013-01-01

Purpose The receptor tyrosine kinase (RTK) c-MET and its ligand hepatocyte growth factor (HGF) are deregulated and promote malignancy in cancer and brain tumors. Consequently, clinically applicable c-MET inhibitors have been developed. The purpose of this study was to investigate the not well known molecular determinants that predict responsiveness to c-MET inhibitors, and to explore new strategies for improving inhibitor efficacy in brain tumors. Experimental design We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells (GSCs), and established cell line-derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done. We also explored new approaches for improving the efficacy of the inhibitors in vitro and in vivo. Results We found that HGF co-expression is a key predictor of response to c-MET inhibition among the examined factors, and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET inhibition in responsive and non-responsive cells. Surprisingly, we also found that short pre-treatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the anti-tumor effects of c-MET inhibition. We observed a similar ligand-induced sensitization effect to an EGFR small molecule kinase inhibitor. Conclusions These findings allow the identification of a subset of patients that will be responsive to c-MET inhibition, and propose ligand pre-treatment as a potential new strategy for improving the anti-cancer efficacy of RTK inhibitors. PMID:23386689

Porous silicon ring resonator for compact, high sensitivity biosensing applications

DOE PAGES

Rodriguez, Gilberto A.; Hu, Shuren; Weiss, Sharon M.

2015-01-01

A ring resonator is patterned on a porous silicon slab waveguide to produce a compact, high quality factor biosensor with a large internal surface area available for enhanced recognition of biological and chemical molecules. The porous nature of the ring resonator allows molecules to directly interact with the guided mode. Quality factors near 10,000 were measured for porous silicon ring resonators with a radius of 25 μm. A bulk detection sensitivity of 380 nm/RIU was measured upon exposure to salt water solutions. Specific detection of nucleic acid molecules was demonstrated with a surface detection sensitivity of 4 pm/nM.

Dimensions of Culturally Sensitive Factors in the Design and Development of Learning Objects

ERIC Educational Resources Information Center

Qi, Mei; Boyle, Tom

2010-01-01

Open educational resources (OERs) are designed to be globally reusable. Yet comparatively little attention has been given to the cultural issues. This paper addresses the issue of culturally sensitive factors that may influence the design of reusable learning objects. These influences are often subtle and hard to manage. The paper proposes a…

ROLE OF INSULIN SENSITIZERS ON CARDIOVASCULAR RISK FACTORS IN POLYCYSTIC OVARIAN SYNDROME: A META-ANALYSIS.

PubMed

Thethi, Tina K; Katalenich, Bonnie; Nagireddy, Prathima; Chabbra, Pankdeep; Kuhadiya, Nitesh; Fonseca, Vivian

2015-06-01

Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and hyperlipidemia, which are predisposing factors for type 2 diabetes mellitus and CV disease. The aim of this meta-analysis is to examine the effect of insulin sensitizers on clinical and biochemical features of PCOS and risk factors for CV disease. A systematic literature review was conducted, and randomized controlled clinical trials were identified by a search of bibliographic databases: Medline database (from 1966 forward), EMBASE (January 1985 forward), and Cochrane Central Register of Controlled Trials. Reviews of reference lists further identified candidate trials. Data was independently abstracted in duplicate by 2 investigators using a standardized data-collection form. Articles without a comparison group and randomization allocation were excluded. Reviewers worked independently and in duplicate to determine the methodological quality of trials, then collected data on patient characteristics, interventions, and outcomes. Of 455 studies, 44 trials were eligible. A random effects model was used. Significant unadjusted results favoring treatment with insulin sensitizers were obtained for body mass index (BMI) (effect size [ES] of 0.58), waist to hip ratio (WHR) (ES of 0.02), low-density-lipoprotein cholesterol (LDL-C) (ES of 0.11), fasting insulin (ES of 2.82), fasting glucose (ES of 0.10), free testosterone (ES of 1.88), and androstenedione level (ES of 0.76). Treatment with insulin sensitizers in women with PCOS results in improvement in CV factors such as BMI, WHR, LDL-C, fasting insulin, glucose, free testosterone, and androstenedione.

Factors affecting ozone sensitivity of tobacco Bel-W3 seedlings.

PubMed

Cheng, Ji-Fang; Sun, En-Jang

2013-12-01

Since 1962, the tobacco variety Nicotiana tabacum cv. Bel-W3 has been used worldwide as an ozone (O3) bio-indicator. The use of indicator plants to monitor O3 pollution has proven problematic when trying to correlate the severity of injury to ambient O3 concentration. The aim of the present study was to study factors affecting the O3 sensitivity of Nicotiana tabacum cv. Bel-W3 seedlings. In chronic O3 pre-exposure tests, tobacco plants were cultured from seeds in charcoal-filtered air (CF) and noncharcoal-filtered ambient air (NF) for 21 days. During these periods, the mean O3 concentrations of the CF and NF treatments were 5.5 ± 0.2 and 14.7 ± 0.4 ppb h -1 , respectively (p < 0.001). At the end of the culturing period, no O3-induced foliar injury was observed in any of the plants. The O3 sensitivity of the tobacco plants was determined by exposing the plants to 150 ppb O3 for 8 hours in a fumigation chamber. The leaf injury index percentages (LII%) of indicator plants via the CF and NF treatments were 58.0 ± 3.2% and 43.1 ± 4.0%, respectively (p < 0.01). Twenty-one-day-old tobacco seedlings grown in NF air were used to test the effects of exposed leaves on O3 sensitivity. After removing the cotyledons and all true leaves, the NF seedlings with their apical buds intact were transferred to CF air. After another 7 days of culturing, the newly developed leaves were approximately 1 cm in length. After O3 treatment, the LII% values of the newly developed leaves from the untreated and defoliated seedlings were 2.5 ± 1.7% and 27.6 ± 1.3%, respectively (p < 0.001). In acute O3 exposure tests, 21-day-old seedlings grown in CF air were fumigated with 150 ppb O3 for 8 hours in one day or for 4 hours/day in two consecutive days. The LII% values for the two groups were 63.5 ± 7.4% and 20.1 ± 4.3%, respectively (p < 0.001). The present findings suggest that plant pre-exposure to O3 is a critical factor influencing

ETD Outperforms CID and HCD in the Analysis of the Ubiquitylated Proteome

NASA Astrophysics Data System (ADS)

Porras-Yakushi, Tanya R.; Sweredoski, Michael J.; Hess, Sonja

2015-09-01

Comprehensive analysis of the ubiquitylome is a prerequisite to fully understand the regulatory role of ubiquitylation. However, the impact of key mass spectrometry parameters on ubiquitylome analyses has not been fully explored. In this study, we show that using electron transfer dissociation (ETD) fragmentation, either exclusively or as part of a decision tree method, leads to ca. 2-fold increase in ubiquitylation site identifications in K-ɛ-GG peptide-enriched samples over traditional collisional-induced dissociation (CID) or higher-energy collision dissociation (HCD) methods. Precursor ions were predominantly observed as 3+ charged species or higher and in a mass range 300-1200 m/z. N-ethylmaleimide was used as an alkylating agent to reduce false positive identifications resulting from overalkylation with halo-acetamides. These results demonstrate that the application of ETD fragmentation, in addition to narrowing the mass range and using N-ethylmaleimide yields more high-confidence ubiquitylation site identification than conventional CID and HCD analysis.

N-methyl-N'-nitro-N-nitrosoguanidine interferes with the epidermal growth factor receptor-mediated signaling pathway.

PubMed

Gao, Zhihua; Yang, Jun; Huang, Yun; Yu, Yingnian

2005-03-01

Many environmental factors, such as ultraviolet (UV) and arsenic, can induce the clustering of cell surface receptors, including epidermal growth factor receptor (EGFR). This is accompanied by the phosphorylation of the receptors and the activation of ensuing cellular signal transduction pathways, which are implicated in the various cellular responses caused by the exposure to these factors. In this study, we have shown that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), an alkylating agent, also induced the clustering of EGFR in human amnion FL cells, which was similar in morphology to that of epidermal growth factor treatment. However, MNNG treatment did not activate Ras, the downstream mediator in EGFR signaling pathway, as compared to EGF treatment. The autophosphorylation of tyrosine residues Y1068 and Y1173 at the intracellular domain of EGFR, which is related to Ras activation under EGF treatment, was also not observed by MNNG exposure. Interestingly, although MNNG did not affect the binding of EGF to EGFR, MNNG can interfere with EGF function. For instance, pre-incubating FL cells with MNNG inhibited the autophosphorylation of EGFR by EGF treatment, as well as the activation of Ras. In addition, the phosphorylation of Y845 on EGFR by EGF, which is mediated through c-Src or related kinases but not autophosphorylation, was also affected by MNNG. Therefore, MNNG may influence the tyrosine kinase activity as well as the phosphorylation of EGFR through its interaction with EGFR.

Prevalence of and risk factors for latex sensitization in patients with spina bifida.

PubMed

Bernardini, R; Novembre, E; Lombardi, E; Mezzetti, P; Cianferoni, A; Danti, A D; Mercurella, A; Vierucci, A

1998-11-01

We determined the prevalence of and risk factors for latex sensitization in patients with spina bifida. A total of 59 consecutive subjects 2 to 40 years old with spina bifida answered a questionnaire, and underwent a latex skin prick test and determination of serum IgE specific for latex by RAST CAP radioimmunoassay. We also noted the relationships of total serum IgE skin prick tests to common air and food allergens. In addition, skin prick plus prick tests were also done with fresh foods, including kiwi, pear, orange, almond, pineapple, apple, tomato and banana. Latex sensitization was present in 15 patients (25%) according to the presence of IgE specific to latex, as detected by a skin prick test in 9 and/or RAST CAP in 13. Five latex sensitized patients (33.3%) had clinical manifestations, such as urticaria, conjuctivitis, angioedema, rhinitis and bronchial asthma, while using a latex glove and inflating a latex balloon. Atopy was present in 21 patients (35.6%). In 14 patients (23%) 1 or more skin tests were positive for fresh foods using a prick plus prick technique. Tomato, kiwi, and pear were the most common skin test positive foods. Univariate analysis revealed that a history of 5 or more operations, atopy and positive prick plus prick tests results for pear and kiwi were significantly associated with latex sensitization. Multivariate analysis demonstrated that only atopy and a history of 5 or more operations were significantly and independently associated with latex sensitization. A fourth of the patients with spina bifida were sensitized to latex. Atopy and an elevated number of operations were significant and independent predictors of latex sensitization in these cases.

Facile and sensitive determination of N-nitrosamines in food samples by high-performance liquid chromatography via combining fluorescent labeling with dispersive liquid-liquid microextraction.

PubMed

Lu, Shuaimin; Wu, Di; Li, Guoliang; Lv, Zhengxian; Gong, Peiwei; Xia, Lian; Sun, Zhiwei; Chen, Guang; Chen, Xuefeng; You, Jinmao; Wu, Yongning

2017-11-01

The intake of N-nitrosamines (NAs) from foodstuffs is considered to be an important influence factor for several cancers. But the rapid and sensitive screening of NAs remains a challenge in the field of food safety. Inspired by that, a sensitive and rapid method was demonstrated for determination of five NAs (Nitrosopyrrolidine, Nitrosodimethylamine, Nitrosodiethylamine, Nitrosodipropylamine and Nitrosodibutylamine) using dispersive liquid-liquid microextraction (DLLME) followed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The NAs were firstly denitrosated and labeled by 2-(11H-benzo[a]carbazol-11-yl) ethyl carbonochloridate (BCEC-Cl) and finally enriched by DLLME. Furthermore, the main DLLME conditions were optimized systematically. Under the optimal conditions, satisfactory limits of detection (LODs) were obtained with a range of 0.01-0.07ngg -1 , which were significantly lower than the reported methods. The developed method showed many merits including rapidity, simplicity, high sensitivity and excellent selectivity, which shows a broad prospect in food safety analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

How does the stimulus define exocytosis in adrenal chromaffin cells?

PubMed

Marengo, Fernando D; Cárdenas, Ana M

2018-01-01

The extent and type of hormones and active peptides secreted by the chromaffin cells of the adrenal medulla have to be adjusted to physiological requirements. The chromaffin cell secretory activity is controlled by the splanchnic nerve firing frequency, which goes from approximately 0.5 Hz in basal conditions to more than 15 Hz in stress. Thus, these neuroendocrine cells maintain a tonic release of catecholamines under resting conditions, massively discharge intravesicular transmitters in response to stress, or adequately respond to moderate stimuli. In order to adjust the secretory response to the stimulus, the adrenal chromaffin cells have an appropriate organization of Ca 2+ channels, secretory granules pools, and sets of proteins dedicated to selectively control different steps of the secretion process, such as the traffic, docking, priming and fusion of the chromaffin granules. Among the molecules implicated in such events are the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Ca 2+ sensors like Munc13 and synaptotagmin-1, chaperon proteins such as Munc18, and the actomyosin complex. In the present review, we discuss how these different actors contribute to the extent and maintenance of the stimulus-dependent exocytosis in the adrenal chromaffin cells.

Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

PubMed

Chevalier, Adrien S; Chaumont, François

2015-05-01

Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Analysis of the synaptotagmin family during reconstituted membrane fusion. Uncovering a class of inhibitory isoforms.

PubMed

Bhalla, Akhil; Chicka, Michael C; Chapman, Edwin R

2008-08-01

Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells is regulated by the Ca(2+)-binding protein synaptotagmin (syt) I. Sixteen additional isoforms of syt have been identified, but little is known concerning their biochemical or functional properties. Here, we assessed the abilities of fourteen syt isoforms to directly regulate SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor)-catalyzed membrane fusion. One group of isoforms stimulated neuronal SNARE-mediated fusion in response to Ca(2+), while another set inhibited SNARE catalyzed fusion in both the absence and presence of Ca(2+). Biochemical analysis revealed a strong correlation between the ability of syt isoforms to bind 1,2-dioleoyl phosphatidylserine (PS) and t-SNAREs in a Ca(2+)-promoted manner with their abilities to enhance fusion, further establishing PS and SNAREs as critical effectors for syt action. The ability of syt I to efficiently stimulate fusion was specific for certain SNARE pairs, suggesting that syts might contribute to the specificity of intracellular membrane fusion reactions. Finally, a subset of inhibitory syts down-regulated the ability of syt I to activate fusion, demonstrating that syt isoforms can modulate the function of each other.

Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

NASA Astrophysics Data System (ADS)

Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

2016-08-01

Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.

A Novel Role of MerC in Methylmercury Transport and Phytoremediation of Methylmercury Contamination.

PubMed

Sone, Yuka; Uraguchi, Shimpei; Takanezawa, Yasukazu; Nakamura, Ryosuke; Pan-Hou, Hidemitsu; Kiyono, Masako

2017-01-01

MerC, encoded by merC in the transposon Tn21 mer operon, is a heavy metal transporter with potential applications for phytoremediation of heavy metals such as mercuric ion and cadmium. In this study, we demonstrate that MerC also acts as a transporter for methylmercury. When MerC was expressed in Escherichia coli XL1-Blue, cells became hypersensitive to CH 3 Hg(I) and the uptake of CH 3 Hg(I) by these cells was higher than that by cells of the isogenic strain. Moreover, transgenic Arabidopsis plants expressing bacterial MerC or MerC fused to plant soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) accumulated CH 3 Hg(I) effectively and their growth was comparable to the wild-type plants. These results demonstrate that when the bacterium-derived merC gene is ectopically introduced in genetically modified plants, MerC expression in the transgenic plants promotes the transport and sequestration of methylmercury. Thus, our results show that the expression of merC in Arabidopsis results in transgenic plants that could be used for the phytoremediation and elimination of toxic methylmercury from the environment.

Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

PubMed Central

Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

2016-01-01

Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view. PMID:27493064

Factor Structure, Internal Consistency, and Screening Sensitivity of the GARS-2 in a Developmental Disabilities Sample

PubMed Central

Volker, Martin A.; Dua, Elissa H.; Lopata, Christopher; Thomeer, Marcus L.; Toomey, Jennifer A.; Smerbeck, Audrey M.; Rodgers, Jonathan D.; Popkin, Joshua R.; Nelson, Andrew T.; Lee, Gloria K.

2016-01-01

The Gilliam Autism Rating Scale-Second Edition (GARS-2) is a widely used screening instrument that assists in the identification and diagnosis of autism. The purpose of this study was to examine the factor structure, internal consistency, and screening sensitivity of the GARS-2 using ratings from special education teaching staff for a sample of 240 individuals with autism or other significant developmental disabilities. Exploratory factor analysis yielded a correlated three-factor solution similar to that found in 2005 by Lecavalier for the original GARS. Though the three factors appeared to be reasonably consistent with the intended constructs of the three GARS-2 subscales, the analysis indicated that more than a third of the GARS-2 items were assigned to the wrong subscale. Internal consistency estimates met or exceeded standards for screening and were generally higher than those in previous studies. Screening sensitivity was .65 and specificity was .81 for the Autism Index using a cut score of 85. Based on these findings, recommendations are made for instrument revision. PMID:26981279

General Factor of Personality Questionnaire (GFPQ): only one factor to understand personality?

PubMed

Amigó, Salvador; Caselles, Antonio; Micó, Joan C

2010-05-01

This study proposes a psychometric approach to assess the General Factor of Personality (GFP) to explain the whole personality. This approach defends the existence of one basic factor that represents the overall personality. The General Factor of Personality Questionnaire (GFPQ) is presented to measure the basic, combined trait of the complete personality. The questionnaire includes 20 items and is constituted by two scales with 10 items each one: the Extraversion Scale (ES) and the Introversion Scale (IS). The GFPQ shows adequate internal consistency and construct validity, while the relationships with the personality factors of other models and with psychopathology are as expected. It correlates positively and significantly with Extraversion (E) and Psychoticism (P), and negatively with Neuroticism (N) of Eysenck's EPQ (Eysenck Personality Questionnaire); it correlates positively and significantly with the Sensation Seeking Scaled (SSS) of Zuckerman, and is inside the expected direction with Sensitivity to Reward (SR) and Sensitivity to Punishment (SP) of the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), which represent the approach and avoidance trends of behavior, respectively. It not only relates negatively with the personality disorders of the anxiety spectrum, but also with the emotional disorders in relation to anxiety and depression, and it relates positively with the antisocial personality disorder.

Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy

PubMed Central

Kendziorra, Emil; Ahlborn, Kerstin; Spitzner, Melanie; Rave-Fränk, Margret; Emons, Georg; Gaedcke, Jochen; Kramer, Frank; Wolff, Hendrik A.; Becker, Heinz; Beissbarth, Tim; Ebner, Reinhard; Ghadimi, B.Michael; Pukrop, Tobias; Ried, Thomas; Grade, Marian

2011-01-01

A considerable percentage of rectal cancers are resistant to standard preoperative chemoradiotherapy. Because patients with a priori-resistant tumors do not benefit from multimodal treatment, understanding and overcoming this resistance remains of utmost clinical importance. We recently reported overexpression of the Wnt transcription factor TCF4, also known as TCF7L2, in rectal cancers that were resistant to 5-fluorouracil-based chemoradiotherapy. Because Wnt signaling has not been associated with treatment response, we aimed to investigate whether TCF4 mediates chemoradioresistance. RNA interference-mediated silencing of TCF4 was employed in three colorectal cancer (CRC) cell lines, and sensitivity to (chemo-) radiotherapy was assessed using a standard colony formation assay. Silencing of TCF4 caused a significant sensitization of CRC cells to clinically relevant doses of X-rays. This effect was restricted to tumor cells with high T cell factor (TCF) reporter activity, presumably in a β-catenin-independent manner. Radiosensitization was the consequence of (i) a transcriptional deregulation of Wnt/TCF4 target genes, (ii) a silencing-induced G2/M phase arrest, (iii) an impaired ability to adequately halt cell cycle progression after radiation and (iv) a compromised DNA double strand break repair as assessed by γH2AX staining. Taken together, our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance. Moreover, they suggest that TCF4 is a promising molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy. PMID:21983179

Inverting faces elicits sensitivity to race on the N170 component: a cross-cultural study.

PubMed

Vizioli, Luca; Foreman, Kay; Rousselet, Guillaume A; Caldara, Roberto

2010-01-29

Human beings are natural experts at processing faces, with some notable exceptions. Same-race faces are better recognized than other-race faces: the so-called other-race effect (ORE). Inverting faces impairs recognition more than for any other inverted visual object: the so-called face inversion effect (FIE). Interestingly, the FIE is stronger for same- compared to other-race faces. At the electrophysiological level, inverted faces elicit consistently delayed and often larger N170 compared to upright faces. However, whether the N170 component is sensitive to race is still a matter of ongoing debate. Here we investigated the N170 sensitivity to race in the framework of the FIE. We recorded EEG from Western Caucasian and East Asian observers while presented with Western Caucasian, East Asian and African American faces in upright and inverted orientations. To control for potential confounds in the EEG signal that might be evoked by the intrinsic and salient differences in the low-level properties of faces from different races, we normalized their amplitude-spectra, luminance and contrast. No differences on the N170 were observed for upright faces. Critically, inverted same-race faces lead to greater recognition impairment and elicited larger N170 amplitudes compared to inverted other-race faces. Our results indicate a finer-grained neural tuning for same-race faces at early stages of processing in both groups of observers.

Demographic factors associated with moral sensitivity among nursing students.

PubMed

Tuvesson, Hanna; Lützén, Kim

2017-11-01

Today's healthcare environment is often characterized by an ethically demanding work situation, and nursing students need to prepare to meet ethical challenges in their future role. Moral sensitivity is an important aspect of the ethical decision-making process, but little is known regarding nursing students' moral sensitivity and its possible development during nursing education. The aims of this study were to investigate moral sensitivity among nursing students, differences in moral sensitivity according to sample sub-group, and the relation between demographic characteristics of nursing students and moral sensitivity. A convenience sample of 299 nursing students from one university completed a questionnaire comprising questions about demographic information and the revised Moral Sensitivity Questionnaire. With the use of SPSS, non-parametric statistics, including logistic regression models, were used to investigate the relationship between demographic characteristics and moral sensitivity. Ethical considerations: The study followed the regulations according to the Swedish Ethical Review Act and was reviewed by the Ethics Committee of South-East Sweden. The findings showed that mean scores of nursing students' moral sensitivity were found in the middle to upper segment of the rating scale. Multivariate analysis showed that gender (odds ratio = 3.32), age (odds ratio = 2.09; 1.73), and parental status (odds ratio = 0.31) were of relevance to nursing students' moral sensitivity. Academic year was found to be unrelated to moral sensitivity. These demographic aspects should be considered when designing ethics education for nursing students. Future studies should continue to investigate moral sensitivity in nursing students, such as if and how various pedagogical strategies in ethics may contribute to moral sensitivity in nursing students.

The Factors Affecting the Intercultural Sensitivity Perception Level of Psychological Counseling and Guidance Students

ERIC Educational Resources Information Center

Tuncel, Ibrahim; Aricioglu, Ahu

2018-01-01

The purpose of this study is to determine the factors affecting the intercultural sensitivity perception levels of Psychological Counseling and Guidance students. This study was conducted in Pamukkale University which is located in the western part of Turkey. Data were gathered from 524 freshmen, sophomore, junior and senior students who are…

Photonic crystal nanofiber air-mode cavity with high Q-factor and high sensitivity for refractive index sensing

NASA Astrophysics Data System (ADS)

Ma, Xiaoxue; Chen, Xin; Nie, Hongrui; Yang, Daquan

2018-01-01

Recently, due to its superior characteristics and simple manufacture, such as small size, low loss, high sensitivity and convenience to couple, the optical fiber sensor has become one of the most promising sensors. In order to achieve the most effective realization of light propagation by changing the structure of sensors, FOM(S •Q/λres) ,which is determined by two significant variables Q-factor and sensitivity, as a trade-off parameter should be optimized to a high value. In typical sensors, a high Q can be achieved by confining the optical field in the high refractive index dielectric region to make an interaction between analytes and evanescent field of the resonant mode. However, the ignored sensitivity is relatively low with a high Q achieved, which means that the resonant wavelength shift changes non-obviously when the refractive index increases. Meanwhile, the sensitivity also leads to a less desirable FOM. Therefore, a gradient structure, which can enhance the performance of sensors by achieving high Q and high sensitivity, has been developed by Kim et al. later. Here, by introducing parabolic-tapered structure, the light field localized overlaps strongly and sufficiently with analytes. And based on a one-dimensional photonic-crystal nanofiber air-mode cavity, a creative optical fiber sensor is proposed by combining good stability and transmission characteristics of fiber and strengths of tapered structure, realizing excellent FOM {4.7 x 105 with high Q-factors (Q{106) and high sensitivities (<700 nm/RIU).

[Comparison of detection sensitivity in rapid-diagnosis influenza virus kits].

PubMed

Tokuno, Osamu; Fujiwara, Miki; Nakajoh, Yoshimi; Yamanouchi, Sumika; Adachi, Masayo; Ikeda, Akiko; Kitayama, Shigeo; Takahashi, Toshio; Kase, Tetsuo; Kinoshita, Shouhiro; Kumagai, Shunichi

2009-09-01

Rapid-diagnosis kits able to detect influenza A and B virus by immunochromatography developed by different manufacturers, while useful in early diagnosis, may vary widely in detection sensitivity. We compared sensitivity results for eight virus-detection kits in current use--Quick Chaser FluA, B (Mizuho Medy), Espline Influenza A & B-N (Fujirebio), Capilia Flu A + B (Nippon Beckton Dickinson & Alfesa Pharma), Poctem Influenza A/B (Otsuka Pharma & Sysmex), BD Flu Examan (Nippon Beckton Dickinson), Quick Ex-Flu "Seiken" (Denka Seiken), Quick Vue Rapid SP Influ (DP Pharma Biomedical), and Rapid Testa FLU stick (Daiichi Pure Chemicals)--against influenza virus stocks, contained five vaccination strains (one A/H1N1, two A/H3N2, and two B) and six clinical strains (two A/H1N1, two A/H3N2, and two B). Minimum detection concentrations giving immunologically positive signals in serial dilution and RNA copies in positive dilution in real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were assayed for all kits and virus stock combinations. RNA log10 copy numbers/mL in dilutions within detection limits yielded 5.68-7.02, 6.37-7,17, and 6.5-8.13 for A/H1N1, A/H3N2, and B. Statistically significant differences in sensitivity were observed between some kit combinations. Detection sensitivity tended to be relatively higher for influenza A than B virus. This is assumed due to different principles in kit methods, such as monoclonal antibodies, specimen-extraction conditions, and other unknown factors.

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Enhanced depigmenting effects of N-glycosylation inhibitors delivered by pH-sensitive liposomes into HM3KO melanoma cells.

PubMed

Park, Ju Young; Choi, Hyunjung; Hwang, Jae Sung; Kim, Junoh; Chang, Ih-Seop

2008-01-01

Delivery activity of pH-sensitive 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE):cholesteryl hemisuccinate (CHEMS) liposomes was assessed as an in vitro intracellular carrier system to increase the bioavailability of depigmentation actives. N-glycosylation inhibitors have a glycosylation-inhibiting effect, which is useful for the skin depigmentation that operates by interfering with the maturation of tyrosinase. However, an N-glycosylation inhibitor does not easily pass through skin or even cellular membranes due to its water-soluble property. Therefore, it should be transported to target cells by an efficient delivery carrier to reduce the glycosylated tyrosinase. Glycosylation-inhibiting and depigmentation effects of N-butyldeoxynojirimycine (NB-DNJ) and 1-deoxynojirimycine (DNJ)-loaded liposomes were evaluated using Western blotting and measurement of synthesized melanin. Interestingly, it was found that the pH-sensitive liposomes increased the glycosylation-inhibiting and thus, pigment-lightening effects of N-glycosylation inhibitors in vitro. In addition, cargo materials loaded in pH-sensitive liposomes were found to be much more efficiently delivered into the cytoplasm, as observed in fluorescent-activated cell sorting (FACS) and confocal laser-scanning microscopic (CLSM) analysis. These results indicate that pH-sensitive DOPE:CHEMS liposomes have a strong potential as a carrier system to promote delivery efficiency and to enhance the biological effects of water-soluble actives for applications in cosmetics, personal care products, and pharmaceutics.

Experiential avoidance as a moderator of the relationship between anxiety sensitivity and perceived stress.

PubMed

Bardeen, Joseph R; Fergus, Thomas A; Orcutt, Holly K

2013-09-01

Given the significant deleterious effects of stress on psychological and physical well-being, the present two-part study sought to clarify relations among putative vulnerability factors (i.e., anxiety sensitivity, experiential avoidance) for perceived stress. Relations among anxiety sensitivity, experiential avoidance, and perceived stress were examined using a large college student sample (N=400) in Study 1 and were replicated using a large community sample (N=838) in Study 2. As predicted, experiential avoidance moderated the relationship between anxiety sensitivity and perceived stress. Contrary to expectations, simple effects in both studies revealed that anxiety sensitivity shared a significant positive association with perceived stress at low, but not high, levels of experiential avoidance. The moderating role of experiential avoidance was found to be robust to the effects of general distress. Moreover, anxiety sensitivity and experiential avoidance evidenced a differential pattern of relations with perceived stress than was evidenced with related negative affective states (i.e., anxiety and depression). The present results suggest that experiential avoidance appears to be a vulnerability factor of particular importance for understanding the phenomenology of perceived stress. Conceptual and clinical implications are discussed. Copyright © 2013. Published by Elsevier Ltd.

Common Risk Factors for Urinary House Soiling (Periuria) in Cats and Its Differentiation: The Sensitivity and Specificity of Common Diagnostic Signs

PubMed Central

Barcelos, Ana Maria; McPeake, Kevin; Affenzeller, Nadja; Mills, Daniel Simon

2018-01-01

Urinary house soiling (periuria) in the home is a common but serious behaviour problem in cats. Although many specific risk factors and triggers have been postulated, their importance is largely unknown. This study assessed: (1) the significance of purported risk factors for periuria as well as specifically marking and latrine behaviour in the home; (2) the specificity and sensitivity of signs commonly used to differentiate latrine and marking behaviour. Owner responses to an internet survey (n = 245) were classified into three groups: control, marking and latrine behaviour, along with 41 potential risk factors and 15 predictors used to diagnose marking and latrine problems. Univariate statistical analyses and non-parametric tests of association were used to determine simple associations. In addition the sensitivity and specificity of four cardinal signs (posture to urinate, attempt to cover soiled area, surface chosen and volume of urine deposited) were calculated. Significant potential risk factors were: age (marking cats were older than the other two groups); multi-cat household (increased risk of marking and latrine behaviours); free outside access and cat flaps in the house (higher frequency of marking); outside access in general (lower prevalence of latrine behaviour); defecation outside the litter box (higher frequency of latrine behaviour); a heavy dependence by the cat on its owner (lower frequency of latrine behaviour) and a relaxed personality (lower risk of marking behaviour). Litterbox attributes and disease related factors were not significant. Individual cardinal signs were generally not good predictors of diagnosis. This study challenges the poor quality of evidence that has underpinned some of the hypotheses concerning the causes of periuria in cats. The results, in particular, highlight the general importance of the social environment, with the presence of other cats in the household, the cat-owner bond and personality related factors

Temperament as a modulating factor of pain sensitivity in combat sport athletes.

PubMed

Leźnicka, Katarzyna; Starkowska, Anna; Tomczak, Maciej; Cięszczyk, Paweł; Białecka, Monika; Ligocka, Maria; Żmijewski, Piotr; Pawlak, Maciej

2017-10-15

The aim of this study was to characterise the temperament of combat athletes in comparison to that of individuals who do not practise any sports with regard to pain sensitivity measured with the cold pressor test (CPT) and pressure pain threshold (PPT). The study involved 284 healthy men, aged 18 to 43years. The first group consisted of 198 combat athletes, including boxing (n=19), mixed martial arts (MMA) (n=97) and karate (n=82), aged from 18 to 43years. The control group consisted of 86 subjects between the ages of 18 and 26years, academic students not practising any sport professionally. Pain threshold and pain tolerance were evaluated using the CPT and a pressure algometer. Temperament was measured with the Formal Characteristics of Behaviour - Temperament Inventory (FCB-TI). The contact athletes showed much higher tolerance to pain than the control group using both tools: CPT (p=0.007) and PPT (p<0.001). In athletes, but not in controls, relationships were noted between BMI and endurance (r=0.20; p=0.004), BMI and activity (r=-0.283; p<0.001), BMI and pain threshold (r=0.15; p<0.05), and BMI and pain tolerance (r=0.30; p<0.001), when measured by the algometer - this necessitating adjustment for further analysis. The athletes and students in the study groups differed significantly with regard to intensity of four temperamental traits, but after BMI adjustments only group differences in Preservation, Sensory sensitivity and Emotional reactivity remained significant'. These differences indicate individual differences in perception and reaction to external stimuli. Significantly higher pain tolerance (CPT and PPT) in the athletes studied was related to specific psychological features. The obtained results of temperamental characteristics may indicate higher resilience of the nervous system in combat athletes in comparison to non-athletes. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural face encoding: How task affects the N170's sensitivity to race.

PubMed

Senholzi, Keith B; Ito, Tiffany A

2013-12-01

The N170 event-related potential (ERP) component differentiates faces from non-faces, but studies aimed at investigating whether the processing indexed by this component is also sensitive to racial differences among faces have garnered conflicting results. Here, we explore how task affects the influence of race on the N170 among White participants. N170s were larger to ingroup White faces than outgroup Black faces, but only for those required to attend to race, suggesting that attention to race can result in deeper levels of processing for ingroup members. Conversely, N170s were larger to Black faces than White faces for participants who attended to the unique identity of the faces, suggesting that attention to identity can result in preferential recruitment of cognitive resources for outgroup members. Taken together, these findings suggest that race can differentially impact face processing at early stages of encoding, but differences in processing are contingent upon one's goal state.

Hearing impairment, cognition and speech understanding: exploratory factor analyses of a comprehensive test battery for a group of hearing aid users, the n200 study.

PubMed

Rönnberg, Jerker; Lunner, Thomas; Ng, Elaine Hoi Ning; Lidestam, Björn; Zekveld, Adriana Agatha; Sörqvist, Patrik; Lyxell, Björn; Träff, Ulf; Yumba, Wycliffe; Classon, Elisabet; Hällgren, Mathias; Larsby, Birgitta; Signoret, Carine; Pichora-Fuller, M Kathleen; Rudner, Mary; Danielsson, Henrik; Stenfelt, Stefan

2016-11-01

The aims of the current n200 study were to assess the structural relations between three classes of test variables (i.e. HEARING, COGNITION and aided speech-in-noise OUTCOMES) and to describe the theoretical implications of these relations for the Ease of Language Understanding (ELU) model. Participants were 200 hard-of-hearing hearing-aid users, with a mean age of 60.8 years. Forty-three percent were females and the mean hearing threshold in the better ear was 37.4 dB HL. LEVEL1 factor analyses extracted one factor per test and/or cognitive function based on a priori conceptualizations. The more abstract LEVEL 2 factor analyses were performed separately for the three classes of test variables. The HEARING test variables resulted in two LEVEL 2 factors, which we labelled SENSITIVITY and TEMPORAL FINE STRUCTURE; the COGNITIVE variables in one COGNITION factor only, and OUTCOMES in two factors, NO CONTEXT and CONTEXT. COGNITION predicted the NO CONTEXT factor to a stronger extent than the CONTEXT outcome factor. TEMPORAL FINE STRUCTURE and SENSITIVITY were associated with COGNITION and all three contributed significantly and independently to especially the NO CONTEXT outcome scores (R(2) = 0.40). All LEVEL 2 factors are important theoretically as well as for clinical assessment.

Species Origin of Genomic Factors in Nicotiana nudicaulis Watson Controlling Hybrid Lethality in Interspecific Hybrids between N. nudicaulis Watson and N. tabacum L

PubMed Central

Liu, Hongshuo; Marubashi, Wataru

2014-01-01

Hybrid lethality is expressed at 28°C in the cross Nicotiana nudicaulis×N. tabacum. The S subgenome of N. tabacum has been identified as controlling this hybrid lethality. To clarify the responsible genomic factor(s) of N. nudicaulis, we crossed N. trigonophylla (paternal progenitor of N. nudicaulis) with N. tabacum, because hybrids between N. sylvestris (maternal progenitor of N. nudicaulis) and N. tabacum are viable when grown in a greenhouse. In the cross N. trigonophylla×N. tabacum, approximately 50% of hybrids were vitrified, 20% were viable, and 20% were nonviable at 28°C. To reveal which subgenome of N. tabacum was responsible for these phenotypes, we crossed N. trigonophylla with two progenitors of N. tabacum, N. sylvestris (SS) and N. tomentosiformis (TT). In the cross N. sylvestris×N. trigonophylla, we confirmed that over half of hybrids of N. sylvestris×N. trigonophylla were vitrified, and none of the hybrids of N. trigonophylla×N. tomentosiformis were. The results imply that the S subgenome, encoding a gene or genes inducing hybrid lethality in the cross between N. nudicaulis and N. tabacum, has one or more genomic factors that induce vitrification. Furthermore, in vitrified hybrids of N. trigonophylla×N. tabacum and N. sylvestris×N. trigonophylla, we found that nuclear fragmentation, which progresses during expression of hybrid lethality, was accompanied by vitrification. This observation suggests that vitrification has a relationship to hybrid lethality. Based on these results, we speculate that when N. nudicaulis was formed approximately 5 million years ago, several causative genomic factors determining phenotypes of hybrid seedlings were inherited from N. trigonophylla. Subsequently, genome downsizing and various recombination-based processes took place. Some of the causative genomic factors were lost and some became genomic factor(s) controlling hybrid lethality in extant N. nudicaulis. PMID:24806486

High sensitivity of Franz-Keldysh oscillations in photoreflectance spectra for probing morphology in Al{x}Ga{1-{x}}N/GaN heterostructures

NASA Astrophysics Data System (ADS)

Takeuchi, H.; Yamamoto, Y.; Kamo, Y.; Kunii, T.; Oku, T.; Wakaiki, S.; Nakayama, M.

2007-02-01

We demonstrate that Franz-Keldysh oscillations (FKOs) observed by photoreflectance (PR) spectroscopy are highly sensitive to the surface morphology of Al{x}Ga{1-x}N layers in Al{x}Ga{1-x}N heterostructures. Three Al{0.2}Ga{0.8}N/GaN heterostructures with different surface-morphology profiles, which are confirmed with atomic force microscopy, have been investigated. The X-ray-diffraction patterns are hardly affected by the Al{0.2}Ga{0.8}N/GaN-layer morphology. In contrast, it is revealed that cracks and pits dominating the morphology remarkably reduce the amplitude of the FKOs from the Al{0.2}Ga{0.8}N/GaN layer, which is attributed to the following two mechanisms related to the cracks and pits. One is lifetime broadening due to carrier scattering, and the other is the suppression of the modulation magnitude for the built-in electric field, which is caused by the trapping and recombination of photogenerated carriers at the surface.

The brief negative symptom scale (BNSS): Sensitivity to treatment effects.

PubMed

Kirkpatrick, Brian; Saoud, Jay B; Strauss, Gregory P; Ahmed, Anthony O; Tatsumi, Kazunori; Opler, Mark; Luthringer, Remy; Davidson, Michael

2017-12-21

The Brief Negative Symptom Scale (BNSS) grew out of a recommendation by the NIMH-sponsored Consensus Development Conference on Negative Symptoms that a scale based on contemporary concepts be developed. We assessed sensitivity to change of the BNSS in a trial of MIN-101, which showed efficacy for negative symptoms (PANSS pentagonal model) at daily doses of 32 and 64mg/day. Using mixed-effects model for repeated measures, we examined change in BNSS total score and in the BNSS factors of anhedonia/avolition/asociality (AAA), and expressivity (EXP). Compared to placebo, the 64mg group (N=83) showed a significant decrease in BNSS total score (effect size d [ES] 0.56, p<0.01) and both factor scores (AAA ES=0.48, EXP ES=0.46, p<0.02 for both). Patients in the trial had minimal depression and positive symptom scores; covarying for disorganization, positive symptoms, or anxiety/depression did not cause a meaningful change in the significance of the BNSS total or factor scores in this group. The 32mg group (N=78) did not differ significantly from placebo (N=83) on BNSS total score (ES=0.33, p<0.09), AAA (ES=0.25, p<0.20) or EXP (ES=0.30, p<0.12) scores. These results demonstrate the BNSS is sensitive to change. Copyright © 2017. Published by Elsevier B.V.

Anxiety sensitivity among Cambodian refugees with panic disorder: A factor analytic investigation.

PubMed

Hinton, Devon E; Pich, Vuth; Safren, Steven A; Pollack, Mark H; McNally, Richard J

2006-01-01

Among Cambodian refugees with panic disorder (N = 208), we performed two factor analyses, one with the ASI, another with an Augmented ASI (consisting of the 16-item ASI supplemented with a 9-item addendum that assesses additional Cambodian concerns about anxiety-related sensations). The principal component analysis of the ASI yielded a 3-factor solution (I, "Weak Heart Concerns"; II, "Social Concerns"; III, "Control Concerns"); the Augmented ASI, a 4-factor solution: I, "Wind Attack Concerns"; II, "Weak Heart Concerns"; III, "Social Concerns"; and IV, "Control Concerns." The item clustering within the factor solution of both the ASI and Augmented ASI illustrates the role of cultural syndromes in generating fear of mental and bodily events.

The importance of geomorphic and hydrologic factors in shaping the sensitivity of alpine/subalpine lake volumes to shifts in climate

NASA Astrophysics Data System (ADS)

Mercer, J.; Liefert, D. T.; Shuman, B. N.; Befus, K. M.; Williams, D. G.; Kraushaar, B.

2017-12-01

Alpine and subalpine lakes are important components of the hydrologic cycle in mountain ecosystems. These lakes are also highly sensitive to small shifts in temperature and precipitation. Mountain lake volumes and their contributions to mountain hydrology may change in response to even minor declines in snowpack or increases in temperature. However, it is still not clear to what degree non-climatic factors, such as geomorphic setting and lake geometry, play in shaping the sensitivity of high elevation lakes to climate change. We investigated the importance of lake geometry and groundwater connectivity to mountain lakes in the Snowy Range, Wyoming using a combination of hydrophysical and hydrochemical methods, including stable water isotopes, to better understand the role these factors play in controlling lake volume. Water isotope values in open lakes were less sensitive to evaporation compared to those in closed basin lakes. Lake geometry played an important role, with wider, shallower lakes being more sensitive to evaporation over time. Groundwater contributions appear to play only a minor role in buffering volumetric changes to lakes over the growing season. These results confirm that mountain lakes are sensitive to climate factors, but also highlight a significant amount of variability in that sensitivity. This research has implications for water resource managers concerned with downstream water quantity and quality from mountain ecosystems, biologists interested in maintaining aquatic biodiversity, and paleoclimatologists interested in using lake sedimentary information to infer past climate regimes.

Prognostic Factors for Hormone Sensitive Metastatic Prostate Cancer: Impact of Disease Volume

PubMed

Alhanafy, Alshimaa Mahmoud; Zanaty, Fouad; Ibrahem, Reda; Omar, Suzan

2018-04-27

Background and Aim: The optimal management of metastatic hormone-sensitive prostate cancer has been controversial in recent years with introduction of upfront chemohormonal treatment based on results of several Western studies. This changing landscape has renewed interest in the concept “disease volume”, the focus of the present study is the Egyptian patients. Methods: Patients with hormone sensitive metastatic prostate cancer presenting at Menoufia University Hospital, Egypt, during the period from June 2013 to May 2016, were enrolled. All received hormonal treatment. Radiologic images were evaluated and patients were stratified according to their disease volume into high or low, other clinical and pathological data that could affect survival also being collected and analyzed. Results: A total of 128 patients were included, with a median age of 70 years (53.9% ≥70). About 46% had co-morbidities, 62% having high volume disease. During the median follow up period of 28 months about half of the patients progressed and one third received chemotherapy. On univariate analysis, disease volume, performance status (PS), prostate specific antigen level (PSA) and presence of pain at presentation were identified as factors influencing overall survival. Multivariate analysis revealed the independent predictor factors for survival to be PS, PSA and disease volume. The median overall survival with 27 months was high volume versus 49 with low volume disease (hazard ratio 2.1; 95% CI 1.2 - 4.4; P=0.02). Median progression free survival was 19 months in the high volume, as compared with 48 months in the low volume disease patients (hazard ratio, 2.44; 95% CI, 1.42 – 7.4; P=0.009). Conclusions: Disease volume is a reliable predictor of survival which should be incorporated with other important factors as; patient performance status and comorbidities in treatment decision-making. Creative Commons Attribution License

Photoluminescence-excitation spectroscopy as a highly sensitive probe for carrier transport processes affected by surface damages in AlxGa1-xN/GaN heterostructures

NASA Astrophysics Data System (ADS)

Takeuchi, Hideo; Yamamoto, Yoshitsugu; Kamo, Yoshitaka; Kunii, Tetsuo; Oku, Tomoki; Shirahama, Takeo; Tanaka, Hiroyasu; Nakayama, Masaaki

2007-08-01

We demonstrate that photoluminescence-excitation (PLE) spectroscopy can probe with high sensitivity the effects of plasma-induced surface damages on photogenerated-carrier-transport processes in AlxGa1-xN/GaN heterostructures, on the basis of systematic optical and structural characterization results for the as-grown reference sample and the plasma-exposed sample. It is found from the structural characterizations with atomic force microscopy that the plasma exposure remarkably modifies the atomic step boundaries and the pits on the AlxGa1-xN surface, which leads to a remarkable difference between the PLE spectra of the bound exciton photoluminescence from the underlying GaN layer in the two samples. The PLE spectrum of the reference sample shows a step rising from the AlxGa1-xN fundamental transition energy toward the high energy side, whereas the rising step disappears in the PLE spectrum of the plasma-exposed sample. In contrast, the reflectance characteristics are the same in the two samples; i.e., the excitonic transition itself is not influenced by the plasma exposure. The present findings indicate that the PLE spectral profile is sensitive to the change in efficiency of the photogenerated carrier injection from the AlxGa1-xN layer to the GaN layer. Thus, it is concluded that the PLE characterization is effective to probe the photogenerated-carrier transport in heterostructures.

Energetics and Kinetics of trans-SNARE Zippering

NASA Astrophysics Data System (ADS)

Rebane, Aleksander A.; Shu, Tong; Krishnakumar, Shyam; Rothman, James E.; Zhang, Yongli

Synaptic exocytosis relies on assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins into a four-helix bundle to drive membrane fusion. Complementary SNAREs anchored to the synaptic vesicle (v-SNARE) and the plasma membrane (t-SNARE) associate from their N-termini, transiting a half-assembled intermediate (trans-SNARE), and ending at their C-termini with a rapid power stroke that leads to membrane fusion. Although cytosolic SNARE assembly has been characterized, it remains unknown how membranes modulate the energetics and kinetics of SNARE assembly. Here, we present optical tweezers measurements on folding of single membrane proteins in phospholipid bilayers. To our knowledge, this is the first such report. We measured the energetics, kinetics, and assembly intermediates of trans-SNAREs formed between a t-SNARE inserted into a bead-supported bilayer and a v-SNARE in a nanodisc. We found that the repulsive force of the apposed membranes increases the lifetime of the half-assembled intermediate. Our findings provide a single-molecule platform to study the regulation of trans-SNARE assembly by proteins that act on the half-assembled state, and thus reveal the mechanistic basis of the speed and high fidelity of synaptic transmission. This work was supported by US National Institutes of Health Grants F31 GM119312-01 (to A.A.R) and R01 GM093341 (to Y.Z.).

High sensitivity and high Q-factor nanoslotted parallel quadrabeam photonic crystal cavity for real-time and label-free sensing

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

Yang, Daquan; State Key Laboratory of Information Photonics and Optical Communications, School of Information and Communication Engineering, Beijing University of Posts and Telecommunications, Beijing 100876; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138

We experimentally demonstrate a label-free sensor based on nanoslotted parallel quadrabeam photonic crystal cavity (NPQC). The NPQC possesses both high sensitivity and high Q-factor. We achieved sensitivity (S) of 451 nm/refractive index unit and Q-factor >7000 in water at telecom wavelength range, featuring a sensor figure of merit >2000, an order of magnitude improvement over the previous photonic crystal sensors. In addition, we measured the streptavidin-biotin binding affinity and detected 10 ag/mL concentrated streptavidin in the phosphate buffered saline solution.

Increasing the availability of l-arginine and nitric oxide increases sensitivity of nitrous oxide (N2O)-insensitive inbred mice to N2O-induced antinociception.

PubMed

Chung, Eunhee; Ohgami, Yusuke; Quock, Raymond M

2016-07-01

Nitrous oxide (N2O)-induced antinociception in mice is dependent on the neuromodulator nitric oxide (NO). In contrast to C57BL/6J (B6) mice, DBA/2J (D2) mice fail to respond to N2O with a robust antinociceptive response or with an increase in brain nitric oxide synthase (NOS) enzyme activity, suggesting that failure of D2 mice to respond to N2O might result from a deficit of NO function. Therefore, it was of interest to determine whether increasing the availability of NO might increase sensitivity of D2 mice to N2O. Male D2 mice were pretreated with sub-antinociceptive intracerebroventricular doses of the NO donor 3-morpholinosydnoimine or the NO precursor l-arginine then assessed for responsiveness to N2O-induced antinociception using the acetic acid abdominal constriction test. Both pretreatments increased the antinociceptive responsiveness of D2 mice to N2O. These results indicate that the NOS enzyme in D2 mice is functional and that the deficit in NO function that obstructs sensitivity to N2O-induced antinociception may lie in availability or utilization of l-arginine. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of Chinese women with primary ovarian insufficiency by high resolution array-comparative genomic hybridization.

PubMed

Liao, Can; Fu, Fang; Yang, Xin; Sun, Yi-Min; Li, Dong-Zhi

2011-06-01

Primary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years. The etiology of primary ovarian insufficiency in human female patients is still unclear. The purpose of this study is to investigate the potential genetic causes in primary amenorrhea patients by high resolution array based comparative genomic hybridization (array-CGH) analysis. Following the standard karyotyping analysis, genomic DNA from whole blood of 15 primary amenorrhea patients and 15 normal control women was hybridized with Affymetrix cytogenetic 2.7M arrays following the standard protocol. Copy number variations identified by array-CGH were confirmed by real time polymerase chain reaction. All the 30 samples were negative by conventional karyotyping analysis. Microdeletions on chromosome 17q21.31-q21.32 with approximately 1.3 Mb were identified in four patients by high resolution array-CGH analysis. This included the female reproductive secretory pathway related factor N-ethylmaleimide-sensitive factor (NSF) gene. The results of the present study suggest that there may be critical regions regulating primary ovarian insufficiency in women with a 17q21.31-q21.32 microdeletion. This effect might be due to the loss of function of the NSF gene/genes within the deleted region or to effects on contiguous genes.

Discrete, continuous, and stochastic models of protein sorting in the Golgi apparatus

PubMed Central

Gong, Haijun; Guo, Yusong; Linstedt, Adam

2017-01-01

The Golgi apparatus plays a central role in processing and sorting proteins and lipids in eukaryotic cells. Golgi compartments constantly exchange material with each other and with other cellular components, allowing them to maintain and reform distinct identities despite dramatic changes in structure and size during cell division, development, and osmotic stress. We have developed three minimal models of membrane and protein exchange in the Golgi—a discrete, stochastic model, a continuous ordinary differential equation model, and a continuous stochastic differential equation model—each based on two fundamental mechanisms: vesicle-coat-mediated selective concentration of cargoes and soluble N-ethylmaleimide-sensitive factor attachment protein receptor SNARE proteins during vesicle formation and SNARE-mediated selective fusion of vesicles. By exploring where the models differ, we hope to discover whether the discrete, stochastic nature of vesicle-mediated transport is likely to have appreciable functional consequences for the Golgi. All three models show similar ability to restore and maintain distinct identities over broad parameter ranges. They diverge, however, in conditions corresponding to collapse and reassembly of the Golgi. The results suggest that a continuum model provides a good description of Golgi maintenance but that considering the discrete nature of vesicle-based traffic is important to understanding assembly and disassembly of the Golgi. Experimental analysis validates a prediction of the models that altering guanine nucleotide exchange factor expression levels will modulate Golgi size. PMID:20365406

UNC-18 Promotes Both the Anterograde Trafficking and Synaptic Function of Syntaxin

PubMed Central

McEwen, Jason M.

2008-01-01

The SM protein UNC-18 has been proposed to regulate several aspects of secretion, including synaptic vesicle docking, priming, and fusion. Here, we show that UNC-18 has a chaperone function in neurons, promoting anterograde transport of the plasma membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein Syntaxin-1. In unc-18 mutants, UNC-64 (Caenorhabditis elegans Syntaxin-1) accumulates in neuronal cell bodies. Colocalization studies and analysis of carbohydrate modifications both suggest that this accumulation occurs in the endoplasmic reticulum. This trafficking defect is specific for UNC-64 Syntaxin-1, because 14 other SNARE proteins and two active zone markers were unaffected. UNC-18 binds to Syntaxin through at least two mechanisms: binding to closed Syntaxin, or to the N terminus of Syntaxin. It is unclear which of these binding modes mediates UNC-18 function in neurons. The chaperone function of UNC-18 was eliminated in double mutants predicted to disrupt both modes of Syntaxin binding, but it was unaffected in single mutants. By contrast, mutations predicted to disrupt UNC-18 binding to the N terminus of Syntaxin caused significant defects in locomotion behavior and responsiveness to cholinesterase inhibitors. Collectively, these results demonstrate the UNC-18 acts as a molecular chaperone for Syntaxin transport in neurons and that the two modes of UNC-18 binding to Syntaxin are involved in different aspects of UNC-18 function. PMID:18596236

Carrier transport and sensitivity issues in heterojunction with intrinsic thin layer solar cells on N-type crystalline silicon: A computer simulation study

NASA Astrophysics Data System (ADS)

Rahmouni, M.; Datta, A.; Chatterjee, P.; Damon-Lacoste, J.; Ballif, C.; Roca i Cabarrocas, P.

2010-03-01

Heterojunction with intrinsic thin layer or "HIT" solar cells are considered favorable for large-scale manufacturing of solar modules, as they combine the high efficiency of crystalline silicon (c-Si) solar cells, with the low cost of amorphous silicon technology. In this article, based on experimental data published by Sanyo, we simulate the performance of a series of HIT cells on N-type crystalline silicon substrates with hydrogenated amorphous silicon (a-Si:H) emitter layers, to gain insight into carrier transport and the general functioning of these devices. Both single and double HIT structures are modeled, beginning with the initial Sanyo cells having low open circuit voltages but high fill factors, right up to double HIT cells exhibiting record values for both parameters. The one-dimensional numerical modeling program "Amorphous Semiconductor Device Modeling Program" has been used for this purpose. We show that the simulations can correctly reproduce the electrical characteristics and temperature dependence for a set of devices with varying I-layer thickness. Under standard AM1.5 illumination, we show that the transport is dominated by the diffusion mechanism, similar to conventional P/N homojunction solar cells, and tunneling is not required to describe the performance of state-of-the art devices. Also modeling has been used to study the sensitivity of N-c-Si HIT solar cell performance to various parameters. We find that the solar cell output is particularly sensitive to the defect states on the surface of the c-Si wafer facing the emitter, to the indium tin oxide/P-a-Si:H front contact barrier height and to the band gap and activation energy of the P-a-Si:H emitter, while the I-a-Si:H layer is necessary to achieve both high Voc and fill factor, as it passivates the defects on the surface of the c-Si wafer. Finally, we describe in detail for most parameters how they affect current transport and cell properties.

The application of Global Sensitivity Analysis to quantify the dominant input factors for hydraulic model simulations

NASA Astrophysics Data System (ADS)

Savage, James; Pianosi, Francesca; Bates, Paul; Freer, Jim; Wagener, Thorsten

2015-04-01

Predicting flood inundation extents using hydraulic models is subject to a number of critical uncertainties. For a specific event, these uncertainties are known to have a large influence on model outputs and any subsequent analyses made by risk managers. Hydraulic modellers often approach such problems by applying uncertainty analysis techniques such as the Generalised Likelihood Uncertainty Estimation (GLUE) methodology. However, these methods do not allow one to attribute which source of uncertainty has the most influence on the various model outputs that inform flood risk decision making. Another issue facing modellers is the amount of computational resource that is available to spend on modelling flood inundations that are 'fit for purpose' to the modelling objectives. Therefore a balance needs to be struck between computation time, realism and spatial resolution, and effectively characterising the uncertainty spread of predictions (for example from boundary conditions and model parameterisations). However, it is not fully understood how much of an impact each factor has on model performance, for example how much influence changing the spatial resolution of a model has on inundation predictions in comparison to other uncertainties inherent in the modelling process. Furthermore, when resampling fine scale topographic data in the form of a Digital Elevation Model (DEM) to coarser resolutions, there are a number of possible coarser DEMs that can be produced. Deciding which DEM is then chosen to represent the surface elevations in the model could also influence model performance. In this study we model a flood event using the hydraulic model LISFLOOD-FP and apply Sobol' Sensitivity Analysis to estimate which input factor, among the uncertainty in model boundary conditions, uncertain model parameters, the spatial resolution of the DEM and the choice of resampled DEM, have the most influence on a range of model outputs. These outputs include whole domain maximum

Nitrous oxide emission factors from N-fertilizer in sugarcane production in Brazil

NASA Astrophysics Data System (ADS)

Galdos, M. V.; Siqueira Neto, M.; Feigl, B. J.; Carvalho, J. L.; Cerri, C. E.; Cerri, C. C.

2013-12-01

The Brazilian sugarcane production is rapidly expanding due to the increase of global demand for ethanol. Concurrently the necessary inputs to culture, especially N-fertilizer, are growing, since N is one of the key element to maintain sugarcane productivity. However, it is known that N-fertilizer is responsible for the largest share of N2O emissions from agricultural soils. The Intergovernmental Panel on Climate Changes (IPCC) estimated that under favorable climatic conditions approximately 1% of the N-fertilizer applied can be emitted as N2O. Our goal was to estimate N2O emission factors from N-fertilizer used in the sugarcane ratoon for ethanol production. A field study was conducted at the Capuava Mill, located in southeastern Brazil. The experimental design was completely randomized, with four replications in a factorial scheme (2 x 2): two N sources (urea and ammonium nitrate), two application rates (80 and 120 kg ha-1), and a control treatment. N2O concentrations were determined by gas chromatography using a Shimadzu© GC-mini. N2O fluxes were calculated from linear regressions of concentration versus incubation time in the soil static chambers. The N2O emission factor of N-fertilizer was calculated according to the methodology described in the Guidelines for National Greenhouse Gas Inventories (IPCC). Comparatively, ammonium nitrate emitted 45 to 75% less N2O than urea application. There was no significant difference in N2O emission between the two applied rates of urea. Also the N2O emission factor of ammonium nitrate (0.3×0.2%) was lower than that of urea (1.1×0.4%). Our results indicated that on average the N fertilization of sugarcane plantation has an emission factor of 0.7×0.5% suggesting that N-fertilizer management can be used to reduce greenhouse gas emissions in order to improve the sustainability of bioethanol from sugarcane.

Improvement of insulin sensitivity in response to exercise training in type 2 diabetes mellitus is associated with vascular endothelial growth factor A expression.

PubMed

Wagner, Henrik; Fischer, Helene; Degerblad, Marie; Alvarsson, Michael; Gustafsson, Thomas

2016-09-01

Insulin sensitivity changes in response to exercise training demonstrate a large variation. Vascular endothelial growth factor A could promote increased insulin sensitivity through angiogenesis. We investigated associations between changes in expression of key genes and insulin sensitivity, aerobic capacity and glycaemic control following exercise training in diabetes mellitus type 2. Subjects with diabetes mellitus type 2 underwent 12 weeks of structured exercise. Euglycaemic clamp, exercise test and HbA1c were performed. Muscle biopsies were obtained for mRNA expression. A total of 16 subjects completed the study. Change in vascular endothelial growth factor A expression was positively associated with an increase in insulin sensitivity (p = 0.004) and with a decrease in HbA1c (p = 0.034). Vascular endothelial growth factor A receptor-1 expression showed similar associations. The variation in physical adaptation to exercise training in diabetes mellitus type 2 was associated with changes in expression of vascular endothelial growth factor A in muscle. This difference in induced gene expression could contribute to the variation in exercise training effects on insulin sensitivity. Measures of capillary blood flow need to be assessed in future studies. © The Author(s) 2016.

N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.

PubMed

Stamler, J; Mendelsohn, M E; Amarante, P; Smick, D; Andon, N; Davies, P F; Cooke, J P; Loscalzo, J

1989-09-01

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.

Dandelions, tulips and orchids: evidence for the existence of low-sensitive, medium-sensitive and high-sensitive individuals.

PubMed

Lionetti, Francesca; Aron, Arthur; Aron, Elaine N; Burns, G Leonard; Jagiellowicz, Jadzia; Pluess, Michael

2018-01-22

According to empirical studies and recent theories, people differ substantially in their reactivity or sensitivity to environmental influences with some being generally more affected than others. More sensitive individuals have been described as orchids and less-sensitive ones as dandelions. Applying a data-driven approach, we explored the existence of sensitivity groups in a sample of 906 adults who completed the highly sensitive person (HSP) scale. According to factor analyses, the HSP scale reflects a bifactor model with a general sensitivity factor. In contrast to prevailing theories, latent class analyses consistently suggested the existence of three rather than two groups. While we were able to identify a highly sensitive (orchids, 31%) and a low-sensitive group (dandelions, 29%), we also detected a third group (40%) characterised by medium sensitivity, which we refer to as tulips in keeping with the flower metaphor. Preliminary cut-off scores for all three groups are provided. In order to characterise the different sensitivity groups, we investigated group differences regarding the Big Five personality traits, as well as experimentally assessed emotional reactivity in an additional independent sample. According to these follow-up analyses, the three groups differed in neuroticism, extraversion and emotional reactivity to positive mood induction with orchids scoring significantly higher in neuroticism and emotional reactivity and lower in extraversion than the other two groups (dandelions also differed significantly from tulips). Findings suggest that environmental sensitivity is a continuous and normally distributed trait but that people fall into three distinct sensitive groups along a sensitivity continuum.

Sensitivity to Factors Underlying the Hiatus

NASA Technical Reports Server (NTRS)

Marvel, Kate; Schmidt, Gavin A.; Tsigaridis, Kostas; Cook, Benjamin I.

2015-01-01

Recent trends in global mean surface air temperature fall outside the 90 range predicted by models using the CMIP5 forcings and scenarios; this recent period of muted warming is dubbed the hiatus. The hiatus has attracted broad attention in both the popular press and the scientific literature, primarily because of its perceived implications for understanding long-term trends. Many hypotheses have been offered to explain the warming slowdown during the hiatus, and comprehensive studies of this period across multiple variables and spatial scales will likely improve our understanding of the physical mechanisms driving global temperature change and variability.We argue, however, that decadal temperature trends by themselves are unlikely to constrain future trajectories of global mean temperature and that the hiatus does not significantly revise our understanding of overall climate sensitivity. Instead, we demonstrate that, because of the poorly constrained nature of the hiatus, model-observation disagreements over this period may be resolvable via uncertainties in the observations, modeled internal variability, forcing estimates, or (more likely) some combination of all three factors. We define the hiatus interval as 1998-2012, endpoints judiciously chosen to minimize observed warming by including the large 1998 El Nio event and excluding 2014, an exceptionally warm year. Such choices are fundamentally subjective and cannot be considered random, so any probabilistic statements regarding the likelihood of this occurring need to be made carefully. Using this definition, the observed global temperature trend estimates from four datasets fall outside the 5-95 interval predicted by the CMIP5 models. Here we explore some of the plausible explanations for this discrepancy, and show that no unique explanation is likely to fully account for the hiatus.

Anxiety sensitivity in smokers with indicators of cardiovascular disease.

PubMed

Farris, Samantha G; Abrantes, Ana M

2017-09-01

There is growing recognition of the importance of understanding the nature of the associations between anxiety and cardiovascular disease (CVD), although limited research has examined mechanisms that may explain the anxiety-CVD link. Anxiety sensitivity (fear of anxiety-relevant somatic sensations) is a cognitive-affective risk factor implicated in the development of anxiety psychopathology and various behavioral risk factors for CVD, although has not been examined among individuals with CVD. Adult daily smokers (n = 619; 50.9% female; M age  = 44.0, SD = 13.67) completed an online survey that included the Anxiety Sensitivity Index-3 (ASI-3) and the Patient Health Questionnaire (PHQ). The presence of CVD was assessed via the presence of ≥1 of the following: heart attack, heart murmur, positive stress test, heart valve abnormality, angina, and heart failure. Smokers with CVD indicators (n = 66, 10.7%) had significantly higher scores on the ASI-3 (M = 33.5, SD = 22.15), relative to smokers without CVD (M = 22.0, SD = 17.92; Cohen's d = .57). Those with CVD were significantly more likely to have moderate or high anxiety sensitivity (66.7%) relative to those without CVD (49.4%). Physical and social concerns about the meaning of somatic sensations were common among smokers with CVD.

Sensitivity of Runway Occupancy Time (ROT) to Various Rollout and Turnoff (ROTO) Factors. Volume 1

NASA Technical Reports Server (NTRS)

Goldthorpe, S. H.

1997-01-01

The Terminal Area Productivity (TAP) research program was initiated by NASA to increase the airport capacity for transport aircraft operations. One element of the research program is called Low Visibility Landing and Surface Operations (LVLASO). A goal of the LVLASO research is to develop transport aircraft technologies which reduce Runway Occupancy Time (ROT) so that it does not become the limiting factor in the terminal area operations that determine the capacity of a runway. Under LVLASO, the objective of this study was to determine the sensitivity of ROT to various factors associated with the Rollout and Turnoff (ROTO) operation for transport aircraft. The following operational factors were studied and are listed in the order of decreasing ROT sensitivity: ice/flood runway surface condition, exit entrance ground speed, number of exits, high-speed exit locations and spacing, aircraft type, touchdown ground speed standard deviation, reverse thrust and braking method, accurate exit prediction capability, maximum reverse thrust availability, spiral-arc vs. circle-arc exit geometry, dry/slush/wet/snow runway surface condition, maximum allowed deceleration, auto asymmetric braking on exit, do not stow reverse thrust before the exit, touchdown longitudinal location standard deviation, flap setting, anti-skid efficiency, crosswind conditions, stopping on the exit and touchdown lateral offset.

The Nature of the Dietary Protein Impacts the Tissue-to-Diet 15N Discrimination Factors in Laboratory Rats

PubMed Central

Poupin, Nathalie; Bos, Cécile; Mariotti, François; Huneau, Jean-François; Tomé, Daniel; Fouillet, Hélène

2011-01-01

Due to the existence of isotope effects on some metabolic pathways of amino acid and protein metabolism, animal tissues are 15N-enriched relative to their dietary nitrogen sources and this 15N enrichment varies among different tissues and metabolic pools. The magnitude of the tissue-to-diet discrimination (Δ15N) has also been shown to depend on dietary factors. Since dietary protein sources affect amino acid and protein metabolism, we hypothesized that they would impact this discrimination factor, with selective effects at the tissue level. To test this hypothesis, we investigated in rats the influence of a milk or soy protein-based diet on Δ15N in various nitrogen fractions (urea, protein and non-protein fractions) of blood and tissues, focusing on visceral tissues. Regardless of the diet, the different protein fractions of blood and tissues were generally 15N-enriched relative to their non-protein fraction and to the diet (Δ15N>0), with large variations in the Δ15N between tissue proteins. Δ15N values were markedly lower in tissue proteins of rats fed milk proteins compared to those fed soy proteins, in all sampled tissues except in the intestine, and the amplitude of Δ15N differences between diets differed between tissues. Both between-tissue and between-diet Δ15N differences are probably related to modulations of the relative orientation of dietary and endogenous amino acids in the different metabolic pathways. More specifically, the smaller Δ15N values observed in tissue proteins with milk than soy dietary protein may be due to a slightly more direct channeling of dietary amino acids for tissue protein renewal and to a lower recycling of amino acids through fractionating pathways. In conclusion, the present data indicate that natural Δ15N of tissue are sensitive markers of the specific subtle regional modifications of the protein and amino acid metabolism induced by the protein dietary source. PMID:22132207

Granulocyte-colony–stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis

PubMed Central

Basso, Lilian; Lapointe, Tamia K.; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D.; Kurrasch, Deborah M.; Altier, Christophe

2017-01-01

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony–stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF–induced visceral pain in vivo. Finally, administration of G-CSF–neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron–microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain. PMID:28973941

Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

PubMed

Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

2017-10-17

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

Deficient cortical face-sensitive N170 responses and basic visual processing in schizophrenia.

PubMed

Maher, S; Mashhoon, Y; Ekstrom, T; Lukas, S; Chen, Y

2016-01-01

Face detection, an ability to identify a visual stimulus as a face, is impaired in patients with schizophrenia. It is unclear whether impaired face processing in this psychiatric disorder results from face-specific domains or stems from more basic visual domains. In this study, we examined cortical face-sensitive N170 response in schizophrenia, taking into account deficient basic visual contrast processing. We equalized visual contrast signals among patients (n=20) and controls (n=20) and between face and tree images, based on their individual perceptual capacities (determined using psychophysical methods). We measured N170, a putative temporal marker of face processing, during face detection and tree detection. In controls, N170 amplitudes were significantly greater for faces than trees across all three visual contrast levels tested (perceptual threshold, two times perceptual threshold and 100%). In patients, however, N170 amplitudes did not differ between faces and trees, indicating diminished face selectivity (indexed by the differential responses to face vs. tree). These results indicate a lack of face-selectivity in temporal responses of brain machinery putatively responsible for face processing in schizophrenia. This neuroimaging finding suggests that face-specific processing is compromised in this psychiatric disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

High indium non-polar InGaN clusters with infrared sensitivity grown by PAMBE

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

Mukundan, Shruti; Mohan, Lokesh; Chandan, Greeshma

2015-03-15

Studies on the optical properties of InGaN alloy of relatively higher indium content are of potential interest to understand the effect of indium content on the optical band gap of epitaxial InGaN. We report the growth of self assembled non-polar high indium clusters of In{sub 0.55}Ga{sub 0.45}N over non-polar (11-20) a-plane In{sub 0.17}Ga{sub 0.83}N epilayer grown on a-plane (11-20)GaN/(1-102) r-plane sapphire substrate using plasma assisted molecular beam epitaxy (PAMBE). Such structures are potential candidates for high brightness LEDs emitting in longer wavelengths. The high resolution X-ray diffraction studies revealed the formation of two distinct compositions of In{sub x}Ga{sub 1−x}N alloys,more » which were further confirmed by photoluminescence studies. A possible mechanism for the formation of such structure was postulated which was supported with the results obtained by energy dispersive X-ray analysis. The structure hence grown when investigated for photo-detecting properties, showed sensitivity to both infrared and ultraviolet radiations due to the different composition of InGaN region.« less

Hearing impairment, cognition and speech understanding: exploratory factor analyses of a comprehensive test battery for a group of hearing aid users, the n200 study

PubMed Central

Rönnberg, Jerker; Lunner, Thomas; Ng, Elaine Hoi Ning; Lidestam, Björn; Zekveld, Adriana Agatha; Sörqvist, Patrik; Lyxell, Björn; Träff, Ulf; Yumba, Wycliffe; Classon, Elisabet; Hällgren, Mathias; Larsby, Birgitta; Signoret, Carine; Pichora-Fuller, M. Kathleen; Rudner, Mary; Danielsson, Henrik; Stenfelt, Stefan

2016-01-01

Abstract Objective: The aims of the current n200 study were to assess the structural relations between three classes of test variables (i.e. HEARING, COGNITION and aided speech-in-noise OUTCOMES) and to describe the theoretical implications of these relations for the Ease of Language Understanding (ELU) model. Study sample: Participants were 200 hard-of-hearing hearing-aid users, with a mean age of 60.8 years. Forty-three percent were females and the mean hearing threshold in the better ear was 37.4 dB HL. Design: LEVEL1 factor analyses extracted one factor per test and/or cognitive function based on a priori conceptualizations. The more abstract LEVEL 2 factor analyses were performed separately for the three classes of test variables. Results: The HEARING test variables resulted in two LEVEL 2 factors, which we labelled SENSITIVITY and TEMPORAL FINE STRUCTURE; the COGNITIVE variables in one COGNITION factor only, and OUTCOMES in two factors, NO CONTEXT and CONTEXT. COGNITION predicted the NO CONTEXT factor to a stronger extent than the CONTEXT outcome factor. TEMPORAL FINE STRUCTURE and SENSITIVITY were associated with COGNITION and all three contributed significantly and independently to especially the NO CONTEXT outcome scores (R2 = 0.40). Conclusions: All LEVEL 2 factors are important theoretically as well as for clinical assessment. PMID:27589015

Negative urgency and reward/punishment sensitivity in intermittent explosive disorder.

PubMed

Puhalla, Alexander A; Ammerman, Brooke A; Uyeji, Lauren L; Berman, Mitchell E; McCloskey, Michael S

2016-09-01

Intermittent explosive disorder (IED) is the sole psychiatric diagnosis in which affective aggression is the cardinal symptom. Previous research has been equivocal with regard to the relationship between IED and impulsivity. This inconsistency may reflect the varied facets of impulsivity, with some aspects of impulsivity (e.g. negative urgency) as well as some overlapping, albeit distinct constructs (e.g. reward and punishment sensitivity) yet to be studied. The present study compared individuals diagnosed with IED (n=81) with psychiatric controls (PCs; n=52) and healthy volunteers (HVs; n=58) on the impulsivity domains of negative and positive urgency, perseverance, sensation seeking, and premeditation, as well as on reward and punishment sensitivity. We hypothesized that individuals with IED would show greater negative and positive urgency, reward sensitivity, punishment sensitivity, with negative urgency independently predicting IED status. We also hypothesized that negative urgency would predict levels of anger, aggression, and aggression control among those with IED. The IED participants reported greater negative urgency than both comparison groups, and greater levels of positive urgency, reward sensitivity, and punishment sensitivity compared to HVs. Further, heightened negative urgency was the sole predictor an IED diagnosis. Within the IED group negative urgency uniquely predicted decreased aggression control and increased trait anger. Limitations included reliance on self-report measures to assess RS/PS, impulsivity, and aggression. These findings suggest that negative urgency is a key factor associated with IED and is associated with dampened control of aggression within those with IED. Copyright © 2016 Elsevier B.V. All rights reserved.

Dye molecular structure device open-circuit voltage correlation in Ru(II) sensitizers with heteroleptic tridentate chelates for dye-sensitized solar cells.

PubMed

Wu, Kuan-Lin; Li, Cheng-Hsuan; Chi, Yun; Clifford, John N; Cabau, Lydia; Palomares, Emilio; Cheng, Yi-Ming; Pan, Hsiao-An; Chou, Pi-Tai

2012-05-02

Dicarboxyterpyridine chelates with π-conjugated pendant groups attached at the 5- or 6-position of the terminal pyridyl unit were synthesized. Together with 2,6-bis(5-pyrazolyl)pyridine, these were used successfully to prepare a series of novel heteroleptic, bis-tridentate Ru(II) sensitizers, denoted as TF-11-14. These dyes show excellent performance in dye-sensitized solar cells (DSCs) under AM1.5G simulated sunlight at a light intensity of 100 mW cm(-2) in comparison with a reference device containing [Ru(Htctpy)(NCS)(3)][TBA](3) (N749), where H(3)tctpy and TBA are 4,4',4"-tricarboxy-2,2':6',2"-terpyridine and tetra-n-butylammonium cation, respectively. In particular, the sensitizer TF-12 gave a short-circuit photocurrent of 19.0 mA cm(-2), an open-circuit voltage (V(OC)) of 0.71 V, and a fill factor of 0.68, affording an overall conversion efficiency of 9.21%. The increased conjugation conferred to the TF dyes by the addition of the π-conjugated pendant groups increases both their light-harvesting and photovoltaic energy conversion capability in comparison with N749. Detailed recombination processes in these devices were probed by various spectroscopic and dynamics measurements, and a clear correlation between the device V(OC) and the cell electron lifetime was established. In agreement with several other recent studies, the results demonstrate that high efficiencies can also be achieved with Ru(II) sensitizers that do not contain thiocyanate ancillaries. This bis-tridentate, dual-carboxy anchor configuration thus serves as a prototype for future omnibearing design of highly efficient Ru(II) sensitizers suited for use in DSCs. © 2012 American Chemical Society

Two Disease-Causing SNAP-25B Mutations Selectively Impair SNARE C-terminal Assembly.

PubMed

Rebane, Aleksander A; Wang, Bigeng; Ma, Lu; Qu, Hong; Coleman, Jeff; Krishnakumar, Shyam; Rothman, James E; Zhang, Yongli

2018-02-16

Synaptic exocytosis relies on assembly of three soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins into a parallel four-helix bundle to drive membrane fusion. SNARE assembly occurs by stepwise zippering of the vesicle-associated SNARE (v-SNARE) onto a binary SNARE complex on the target plasma membrane (t-SNARE). Zippering begins with slow N-terminal association followed by rapid C-terminal zippering, which serves as a power stroke to drive membrane fusion. SNARE mutations have been associated with numerous diseases, especially neurological disorders. It remains unclear how these mutations affect SNARE zippering, partly due to difficulties to quantify the energetics and kinetics of SNARE assembly. Here, we used single-molecule optical tweezers to measure the assembly energy and kinetics of SNARE complexes containing single mutations I67T/N in neuronal SNARE synaptosomal-associated protein of 25kDa (SNAP-25B), which disrupt neurotransmitter release and have been implicated in neurological disorders. We found that both mutations significantly reduced the energy of C-terminal zippering by ~10 k B T, but did not affect N-terminal assembly. In addition, we observed that both mutations lead to unfolding of the C-terminal region in the t-SNARE complex. Our findings suggest that both SNAP-25B mutations impair synaptic exocytosis by destabilizing SNARE assembly, rather than stabilizing SNARE assembly as previously proposed. Therefore, our measurements provide insights into the molecular mechanism of the disease caused by SNARE mutations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitive and Structure-Informative N-Glycosylation Analysis by MALDI-MS; Ionization, Fragmentation, and Derivatization

PubMed Central

Nishikaze, Takashi

2017-01-01

Mass spectrometry (MS) has become an indispensable tool for analyzing post translational modifications of proteins, including N-glycosylated molecules. Because most glycosylation sites carry a multitude of glycans, referred to as “glycoforms,” the purpose of an N-glycosylation analysis is glycoform profiling and glycosylation site mapping. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has unique characteristics that are suited for the sensitive analysis of N-glycosylated products. However, the analysis is often hampered by the inherent physico-chemical properties of N-glycans. Glycans are highly hydrophilic in nature, and therefore tend to show low ion yields in both positive- and negative-ion modes. The labile nature and complicated branched structures involving various linkage isomers make structural characterization difficult. This review focuses on MALDI-MS-based approaches for enhancing analytical performance in N-glycosylation research. In particular, the following three topics are emphasized: (1) Labeling for enhancing the ion yields of glycans and glycopeptides, (2) Negative-ion fragmentation for less ambiguous elucidation of the branched structure of N-glycans, (3) Derivatization for the stabilization and linkage isomer discrimination of sialic acid residues. PMID:28794918

Personality traits as vulnerability factors in body dysmorphic disorder.

PubMed

Schieber, Katharina; Kollei, Ines; de Zwaan, Martina; Müller, Astrid; Martin, Alexandra

2013-11-30

Cognitive behavioural models consider certain personality traits to be risk factors for the development of Body Dysmorphic Disorder (BDD). Research on personality traits in BDD is scarce, therefore this study examined perfectionism, aesthetic sensitivity and the behavioural inhibition system (BIS) in BDD. Furthermore, the association between these personality traits and the extent of dysmorphic concerns was investigated. Individuals with BDD (n=58) and a population based control sample (n=2071), selected from a representative German population survey, completed self-report questionnaires assessing DSM-5 criteria of BDD, dysmorphic concerns, perfectionism, aesthetic sensitivity and BIS-reactivity. Individuals with BDD reported significantly higher degrees of perfectionism as well as of BIS-reactivity compared to the population based control sample, whereas the groups did not differ significantly regarding aesthetic sensitivity. However, for the total sample, each of the personality traits was related dimensionally to dysmorphic concerns. Current BDD models consider perfectionism and aesthetic sensitivity to be vulnerability factors. In addition to these concepts, the present study suggests that BIS-reactivity is related to BDD. Self-reported aesthetic sensitivity was not found to be specifically pronounced in BDD, but along with perfectionism and BIS-reactivity aesthetic sensitivity was generally associated with dysmorphic concerns. © 2013 Elsevier Ireland Ltd. All rights reserved.

An integrated approach to panic prevention targeting the empirically supported risk factors of smoking and anxiety sensitivity: theoretical basis and evidence from a pilot project evaluating feasibility and short-term efficacy.

PubMed

Feldner, Matthew T; Zvolensky, Michael J; Babson, Kimberly; Leen-Feldner, Ellen W; Schmidt, Norman B

2008-10-01

Consistent with a risk reduction model of targeted prevention, the present investigation piloted and empirically evaluated the feasibility and short-term efficacy of a first-generation panic prevention program that targeted two malleable risk factors for panic development-anxiety sensitivity and daily cigarette smoking. Members of a high risk cohort, defined by high levels of anxiety sensitivity and current daily smoking (n=96), were randomly assigned to either (1) a one session intervention focused on proximally increasing motivation to quit smoking and reducing anxiety sensitivity to distally prevent the development of panic or (2) a health information control condition of comparable length. Participants were followed for 6 months. Consistent with hypotheses, those in the treatment condition showed reduced anxiety sensitivity and this effect was maintained across the follow-up period. Limited evidence also suggested the intervention increased motivation to quit smoking. We discuss how this prevention protocol can be modified in the future to enhance its effects as part of second-generation larger-scale outcome evaluations.

Structure of Preschool Phonological Sensitivity: Overlapping Sensitivity to Rhyme, Words, Syllables, and Phonemes.

ERIC Educational Resources Information Center

Anthony, Jason L.; Lonigan, Christopher J.; Burgess, Stephen R.; Driscoll, Kimberly; Phillips, Beth M.; Cantor, Brenlee G.

2002-01-01

This study examined relations among sensitivity to words, syllables, rhymes, and phonemes in older and younger preschoolers. Confirmatory factor analyses found that a one-factor model best explained the date from both groups of children. Only variance common to all phonological sensitivity skills was related to print knowledge and rudimentary…

Studies on Early Allergic Sensitization in the Lithuanian Birth Cohort

PubMed Central

Dubakiene, Ruta; Rudzeviciene, Odilija; Butiene, Indre; Sezaite, Indre; Petronyte, Malvina; Vaicekauskaite, Dalia; Zvirbliene, Aurelija

2012-01-01

Cohort studies are of great importance in defining the mechanism responsible for the development of allergy-associated diseases, such as atopic dermatitis, allergic asthma, and allergic rhinoconjunctivitis. Although these disorders share genetic and environmental risk factors, it is still under debate whether they are linked or develop sequentially along an atopic pathway. The current study was aimed to determine the pattern of allergy sensitization in the Lithuanian birth cohort “Alergemol” (n = 1558) established as a part of the multicenter European birth cohort “EuroPrevall”. Early sensitization to food allergens in the “Alergemol” birth cohort was analysed. The analysis revealed 1.3% and 2.8% of symptomatic-sensitized subjects at 6 and 12 months of age, respectively. The sensitization pattern in response to different allergens in the group of infants with food allergy symptoms was studied using allergological methods in vivo and in vitro. The impact of maternal and environmental risk factors on the early development of food allergy in at 6 and 12 months of age was evaluated. Our data showed that maternal diet, diseases, the use of antibiotics, and tobacco smoke during pregnancy had no significant impact on the early sensitization to food allergens. However, infants of atopic mothers were significantly more often sensitized to egg as compared to the infants of nonatopic mothers. PMID:22606067

Is Ethical Sensitivity in Teaching Culturally Bound? Comparing Finnish and Iranian Teachers' Ethical Sensitivity

ERIC Educational Resources Information Center

Gholami, Khalil; Kuusisto, Elina; Tirri, Kirsi

2015-01-01

In this study, we investigated the culture-invariant and culture-dependent nature of teachers' ethical sensitivity in two countries. Our case study involves teachers from Finland (n = 864) representing Western culture, and from Iran (n = 556) representing Eastern culture. Culturally bound elements of ethical sensitivity were studied with the…

Applying n-bit floating point numbers and integers, and the n-bit filter of HDF5 to reduce file sizes of remote sensing products in memory-sensitive environments

NASA Astrophysics Data System (ADS)

Zinke, Stephan

2017-02-01

Memory sensitive applications for remote sensing data require memory-optimized data types in remote sensing products. Hierarchical Data Format version 5 (HDF5) offers user defined floating point numbers and integers and the n-bit filter to create data types optimized for memory consumption. The European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) applies a compaction scheme to the disseminated products of the Day and Night Band (DNB) data of Suomi National Polar-orbiting Partnership (S-NPP) satellite's instrument Visible Infrared Imager Radiometer Suite (VIIRS) through the EUMETSAT Advanced Retransmission Service, converting the original 32 bits floating point numbers to user defined floating point numbers in combination with the n-bit filter for the radiance dataset of the product. The radiance dataset requires a floating point representation due to the high dynamic range of the DNB. A compression factor of 1.96 is reached by using an automatically determined exponent size and an 8 bits trailing significand and thus reducing the bandwidth requirements for dissemination. It is shown how the parameters needed for user defined floating point numbers are derived or determined automatically based on the data present in a product.

Quantifying the importance of spatial resolution and other factors through global sensitivity analysis of a flood inundation model

NASA Astrophysics Data System (ADS)

Thomas Steven Savage, James; Pianosi, Francesca; Bates, Paul; Freer, Jim; Wagener, Thorsten

2016-11-01

Where high-resolution topographic data are available, modelers are faced with the decision of whether it is better to spend computational resource on resolving topography at finer resolutions or on running more simulations to account for various uncertain input factors (e.g., model parameters). In this paper we apply global sensitivity analysis to explore how influential the choice of spatial resolution is when compared to uncertainties in the Manning's friction coefficient parameters, the inflow hydrograph, and those stemming from the coarsening of topographic data used to produce Digital Elevation Models (DEMs). We apply the hydraulic model LISFLOOD-FP to produce several temporally and spatially variable model outputs that represent different aspects of flood inundation processes, including flood extent, water depth, and time of inundation. We find that the most influential input factor for flood extent predictions changes during the flood event, starting with the inflow hydrograph during the rising limb before switching to the channel friction parameter during peak flood inundation, and finally to the floodplain friction parameter during the drying phase of the flood event. Spatial resolution and uncertainty introduced by resampling topographic data to coarser resolutions are much more important for water depth predictions, which are also sensitive to different input factors spatially and temporally. Our findings indicate that the sensitivity of LISFLOOD-FP predictions is more complex than previously thought. Consequently, the input factors that modelers should prioritize will differ depending on the model output assessed, and the location and time of when and where this output is most relevant.

Affective and cognitive factors influencing sensitivity to probabilistic information.

PubMed

Tyszka, Tadeusz; Sawicki, Przemyslaw

2011-11-01

In study 1 different groups of female students were randomly assigned to one of four probabilistic information formats. Five different levels of probability of a genetic disease in an unborn child were presented to participants (within-subject factor). After the presentation of the probability level, participants were requested to indicate the acceptable level of pain they would tolerate to avoid the disease (in their unborn child), their subjective evaluation of the disease risk, and their subjective evaluation of being worried by this risk. The results of study 1 confirmed the hypothesis that an experience-based probability format decreases the subjective sense of worry about the disease, thus, presumably, weakening the tendency to overrate the probability of rare events. Study 2 showed that for the emotionally laden stimuli, the experience-based probability format resulted in higher sensitivity to probability variations than other formats of probabilistic information. These advantages of the experience-based probability format are interpreted in terms of two systems of information processing: the rational deliberative versus the affective experiential and the principle of stimulus-response compatibility. © 2011 Society for Risk Analysis.

RSV-hRV co-infection is a risk factor for recurrent bronchial obstruction and early sensitization 3 years after bronchiolitis.

PubMed

Amat, Flore; Plantard, Chloé; Mulliez, Aurélien; Petit, Isabelle; Rochette, Emmanuelle; Verdan, Matthieu; Henquell, Cécile; Labbé, Guillaume; Heraud, Marie Christine; Evrard, Bertrand; Labbé, André

2018-05-01

To assess risk factors of recurrent bronchial obstruction and allergic sensitization 3 years after an episode of acute bronchiolitis, whether after ambulatory care treatment or hospitalization. A monocentric prospective longitudinal study including infants aged under 1 year with acute bronchiolitis was performed, with clinical (severity score), biological (serum Krebs von den Lungen 6 antigen), and viral (14 virus by naso-pharyngeal suction detection) assessments. Follow-up included a quaterly telephone interview, and a final clinical examination at 3 years. Biological markers of atopy were also measured in peripheral blood, including specific IgEs towards aero- and food allergens. Complete data were available for 154 children. 46.8% of them had recurrent wheezing (RW). No difference was found according to initial severity, care at home or in the hospital, respiratory virus involved, or existence of co-infection. A familial history of atopy was identified as a risk factor for recurrent bronchial obstruction (60% for RW infants versus 39%, P = 0.02), as living in an apartment (35% versus 15%, P = 0.002). 18.6% of the infants were sensitized, with 48.1% of them sensitized to aeroallergens and 81.5% to food allergens. Multivariate analysis confirmed that a familial history of atopy (P = 0.02) and initial co-infection RSV-hRV (P = 0.02) were correlated with the risk of sensitization to aeroallergens at 3 years. Familial history of atopy and RSV-hRV co-infection are risk factors for recurrent bronchial obstruction and sensitization. © 2018 Wiley Periodicals, Inc.

Physiological Roles of Plant Post-Golgi Transport Pathways in Membrane Trafficking.

PubMed

Uemura, Tomohiro

2016-10-01

Membrane trafficking is the fundamental system through which proteins are sorted to their correct destinations in eukaryotic cells. Key regulators of this system include RAB GTPases and soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs). Interestingly, the numbers of RAB GTPases and SNAREs involved in post-Golgi transport pathways in plant cells are larger than those in animal and yeast cells, suggesting that plants have evolved unique and complex post-Golgi transport pathways. The trans-Golgi network (TGN) is an important organelle that acts as a sorting station in the post-Golgi transport pathways of plant cells. The TGN also functions as the early endosome, which is the first compartment to receive endocytosed proteins. Several endocytosed proteins on the plasma membrane (PM) are initially targeted to the TGN/EE, then recycled back to the PM or transported to the vacuole for degradation. The recycling and degradation of the PM localized proteins is essential for the development and environmental responses in plant. The present review describes the post-Golgi transport pathways that show unique physiological functions in plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating.

PubMed

Rogers, Jason V; Arlow, Tim; Inkellis, Elizabeth R; Koo, Timothy S; Rose, Mark D

2013-12-01

During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide-sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway.

A regulon conserved in monocot and dicot plants defines a functional module in antifungal plant immunity

PubMed Central

Humphry, Matt; Bednarek, Paweł; Kemmerling, Birgit; Koh, Serry; Stein, Mónica; Göbel, Ulrike; Stüber, Kurt; Piślewska-Bednarek, Mariola; Loraine, Ann; Schulze-Lefert, Paul; Somerville, Shauna; Panstruga, Ralph

2010-01-01

At least two components that modulate plant resistance against the fungal powdery mildew disease are ancient and have been conserved since the time of the monocot–dicot split (≈200 Mya). These components are the seven transmembrane domain containing MLO/MLO2 protein and the syntaxin ROR2/PEN1, which act antagonistically and have been identified in the monocot barley (Hordeum vulgare) and the dicot Arabidopsis thaliana, respectively. Additionally, syntaxin-interacting N-ethylmaleimide sensitive factor adaptor protein receptor proteins (VAMP721/722 and SNAP33/34) as well as a myrosinase (PEN2) and an ABC transporter (PEN3) contribute to antifungal resistance in both barley and/or Arabidopsis. Here, we show that these genetically defined defense components share a similar set of coexpressed genes in the two plant species, comprising a statistically significant overrepresentation of gene products involved in regulation of transcription, posttranslational modification, and signaling. Most of the coexpressed Arabidopsis genes possess a common cis-regulatory element that may dictate their coordinated expression. We exploited gene coexpression to uncover numerous components in Arabidopsis involved in antifungal defense. Together, our data provide evidence for an evolutionarily conserved regulon composed of core components and clade/species-specific innovations that functions as a module in plant innate immunity. PMID:21098265

Preparation of the cortical reaction: maturation-dependent migration of SNARE proteins, clathrin, and complexin to the porcine oocyte's surface blocks membrane traffic until fertilization.

PubMed

Tsai, Pei-Shiue; van Haeften, Theo; Gadella, Bart M

2011-02-01

The cortical reaction is a calcium-dependent exocytotic process in which the content of secretory granules is released into the perivitellin space immediately after fertilization, which serves to prevent polyspermic fertilization. In this study, we investigated the involvement and the organization of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins in the docking and fusion of the cortical granule membrane with the oolemma in porcine oocytes. During meiotic maturation, secretory vesicles that were labeled with a granule-specific binding lectin, peanut agglutinin (PNA), migrated toward the oocyte's surface. This surface-orientated redistribution behavior was also observed for the oocyte-specific SNARE proteins SNAP23 and VAMP1 that colocalized with the PNA-labeled structures in the cortex area just under the oolemma and with the exclusive localization area of complexin (a trans-SNARE complex-stabilizing protein). The coming together of these proteins serves to prevent the spontaneous secretion of the docked cortical granules and to prepare the oocyte's surface for the cortical reaction, which should probably be immediately compensated for by a clathrin-mediated endocytosis. In vitro fertilization resulted in the secretion of the cortical granule content and the concomitant release of complexin and clathrin into the oocyte's cytosol, and this is considered to stimulate the observed endocytosis of SNARE-containing membrane vesicles.

A role for SNAP-25 but not VAMPs in store-mediated Ca2+ entry in human platelets

PubMed Central

Redondo, Pedro C; Harper, Alan G S; Salido, Ginés M; Pariente, Jose A; Sage, Stewart O; Rosado, Juan A

2004-01-01

Store-mediated Ca2+ entry (SMCE) is a major mechanism for Ca2+ influx in non-excitable cells. Recently, a conformational coupling mechanism allowing coupling between transient receptor potential channels (TRPCs) and IP3 receptors has been proposed to activate SMCE. Here we have investigated the role of two soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs), which are involved in membrane trafficking and docking, in SMCE in human platelets. We found that the synaptosome-associated protein (SNAP-25) and the vesicle-associated membrane proteins (VAMP) coimmunoprecipitate with hTRPC1 in platelets. Treatment with botulinum toxin (BoNT) E or with tetanus toxin (TeTx), induced cleavage and inactivation of SNAP-25 and VAMPs, respectively. BoNTs significantly reduced thapsigargin- (TG) and agonist-evoked SMCE. Treatment with BoNTs once SMCE had been activated decreased Ca2+ entry, indicating that SNAP-25 is required for the activation and maintenance of SMCE. In contrast, treatment with TeTx had no effect on either the activation or the maintenance of SMCE in platelets. Finally, treatment with BoNT E impaired the coupling between naturally expressed hTRPC1 and IP3 receptor type II in platelets. From these findings we suggest SNAP-25 has a role in SMCE in human platelets. PMID:15121806

A vesicle trafficking protein αSNAP regulates Paneth cell differentiation in vivo.

PubMed

Lechuga, Susana; Naydenov, Nayden G; Feygin, Alex; Jimenez, Antonio J; Ivanov, Andrei I

2017-05-13

A soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSNAP) is a multifunctional scaffolding protein that regulates intracellular vesicle trafficking and signaling. In cultured intestinal epithelial cells, αSNAP has been shown to be essential for cell survival, motility, and adhesion; however, its physiologic functions in the intestinal mucosa remain unknown. In the present study, we used a mouse with a spontaneous hydrocephalus with hop gait (hyh) mutation of αSNAP to examine the roles of this trafficking protein in regulating intestinal epithelial homeostasis in vivo. Homozygous hyh mice demonstrated decreased expression of αSNAP protein in the intestinal epithelium, but did not display gross abnormalities of epithelial architecture in the colon and ileum. Such αSNAP depletion attenuated differentiation of small intestinal epithelial enteroids ex vivo. Furthermore, αSNAP-deficient mutant animals displayed reduced formation of lysozyme granules in small intestinal crypts and decreased expression of lysozyme and defensins in the intestinal mucosa, which is indicative of defects in Paneth cell differentiation. By contrast, development of Goblet cells, enteroendocrine cells, and assembly of enterocyte apical junctions was not altered in hyh mutant mice. Our data revealed a novel role of αSNAP in the intestinal Paneth cell differentiation in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

A VESICLE TRAFFICKING PROTEIN αSNAP REGULATES PANETH CELL DIFFERENTIATION IN VIVO

PubMed Central

Lechuga, Susana; Naydenov, Nayden G.; Feygin, Alex; Jimenez, Antonio J.; Ivanov, Andrei I.

2017-01-01

A soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSNAP) is a multifunctional scaffolding protein that regulates intracellular vesicle trafficking and signaling. In cultured intestinal epithelial cells, αSNAP has been shown to be essential for cell survival, motility, and adhesion; however, its physiologic functions in the intestinal mucosa remain unknown. In the present study, we used a mouse with a spontaneous hydrocephalus with hop gait (hyh) mutation of αSNAP to examine the roles of this trafficking protein in regulating intestinal epithelial homeostasis in vivo. Homozygous hyh mice demonstrated decreased expression of αSNAP protein in the intestinal epithelium, but did not display gross abnormalities of epithelial architecture in the colon and ileum. Such αSNAP depletion attenuated differentiation of small intestinal epithelial enteroids ex vivo. Furthermore, αSNAP-deficient mutant animals displayed reduced formation of lysozyme granules in small intestinal crypts and decreased expression of lysozyme and defensins in the intestinal mucosa, which is indicative of defects in Paneth cell differentiation. By contrast, development of Goblet cells, enteroendocrine cells, and assembly of enterocyte apical junctions was not altered in hyh mutant mice. Our data revealed a novel role of αSNAP in the intestinal Paneth cell differentiation in vivo. PMID:28359759

Developmentally regulated switch in alternatively spliced SNAP-25 isoforms alters facilitation of synaptic transmission.

PubMed

Bark, Christina; Bellinger, Frederick P; Kaushal, Ashutosh; Mathews, James R; Partridge, L Donald; Wilson, Michael C

2004-10-06

Although the basic molecular components that promote regulated neurotransmitter release are well established, the contribution of these proteins as regulators of the plasticity of neurotransmission and refinement of synaptic connectivity during development is elaborated less fully. For example, during the period of synaptic growth and maturation in brain, the expression of synaptosomal protein 25 kDa (SNAP-25), a neuronal t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) essential for action potential-dependent neuroexocytosis, is altered through alternative splicing of pre-mRNA transcripts. We addressed the role of the two splice-variant isoforms of SNAP-25 with a targeted mouse mutation that impairs the shift from SNAP-25a to SNAP-25b. Most of these mutant mice die between 3 and 5 weeks of age, which coincides with the time when SNAP-25b expression normally reaches mature levels in brain and synapse formation is essentially completed. The altered expression of these SNAP-25 isoforms influences short-term synaptic function by affecting facilitation but not the initial probability of release. This suggests that mechanisms controlling alternative splicing between SNAP-25 isoforms contribute to a molecular switch important for survival that helps to guide the transition from immature to mature synaptic connections, as well as synapse regrowth and remodeling after neural injury.

SNARE interactions in membrane trafficking: a perspective from mammalian central synapses.

PubMed

Kavalali, Ege T

2002-10-01

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are a large family of proteins that are present on all organelles involved in intracellular vesicle trafficking and secretion. The interaction of complementary SNAREs found on opposing membranes presents an attractive lock-and-key mechanism, which may underlie the specificity of vesicle trafficking. Moreover, formation of the tight complex between a vesicle membrane SNARE and corresponding target membrane SNAREs could drive membrane fusion. In synapses, this tight complex, also referred to as the synaptic core complex, is essential for neurotransmitter release. However, recent observations in knockout mice lacking major synaptic SNAREs challenge the prevailing notion on the executive role of these proteins in fusion and open up several questions about their exact role(s) in neurotransmitter release. Persistence of a form of regulated neurotransmitter release in these mutant mice also raises the possibility that other cognate or non-cognate SNAREs may partially compensate for the loss of a particular SNARE. Future analysis of SNARE function in central synapses will also have implications for the role of these molecules in other vesicle trafficking events such as endocytosis and vesicle replenishment. Such analysis can provide a molecular basis for synaptic processes including certain forms of short-term synaptic plasticity. Copyright 2002 Wiley Periodicals, Inc.

ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition

PubMed Central

Wang, Belinda; Krall, Elsa Beyer; Aguirre, Andrew James; Kim, Miju; Widlund, Hans Ragnar; Doshi, Mihir Bhavik; Sicinska, Ewa; Sulahian, Rita; Goodale, Amy; Cowley, Glenn Spencer; Piccioni, Federica; Doench, John Gerard; Root, David Edward; Hahn, William Chun

2017-01-01

SUMMARY Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome scale CRISPR-Cas9 loss-of-function screens in two KRAS-mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, 4, and 5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages. ATXN1L deletion, which reduces CIC protein, or ectopic expression of ETV1, 4, or 5 also modulated sensitivity to trametinib. ATXN1L expression inversely correlates with response to MAPKi inhibition in clinical studies. These observations identify the ATXN1L-CIC-ETS transcription factor axis as a mediator of resistance to MAPKi. PMID:28178529

Study of the plant COPII vesicle coat subunits by functional complementation of yeast Saccharomyces cerevisiae mutants.

PubMed

De Craene, Johan-Owen; Courte, Fanny; Rinaldi, Bruno; Fitterer, Chantal; Herranz, Mari Carmen; Schmitt-Keichinger, Corinne; Ritzenthaler, Christophe; Friant, Sylvie

2014-01-01

The formation and budding of endoplasmic reticulum ER-derived vesicles depends on the COPII coat protein complex that was first identified in yeast Saccharomyces cerevisiae. The ER-associated Sec12 and the Sar1 GTPase initiate the COPII coat formation by recruiting the Sec23-Sec24 heterodimer following the subsequent recruitment of the Sec13-Sec31 heterotetramer. In yeast, there is usually one gene encoding each COPII protein and these proteins are essential for yeast viability, whereas the plant genome encodes multiple isoforms of all COPII subunits. Here, we used a systematic yeast complementation assay to assess the functionality of Arabidopsis thaliana COPII proteins. In this study, the different plant COPII subunits were expressed in their corresponding temperature-sensitive yeast mutant strain to complement their thermosensitivity and secretion phenotypes. Secretion was assessed using two different yeast cargos: the soluble α-factor pheromone and the membranous v-SNARE (vesicle-soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor) Snc1 involved in the fusion of the secretory vesicles with the plasma membrane. This complementation study allowed the identification of functional A. thaliana COPII proteins for the Sec12, Sar1, Sec24 and Sec13 subunits that could represent an active COPII complex in plant cells. Moreover, we found that AtSec12 and AtSec23 were co-immunoprecipitated with AtSar1 in total cell extract of 15 day-old seedlings of A. thaliana. This demonstrates that AtSar1, AtSec12 and AtSec23 can form a protein complex that might represent an active COPII complex in plant cells.

Correlates of Depressed Mothers' Sensitivity toward Their Infants: The Role of Maternal, Child, and Contextual Characteristics

ERIC Educational Resources Information Center

van Doesum, Karin T. M.; Hosman, Clemens M. H.; Riksen-Walraven, J. Marianne; Hoefnagels, Cees

2007-01-01

Objective: To examine various maternal, child, and contextual characteristics, as well as the number of risk factors present, to distinguish which factors explain variance in the sensitivity of depressed mothers toward their infants. Method: Participants were depressed mothers (n = 84) with their infants ages 1 month up to 1 year. Mothers were…

Eicosapentaenoic acid prevents TCDD-induced oxidative stress and inflammatory response by modulating MAP kinases and redox-sensitive transcription factors

PubMed Central

Palanisamy, Kalaiselvi; Krishnaswamy, Rajashree; Paramasivan, Poornima; Chih-Yang, Huang; Vishwanadha, Vijaya Padma

2015-01-01

Background and Purpose Oxidative stress and subsequent activation of inflammatory responses is a widely accepted consequence of exposure to environmental toxins. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a well-known environmental toxin, exerts its toxicity through many signalling mechanisms, with liver being the principal organ affected. However, an effective antidote to TCDD-induced toxicity is unknown. The present study evaluated the effect of eicosapentaenoic acid (EPA), an n3 fatty acid, on TCDD-induced toxicity. Experimental Approach In cultures of HepG2 cells, the EPA/AA ratio was determined using gas chromatography, oxidative stress and inflammatory responses through reactive oxygen species (ROS) levels, antioxidant status, [Ca2+]i, nuclear migration of two redox-sensitive transcription factors, NF-κB p65 and Nrf-2, expression of MAP kinase (p-Erk, p-p38), NF-κB p65, COX-2 and Nrf-2. Cellular changes in ΔΨm, acidic vesicular organelle formation, cell cycle analysis and scanning electron microscopy analysis were performed. Key Results EPA offered significant cytoprotection by increasing EPA/AA ratios in cell membranes, inhibiting ROS generation, enhancing antioxidant status and modulating nuclear translocation of redox-sensitive transcription factors (NF-κB p65 and Nrf-2) and expression of NF-κB p65, COX-2 and Nrf-2. Furthermore, TCDD-induced upstream events of MAPK phosphorylation, the increase in [Ca2+]i levels and cell surface changes in microvilli were significantly inhibited by EPA. EPA treatment maintained ΔΨm and prevented formation of acidic vesicular organelles. Conclusion and Implications The present study demonstrates for the first time some underlying molecular mechanisms of cytoprotection exerted by EPA against TCDD-induced oxidative stress and inflammatory responses. PMID:26177858

The skin sensitization potential of four alkylalkanolamines.

PubMed

Leung, H W; Blaszcak, D L

1998-04-01

The skin sensitization potential of 4 alkylalkanolamines (N-methylethanolamine, N,N-dimethylethanolamine, N-methyldiethanolamine and N,N-diethylethanolamine), was evaluated in a guinea pig maximation procedure by the method of Magnusson and Kligman. While all 4 alkylalkanolamines tested were irritating to the guinea pig skin, only N-methylethanolamine showed potential to induce allergic contact dermatitis. None of the remaining 3 alkylalkanolamines exhibited clear skin responses suggestive of sensitization.

N-Hydroxysuccinimide as an effective chemiluminescence coreactant for highly selective and sensitive detection.

PubMed

Saqib, Muhammad; Li, Suping; Gao, Wenyue; Majeed, Saadat; Qi, Liming; Liu, Zhongyuan; Xu, Guobao

2016-12-01

The development of novel coreactants for chemiluminescence is very important to improve performance and widen its applications without using any other catalyst. N-Hydroxysuccinimide (NHS), a highly popular amine-reactive, activating, or protecting reagent in biochemical applications and organic synthesis, has been explored as an efficient and stable chemiluminescence coreactant for the first time. The chemiluminescence intensity of the newly developed luminol-NHS system is about 22 times higher than that of the traditional luminol-H 2 O 2 system. Chemiluminescence of this system is dramatically enhanced by Co 2+ . This new chemiluminescence system is then applied for the highly selective and ultrasensitive detection of Co 2+ with limit of detection (0.01 nM) better than those of several conventional analytical methods. This system also enables the efficient detection of luminol (LOD = 7 pM) and NHS (LOD = 3.0 μM) with excellent sensitivity. This chemiluminescence method was then also utilized to detect Co 2+ in tap water and blue silica gel with excellent recoveries in the range 99.20-103.07 %. This novel chemiluminescence system has several advantages, including simple, cost-effective, highly sensitive, selective, and wide linear range. We expect that this chemiluminescence system will be a promising candidate for chemical and biological sensing. Graphical Abstract Comparison of CL peak intensities of classical luminol-H 2 O 2 CL system and newly developed luminol-NHS CL system.

Development of luminol-N-hydroxyphthalimide chemiluminescence system for highly selective and sensitive detection of superoxide dismutase, uric acid and Co2.

PubMed

Saqib, Muhammad; Qi, Liming; Hui, Pan; Nsabimana, Anaclet; Halawa, Mohamed Ibrahim; Zhang, Wei; Xu, Guobao

2018-01-15

N-hydroxyphthalimide (NHPI), a well known reagent in organic synthesis and biochemical applications, has been developed as a stable and efficient chemiluminescence coreactant for the first time. It reacts with luminol much faster than N-hydroxysuccinimide, eliminating the need of a prereaction coil used in N-hydroxysuccinimide system. Without using prereaction coil, the chemiluminescence peak intensities of luminol-NHPI system are about 102 and 26 times greater than that of luminol-N-hydroxysuccinimide system and classical luminol-hydrogen peroxide system, respectively. The luminol-NHPI system achieves the highly sensitive detection of luminol (LOD = 70pM) and NHPI (LOD = 910nM). Based on their excellent quenching efficiencies, superoxide dismutase and uric acid are sensitively detected with LODs of 3ng/mL and 10pM, respectively. Co 2+ is also detected a LOD of 30pM by its remarkable enhancing effect. Noteworthily, our method is at least 4 orders of magnitude more sensitive than previously reported uric acid detection methods, and can detect uric acid in human urine and Co 2+ in tap and lake water real samples with excellent recoveries in the range of 96.35-102.70%. This luminol-NHPI system can be an important candidate for biochemical, clinical and environmental analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Rejection sensitivity prospectively predicts increased rumination.

PubMed

Pearson, Katherine A; Watkins, Edward R; Mullan, Eugene G

2011-10-01

Converging research findings indicate that rumination is correlated with a specific maladaptive interpersonal style encapsulating submissive (overly-accommodating, non-assertive and self-sacrificing) behaviours, and an attachment orientation characterised by rejection sensitivity. This study examined the prospective longitudinal relationship between rumination, the submissive interpersonal style, and rejection sensitivity by comparing two alternative hypotheses: (a) the submissive interpersonal style and rejection sensitivity prospectively predict increased rumination; (b) rumination prospectively predicts the submissive interpersonal style and rejection sensitivity. Currently depressed (n = 22), previously depressed (n = 42) and never depressed (n = 28) individuals completed self-report measures assessing depressive rumination and key psychosocial measures of interpersonal style and behaviours, at baseline and again six months later. Baseline rejection sensitivity prospectively predicted increased rumination six months later, after statistically controlling for baseline rumination, gender and depression. Baseline rumination did not predict the submissive interpersonal style or rejection sensitivity. The results provide a first step towards delineating a potential casual relationship between rejection sensitivity and rumination, and suggest the potential value of clinical assessment and intervention for both rejection sensitivity and rumination in individuals who present with either difficulty. Copyright © 2011 Elsevier Ltd. All rights reserved.

Disgust sensitivity and eating disorder symptoms in a non-clinical population.

PubMed

Mayer, Birgit; Muris, Peter; Bos, Arjan E R; Suijkerbuijk, Chantal

2008-12-01

In order to further explore the relationship between disgust sensitivity and eating disorder symptoms, 2 studies were carried out. In the first study, 352 higher education students (166 women, 186 men) completed a set of questionnaires measuring various aspects of disgust sensitivity and eating disorder symptoms. A correlational analysis revealed that there were few significant correlations between disgust scales and eating pathology scores. One exception was the relation between disgust sensitivity and external eating behavior, although this link only emerged in women. To investigate this relationship in more detail, Study 2 confronted women high (n=29) and low (n=30) on external eating behavior with a series of disgusting and neutral pictures. It was hypothesized that women who scored high on external eating would display shorter viewing times of disgusting pictures (i.e., show more avoidance behavior) than women scoring low on external eating. However, this hypothesis was not confirmed by the data. Altogether, the results of these studies suggest that there seems to be no convincing relationship between disgust sensitivity and eating disorder symptomatology, thereby casting doubts on the role of this individual difference factor in the development of eating pathology.

40 CFR Table N-1 to Subpart N of... - CO2 Emission Factors for Carbonate-Based Raw Materials

Code of Federal Regulations, 2011 CFR

2011-07-01

...-Based Raw Materials N Table N-1 to Subpart N of Part 98 Protection of Environment ENVIRONMENTAL... Raw Materials Carbonate-basedraw material—mineral CO2 emission factor a Limestone—CaCO3 0.440 Dolomite... in units of metric tons of CO2 emitted per metric ton of carbonate-based raw material charged to the...

Source Apportionment of PM2.5 Mass and Optical Attenuation Over an Ecologically Sensitive Zone in Central India by Positive Matrix Factorization

NASA Astrophysics Data System (ADS)

Nirmalkar, J.; Raman, R. S.

2016-12-01

Ambient PM2.5 samples (N=366) were collected over an ecologically sensitive zone (Van Vihar National Park) in Bhopal, Central India for two years (01 January, 2012 to 31 December, 2013). Samples were collected using three co-located Mini-Vol® samplers on Teflon, Nylon, and Quartz filter substrates. The aerosol was then chemically characterized for water-soluble inorganic ions, elements, and carbon fractions (elemental carbon and organic carbon) using ion chromatography, ED-XRF, and thermal-optical EC/OC analyzer, respectively. The optical attenuation (at 370 nm and 800 nm) of PM2.5 aerosols was also determined by optical transmissometry (OT-21). The application of Positive matrix factorization (PMF) to a combination of PM2.5 mass, its ions, elements, carbon fractions, and optical attenuation and its outcomes will be discussed.

Molecular characterization of the staphylococcal multidrug resistance export protein QacC.

PubMed Central

Paulsen, I T; Brown, M H; Dunstan, S J; Skurray, R A

1995-01-01

The QacC polypeptide is a member of a family of small membrane proteins which confer resistance to toxic compounds. The staphylococcal qacC gene confers resistance to toxic organic cations via proton-dependent export. The membrane topology of the QacC polypeptide was investigated by constructing and analyzing a series of qacC-phoA and qacC-lacZ fusions. From these analyses, most of the predicted features of the QacC protein were verified, although data regarding the possible orientation of the COOH region were not conclusive. The role of the sole cysteine residue, Cys-42, in QacC was studied by using the sulfhydryl reagent N-ethylmaleimide and site-directed mutagenesis. N-Ethylmaleimide was shown to inhibit qacC-mediated ethidium export. Multiple amino acid substitutions were made for Cys-42, and mutations at this location had various effects on resistance specificity. This suggests that the Cys-42 residue may be located near a region of QacC that is involved in substrate recognition. Mutagenesis of conserved residues in QacC indicated that Tyr-59 and Trp-62 also play an essential structural or functional role in QacC. PMID:7751293

SNARE-mediated rapid lysosome fusion in membrane raft clustering and dysfunction of bovine coronary arterial endothelium

PubMed Central

Han, Wei-Qing; Xia, Min; Zhang, Chun; Zhang, Fan; Xu, Ming; Li, Ning-Jun

2011-01-01

The present study attempted to evaluate whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate lysosome fusion in response to death receptor activation and contribute to membrane raft (MR) clustering and consequent endothelial dysfunction in coronary arterial endothelial cells. By immunohistochemical analysis, vesicle-associated membrane proteins 2 (VAMP-2, vesicle-SNAREs) were found to be abundantly expressed in the endothelium of bovine coronary arteries. Direct lysosome fusion monitoring by N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl]pyridinium dibromide (FM1-43) quenching demonstrated that the inhibition of VAMP-2 with tetanus toxin or specific small interfering ribonucleic acid (siRNA) almost completely blocked lysosome fusion to plasma membrane induced by Fas ligand (FasL), a well-known MR clustering stimulator. The involvement of SNAREs was further confirmed by an increased interaction of VAMP-2 with a target-SNARE protein syntaxin-4 after FasL stimulation in coimmunoprecipitation analysis. Also, the inhibition of VAMP-2 with tetanus toxin or VAMP-2 siRNA abolished FasL-induced MR clustering, its colocalization with a NADPH oxidase unit gp91phox, and increased superoxide production. Finally, FasL-induced impairment of endothelium-dependent vasodilation was reversed by the treatment of bovine coronary arteries with tetanus toxin or VAMP-2 siRNA. VAMP-2 is critical to lysosome fusion in MR clustering, and this VAMP-2-mediated lysosome-MR signalosomes contribute to redox regulation of coronary endothelial function. PMID:21926345

The Arabidopsis R-SNARE VAMP721 Interacts with KAT1 and KC1 K+ Channels to Moderate K+ Current at the Plasma Membrane.

PubMed

Zhang, Ben; Karnik, Rucha; Wang, Yizhou; Wallmeroth, Niklas; Blatt, Michael R; Grefen, Christopher

2015-06-01

SNARE (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptor) proteins drive vesicle traffic, delivering membrane and cargo to target sites within the cell and at its surface. They contribute to cell homeostasis, morphogenesis, and pathogen defense. A subset of SNAREs, including the Arabidopsis thaliana SNARE SYP121, are known also to coordinate solute uptake via physical interactions with K(+) channels and to moderate their gating at the plasma membrane. Here, we identify a second subset of SNAREs that interact to control these K(+) channels, but with opposing actions on gating. We show that VAMPs (vesicle-associated membrane proteins), which target vesicles to the plasma membrane, also interact with and suppress the activities of the inward-rectifying K(+) channels KAT1 and KC1. Interactions were evident in yeast split-ubiquitin assays, they were recovered in vivo by ratiometric bimolecular fluorescence complementation, and they were sensitive to mutation of a single residue, Tyr-57, within the longin domain of VAMP721. Interaction was also recovered on exchange of the residue at this site in the homolog VAMP723, which normally localizes to the endoplasmic reticulum and otherwise did not interact. Functional analysis showed reduced channel activity and alterations in voltage sensitivity that are best explained by a physical interaction with the channel gates. These actions complement those of SYP121, a cognate SNARE partner of VAMP721, and lead us to propose that the channel interactions reflect a "hand-off" in channel control between the two SNARE proteins that is woven together with vesicle fusion. © 2015 American Society of Plant Biologists. All rights reserved.

Using Bayes factors for testing hypotheses about intervention effectiveness in addictions research

PubMed Central

Dienes, Zoltan; Muirhead, Colin; West, Robert

2016-01-01

Abstract Background and Aims It has been proposed that more use should be made of Bayes factors in hypothesis testing in addiction research. Bayes factors are the ratios of the likelihood of a specified hypothesis (e.g. an intervention effect within a given range) to another hypothesis (e.g. no effect). They are particularly important for differentiating lack of strong evidence for an effect and evidence for lack of an effect. This paper reviewed randomized trials reported in Addiction between January and June 2013 to assess how far Bayes factors might improve the interpretation of the data. Methods Seventy‐five effect sizes and their standard errors were extracted from 12 trials. Seventy‐three per cent (n = 55) of these were non‐significant (i.e. P > 0.05). For each non‐significant finding a Bayes factor was calculated using a population effect derived from previous research. In sensitivity analyses, a further two Bayes factors were calculated assuming clinically meaningful and plausible ranges around this population effect. Results Twenty per cent (n = 11) of the non‐significant Bayes factors were < ⅓ and 3.6% (n = 2) were > 3. The other 76.4% (n = 42) of Bayes factors were between ⅓ and 3. Of these, 26 were in the direction of there being an effect (Bayes factor > 1 and < 3); 12 tended to favour the hypothesis of no effect (Bayes factor < 1 and > ⅓); and for four there was no evidence either way (Bayes factor = 1). In sensitivity analyses, 13.3% of Bayes Factors were < ⅓ (n = 20), 62.7% (n = 94) were between ⅓ and 3 and 24.0% (n = 36) were > 3, showing good concordance with the main results. Conclusions Use of Bayes factors when analysing data from randomized trials of interventions in addiction research can provide important information that would lead to more precise conclusions than are obtained typically using currently prevailing methods. PMID:27347846

Interrelations of Justice, Rejection, Provocation, and Moral Disgust Sensitivity and Their Links with the Hostile Attribution Bias, Trait Anger, and Aggression

PubMed Central

Bondü, Rebecca; Richter, Philipp

2016-01-01

Several personality dispositions with common features capturing sensitivities to negative social cues have recently been introduced into psychological research. To date, however, little is known about their interrelations, their conjoint effects on behavior, or their interplay with other risk factors. We asked N = 349 adults from Germany to rate their justice, rejection, moral disgust, and provocation sensitivity, hostile attribution bias, trait anger, and forms and functions of aggression. The sensitivity measures were mostly positively correlated; particularly those with an egoistic focus, such as victim justice, rejection, and provocation sensitivity, hostile attributions and trait anger as well as those with an altruistic focus, such as observer justice, perpetrator justice, and moral disgust sensitivity. The sensitivity measures had independent and differential effects on forms and functions of aggression when considered simultaneously and when controlling for hostile attributions and anger. They could not be integrated into a single factor of interpersonal sensitivity or reduced to other well-known risk factors for aggression. The sensitivity measures, therefore, require consideration in predicting and preventing aggression. PMID:27303351

Greater absolute rates of N2O production and consumption with soil warming dwarf variations in denitrification enzyme temperature sensitivities across seasons

NASA Astrophysics Data System (ADS)

Tiemann, L. K.; Billings, S. A.

2010-12-01

denitrification (i.e. consumption of gross N2O production into N2) to a greater degree, and permit release of a relatively smaller proportion of the nitrate they consumed as N2O; b) the suite of enzymes responsible for N2O production and the one enzyme responsible for its consumption exhibit differential temperature sensitivities in their production and expression during winter months, but the sensitivity of these processes converges during warmer seasons; c) in spite of the smaller proportion of NO3- released as N2O with warming, warming’s positive influence on the amount of NO3- transformed by denitrifying organisms resulted in far greater absolute quantities of N2O released with incubation and seasonal warming. Continuing work explores the influence that temperature may exert on the relative abundances of denitrifying populations and their gene expression, and links these microbial characteristics to denitrification processes with warming. These data signify the importance of understanding enzyme kinetics in concert with microbial adaptation and acclimation as a factor governing the net fluxes of N2O from soil vs. its transformation into N2 with warming.

Examining the ethnoracial invariance of a bifactor model of anxiety sensitivity and the incremental validity of the physical domain-specific factor in a primary-care patient sample.

PubMed

Fergus, Thomas A; Kelley, Lance P; Griggs, Jackson O

2017-10-01

There is growing support for a bifactor conceptualization of the Anxiety Sensitivity Index-3 (ASI-3; Taylor et al., 2007), consisting of a General factor and 3 domain-specific factors (i.e., Physical, Cognitive, Social). Earlier studies supporting a bifactor model of the ASI-3 used samples that consisted of predominantly White respondents. In addition, extant research has yet to support the incremental validity of the Physical domain-specific factor while controlling for the General factor. The present study is an examination of a bifactor model of the ASI-3 and the measurement invariance of that model among an ethnoracially diverse sample of primary-care patients (N = 533). Results from multiple-group confirmatory factor analysis supported the configural and metric/scalar invariance of the bifactor model of the ASI-3 across self-identifying Black, Latino, and White respondents. The Physical domain-specific factor accounted for unique variance in an index of health anxiety beyond the General factor. These results provide support for the generalizability of a bifactor model of the ASI-3 across 3 ethnoracial groups, as well as indication of the incremental explanatory power of the Physical domain-specific factor. Study implications are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition.

PubMed

Wang, Belinda; Krall, Elsa Beyer; Aguirre, Andrew James; Kim, Miju; Widlund, Hans Ragnar; Doshi, Mihir Bhavik; Sicinska, Ewa; Sulahian, Rita; Goodale, Amy; Cowley, Glenn Spencer; Piccioni, Federica; Doench, John Gerard; Root, David Edward; Hahn, William Chun

2017-02-07

Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome-scale CRISPR-Cas9 loss-of-function screens in two KRAS mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, ETV4, and ETV5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages. ATXN1L deletion, which reduces CIC protein, or ectopic expression of ETV1, ETV4, or ETV5 also modulated sensitivity to trametinib. ATXN1L expression inversely correlates with response to MAPKi inhibition in clinical studies. These observations identify the ATXN1L-CIC-ETS transcription factor axis as a mediator of resistance to MAPKi. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors

PubMed Central

Farroni, Jeffrey S; McCool, Brian A

2004-01-01

the systems examine here, these effects are independent of both absolute expression level and any system-related alterations in the agonist binding site. We conclude that complex interactions between receptor composition and extrinsic factors may play a significant role in determining strychnine-sensitive glycine receptor partial agonist pharmacology. PMID:15301692

Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors.

PubMed

Farroni, Jeffrey S; McCool, Brian A

2004-08-09

, these effects are independent of both absolute expression level and any system-related alterations in the agonist binding site. We conclude that complex interactions between receptor composition and extrinsic factors may play a significant role in determining strychnine-sensitive glycine receptor partial agonist pharmacology.

Sequential N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin Measurements During Albumin Replacement in Patients With Severe Sepsis or Septic Shock.

PubMed

Masson, Serge; Caironi, Pietro; Fanizza, Caterina; Carrer, Sara; Caricato, Anselmo; Fassini, Paola; Vago, Tarcisio; Romero, Marilena; Tognoni, Gianni; Gattinoni, Luciano; Latini, Roberto

2016-04-01

Myocardial dysfunction is a frequent complication in patients with severe sepsis and can worsen the prognosis. We investigated whether circulating biomarkers related to myocardial function and injury predicted outcome and were associated with albumin replacement. A multicenter, randomized clinical trial about albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). Forty ICUs in Italy. Nine hundred and ninety-five patients with severe sepsis or septic shock. Randomization to albumin and crystalloid solutions or crystalloid solutions alone. Plasma concentrations of N- terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T were measured 1, 2, and 7 days after enrollment. We tested the relationship of single marker measurements or changes over time with clinical events, organ dysfunctions, albumin replacement, and ICU or 90-day mortality in the overall population and after stratification by shock. N-terminal pro-B-type natriuretic peptide levels were abnormal in 97.4% of the patients and high-sensitivity cardiac troponin T in 84.5%, with higher concentrations in those with shock. After extensive adjustments, N-terminal pro-B-type natriuretic peptide concentrations predicted ICU or 90-day mortality, better than high-sensitivity cardiac troponin T. Early changes in N-terminal pro-B-type natriuretic peptide or high-sensitivity cardiac troponin T concentrations were independently associated with subsequent mortality in patients with shock. Patients given albumin had significantly higher N-terminal pro-B-type natriuretic peptide levels; in addition, early rise in N-terminal pro-B-type natriuretic peptide was associated with a better outcome in this subgroup. Circulating N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T are frequently elevated in severe sepsis or septic shock and have relevant prognostic value, which may be important in monitoring the clinical efficacy of

What Do We Mean By Sensitivity Analysis? The Need For A Comprehensive Characterization Of Sensitivity In Earth System Models

NASA Astrophysics Data System (ADS)

Razavi, S.; Gupta, H. V.

2014-12-01

Sensitivity analysis (SA) is an important paradigm in the context of Earth System model development and application, and provides a powerful tool that serves several essential functions in modelling practice, including 1) Uncertainty Apportionment - attribution of total uncertainty to different uncertainty sources, 2) Assessment of Similarity - diagnostic testing and evaluation of similarities between the functioning of the model and the real system, 3) Factor and Model Reduction - identification of non-influential factors and/or insensitive components of model structure, and 4) Factor Interdependence - investigation of the nature and strength of interactions between the factors, and the degree to which factors intensify, cancel, or compensate for the effects of each other. A variety of sensitivity analysis approaches have been proposed, each of which formally characterizes a different "intuitive" understanding of what is meant by the "sensitivity" of one or more model responses to its dependent factors (such as model parameters or forcings). These approaches are based on different philosophies and theoretical definitions of sensitivity, and range from simple local derivatives and one-factor-at-a-time procedures to rigorous variance-based (Sobol-type) approaches. In general, each approach focuses on, and identifies, different features and properties of the model response and may therefore lead to different (even conflicting) conclusions about the underlying sensitivity. This presentation revisits the theoretical basis for sensitivity analysis, and critically evaluates existing approaches so as to demonstrate their flaws and shortcomings. With this background, we discuss several important properties of response surfaces that are associated with the understanding and interpretation of sensitivity. Finally, a new approach towards global sensitivity assessment is developed that is consistent with important properties of Earth System model response surfaces.

Further studies on the new high sensitive CaSO4:Dy thermostimulated luminescence phosphor.

PubMed

Lakshmanan, A R; Tomita, A

2002-01-01

CaSO4:Dy phosphor prepared by a new recipe (denoted as N) is nearly 50% more sensitive than the presently used one (denoted as P). N consists of needle shaped crystals while P is mostly quadrilateral. In P most of the grains in as-grown condition are >75 microm in size while in N most of the grains are <75 microm. While the sensitivity of P increases with grain size, an exactly opposite trend is seen with N since higher sized grains (>105 microm) in N are agglomerates of particles and hence are opaque. The detection threshold of N (14.4 microGy) is nearly 4 times lower than that of P (54.2 microGy). The major glow peak(s) in both the phosphors occur in the 460-490 K (187-217 degrees C) region. But the low temperature peak near 390 K (117 degrees C) is very prominent in P while its presence is insignificant in N. The post-irradiation storage stability of N at approximately 30 degrees C was tested up to a period of 25 d and found to be better than that of P. The emission spectra of P and N are characteristic of Dy3+. In P, the 480 nm to 570 nm emission intensity ratio varies slightly with glow peak temperature, unlike that of N. The Dy concentration quenching effect in N is less serious than that in P. The intrinsic UV sensitivity of N is nearly a factor of 20 times lower than that of P.

Neurocognitive assessment of emotional context sensitivity.

PubMed

Myruski, Sarah; Bonanno, George A; Gulyayeva, Olga; Egan, Laura J; Dennis-Tiwary, Tracy A

2017-10-01

Sensitivity to emotional context is an emerging construct for characterizing adaptive or maladaptive emotion regulation, but few measurement approaches exist. The current study combined behavioral and neurocognitive measures to assess context sensitivity in relation to self-report measures of adaptive emotional flexibility and well-being. Sixty-six adults completed an emotional go/no-go task using happy, fearful, and neutral faces as go and no-go cues, while EEG was recorded to generate event-related potentials (ERPs) reflecting attentional selection and discrimination (N170) and cognitive control (N2). Context sensitivity was measured as the degree of emotional facilitation or disruption in the go/no-go task and magnitude of ERP response to emotion cues. Participants self-reported on emotional flexibility, anxiety, and depression. Overall participants evidenced emotional context sensitivity, such that when happy faces were go stimuli, accuracy improved (greater behavioral facilitation), whereas when fearful faces were no-go stimuli, errors increased (disrupted behavioral inhibition). These indices predicted emotional flexibility and well-being: Greater behavioral facilitation following happy cues was associated with lower depression and anxiety, whereas greater disruption in behavioral inhibition following fearful cues was associated with lower flexibility. ERP indices of context sensitivity revealed additional associations: Greater N2 to fear go cues was associated with less anxiety and depression, and greater N2 and N170 to happy and fear no-go cues, respectively, were associated with greater emotional flexibility and well-being. Results suggest that pleasant and unpleasant emotions selectively enhance and disrupt components of context sensitivity, and that behavioral and ERP indices of context sensitivity predict flexibility and well-being.

Downregulation of transcription factor GATA4 sensitizes human hepatoblastoma cells to doxorubicin-induced apoptosis.

PubMed

Soini, Tea; Pihlajoki, Marjut; Kyrönlahti, Antti; Andersson, Leif C; Wilson, David B; Heikinheimo, Markku

2017-03-01

Hepatoblastoma, the most common type of pediatric liver cancer, is treated with a combination of surgery and chemotherapy. An essential drug in the treatment of hepatoblastoma is doxorubicin, which in high doses is cardiotoxic. This adverse effect is due to downregulation of cardiac expression of transcription factor GATA4, leading in turn to diminished levels of anti-apoptotic BCL2 (B-cell lymphoma 2) protein family members. GATA4 is also expressed in early fetal liver, but absent from normal postnatal hepatocytes. However, GATA4 is highly expressed in hepatoblastoma tissue. In this study, we assessed the role of GATA4 in doxorubicin-induced apoptosis of hepatoblastoma cells. Herein, we demonstrate that doxorubicin decreases GATA4 expression and alters the expression pattern of BCL2 family members, most profoundly that of BCL2 and BAK, in the HUH6 hepatoblastoma cell line. Silencing of GATA4 by siRNA prior to doxorubicin treatment sensitizes HUH6 cells to the apoptotic effect of this drug by further shifting the balance of BCL2 family members to the pro-apoptotic direction. Specifically, expression levels of anti-apoptotic BCL2 were decreased and pro-apoptotic BID were increased after GATA4 silencing. On the whole, our results indicate that since high endogenous levels of transcription factor GATA4 likely protect hepatoblastoma cells from doxorubicin-induced apoptosis, these cells can be rendered more sensitive to the drug by downregulation of GATA4.

Indoor risk factors for cough and their relation to wheeze and sensitization in Chilean young adults.

PubMed

Potts, James F; Rona, Roberto J; Oyarzun, Manuel J; Amigo, Hugo; Bustos, Patricia

2008-04-01

We assessed the effects of indoor risk factors, including smoking, on different types of cough and on cough and wheeze in combination. Our sample was composed of 1232 men and women residing in a semirural area of Chile. We used a standardized questionnaire, sensitization to 8 allergens, and bronchial hyperresponsiveness to methacholine to assess cough and wheeze characteristics. Information was gathered on dampness, mold, ventilation, heating, housing quality, smoking, and environmental tobacco smoke exposure. Most exposures were associated with cough alone or cough in combination with wheeze. Smoking, past smoking, and environmental tobacco smoke exposure were strongly associated with dry cough and wheeze. The use of coal for heating was associated with dry cough. Leaks, mold, and lack of kitchen ventilation were associated with cough and wheeze. Nocturnal cough and productive cough were associated with specific types of sensitization, but dry cough was not. Productive cough was associated with hyperresponsiveness to methacholine. Several different types of indoor exposures, including environmental tobacco smoke exposure, are important contributors to morbidity associated with cough and wheeze. A vigorous preventive strategy designed to lower exposures to indoor risk factors would lower rates of respiratory morbidity.

Indoor risk factors for cough and their relation to wheeze and sensitization in Chilean young adults

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

Potts, J.F.; Rona, R.J.; Oyarzun, M.J.

2008-04-15

We assessed the effects of indoor risk factors, including smoking, on different types of cough and on cough and wheeze in combination. Our sample was composed of 1232 men and women residing in a semi-rural area of Chile. We used a standardized questionnaire, sensitization to 8 allergens, and bronchial hyperresponsiveness to methacholine to assess cough and wheeze characteristics. Information was gathered on dampness, mold, ventilation, heating, housing quality, smoking, and environmental tobacco smoke exposure. Most exposures were associated with cough alone or cough in combination with wheeze. Smoking, past smoking, and environmental tobacco smoke exposure were strongly associated with drymore » cough and wheeze. The use of coal for heating was associated with dry cough. Leaks, mold, and lack of kitchen ventilation were associated with cough and wheeze. Nocturnal cough and productive cough were associated with specific types of sensitization, but dry cough was not. Productive cough was associated with hyperresponsiveness to methacholine. Several different types of indoor exposures, including environmental tobacco smoke exposure, are important contributors to morbidity associated with cough and wheeze. A vigorous preventive strategy designed to lower exposures to indoor risk factors would lower rates of respiratory morbidity.« less

Highly Sensitive and Automated Surface Enhanced Raman Scattering-based Immunoassay for H5N1 Detection with Digital Microfluidics.

PubMed

Wang, Yang; Ruan, Qingyu; Lei, Zhi-Chao; Lin, Shui-Chao; Zhu, Zhi; Zhou, Leiji; Yang, Chaoyong

2018-04-17

Digital microfluidics (DMF) is a powerful platform for a broad range of applications, especially immunoassays having multiple steps, due to the advantages of low reagent consumption and high automatization. Surface enhanced Raman scattering (SERS) has been proven as an attractive method for highly sensitive and multiplex detection, because of its remarkable signal amplification and excellent spatial resolution. Here we propose a SERS-based immunoassay with DMF for rapid, automated, and sensitive detection of disease biomarkers. SERS tags labeled with Raman reporter 4-mercaptobenzoic acid (4-MBA) were synthesized with a core@shell nanostructure and showed strong signals, good uniformity, and high stability. A sandwich immunoassay was designed, in which magnetic beads coated with antibodies were used as solid support to capture antigens from samples to form a beads-antibody-antigen immunocomplex. By labeling the immunocomplex with a detection antibody-functionalized SERS tag, antigen can be sensitively detected through the strong SERS signal. The automation capability of DMF can greatly simplify the assay procedure while reducing the risk of exposure to hazardous samples. Quantitative detection of avian influenza virus H5N1 in buffer and human serum was implemented to demonstrate the utility of the DMF-SERS method. The DMF-SERS method shows excellent sensitivity (LOD of 74 pg/mL) and selectivity for H5N1 detection with less assay time (<1 h) and lower reagent consumption (∼30 μL) compared to the standard ELISA method. Therefore, this DMF-SERS method holds great potentials for automated and sensitive detection of a variety of infectious diseases.

Nuclear Expression of GS28 Protein: A Novel Biomarker that Predicts Prognosis in Colorectal Cancers

PubMed Central

Lee, Sung Hak; Yoo, Hyung Jae; Rim, Do Eun; Cui, Yinji; Lee, Ahwon; Jung, Eun Sun; Oh, Seung Taek; Kim, Jun Gi; Kwon, Oh-Joo; Kim, Su Young; Jeong, Seong-Whan

2017-01-01

Aims: GS28 (Golgi SNARE protein, 28 kDa), a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) protein family, plays a critical role in mammalian endoplasmic reticulum (ER)-Golgi or intra-Golgi vesicle transport. To date, few researches on the GS28 protein in human cancer tissues have been reported. In this study, we assessed the prognostic value of GS28 in patients with colorectal cancer (CRC). Methods and results: We screened for GS28 expression using immunohistochemistry in 230 surgical CRC specimens. The CRCs were right-sided and left-sided in 28.3% (65/230) and 71.3% (164/230) of patients, respectively. GS28 staining results were available in 214 cases. Among these, there were 26 nuclear predominant cases and 188 non-nuclear predominant cases. Stromal GS28 expression was noted in 152 cases of CRC. GS28 nuclear predominant immunoreactivity was significantly associated with advanced tumour stage (p = 0.045) and marginally associated with perineural invasion (p = 0.064). Decreased GS28 expression in the stromal cells was significantly associated with lymph node metastasis (N stage; p = 0.036). GS28 expression was not associated with epidermal growth factor receptor (EGFR) immunohistochemical positivity or KRAS mutation status. Investigation of the prognostic value of GS28 with Kaplan-Meier analysis revealed a correlation with overall survival (p = 0.004). Cases with GS28 nuclear predominant expression had significantly poorer overall survival than those with a non-nuclear predominant pattern. Conclusions: Taken together, these results indicate that GS28 nuclear predominant expression could serve as a prognostic marker for CRC and may help in identifying aggressive forms of CRC. PMID:28638266

REDOX-SENSITIVE TRANSCRIPTION FACTORS EGR-1 AND SP1 IN THE PATHOGENESIS OF EXPERIMENTAL GASTRIC ULCER.

PubMed

Beregovyi, S M; Chervinska, T M; Dranitsina, A S; Szabo, S; Tolstanova, G M

2015-01-01

Changes in redox status of gastric mucosa cells are the main pathogenic factor of gastric erosion and gastric ulcer development. Pro-oxidants can affect cell transcription activity via changes in redox-sensitive transcription factors. Egr-1 and Sp-1 may regulate the transcription of genes that are associated with the pathogenesis of gastric ulcer (growthfactors, cell cycle regulators, etc.). The aim of the present study was to reveal the possible involvement of zinc-finger transcriptionfactors Egr-1 & Sp-1 in the molecular mechanisms underlying gastric lesions caused by aspirin administration and stress. Gastric ulcer was induced in male rats (180-220 g) by immobilization stress combined with water-immersion (IMO-WI) or aspirin gavage (10 mg/100 g). The rats were euthanized 20 min, 1 hour, or 3 hours following the ulcerogenic factor exposure. Protein expression was determined by Western blot analysis and RT-PCR; levels of SH-groups of proteins were determined by method of Ellman et al. Development of gastric ulcer lesions was associated with twofold (P < 0.05) decrease in concentration of protein SH-groups in the rat gastric mucosa. These changes were accompanied by significant (P < 0.05) increase in the expression of Egr-1 mRNA and protein in both gastric ulcer models, and the changes in IMO-WI were more profound. Increased levels of Egr-1 were associated with the decrease in SpI protein levels. We showed for the first time the competitive interaction between redox-sensitive transcription factors Egr-1 and Sp1 in the early phases of gastric ulcer development, which might facilitate inducible transcriptional activity of Egr-1 at the expense of reduction in Sp1 activity.

Understanding the role of injury/illness sensitivity and anxiety sensitivity in (automatic) pain processing: an examination using the extrinsic affective simon task.

PubMed

Vancleef, Linda M G; Peters, Madelon L; Gilissen, Susan M P; De Jong, Peter J

2007-07-01

Three fundamental fears are assumed to underlie psychopathology: Anxiety Sensitivity (AS), Injury/illness sensitivity (IS), and Fear of Negative Evaluation (FNE). Both AS and IS may form risk factors for the development and exacerbation of chronic pain. The current research examines the relation between these fears and automatic threat appraisal for pain-related stimuli. Study 1 (n=48) additionally examined content-specific associations of AS and FNE with the automatic threat appraisal of, respectively, panic and social evaluative cues. Study 2 (n=60) additionally focused on the association of IS and AS with the engagement in health protecting behavior, and the use of health care services. Both studies found evidence for an automatic threat appraisal of aversive stimuli. Study 2 demonstrated a positive association between the automatic threat appraisal for pain-related stimuli and individuals' IS levels. IS was found to be the single best predictor of the tendency to engage in health protecting behavior, whereas AS was the single best predictor of the reported use of health care services. This study contributes to the field of knowledge on putative risk factors for chronic pain. Results demonstrate an automatic threat appraisal toward pain-related stimuli that is related to vulnerability traits for pain. This automatic threat appraisal might initiate relatively spontaneous (nonstrategic) pain-maintaining behavioral responses.

Evaluation of Intercontinental Transport of Ozone Using Full-tagged, Tagged-N and Sensitivity Methods

NASA Astrophysics Data System (ADS)

Guo, Y.; Liu, J.; Mauzerall, D. L.; Emmons, L. K.; Horowitz, L. W.; Fan, S.; Li, X.; Tao, S.

2014-12-01

Long-range transport of ozone is of great concern, yet the source-receptor relationships derived previously depend strongly on the source attribution techniques used. Here we describe a new tagged ozone mechanism (full-tagged), the design of which seeks to take into account the combined effects of emissions of ozone precursors, CO, NOx and VOCs, from a particular source, while keeping the current state of chemical equilibrium unchanged. We label emissions from the target source (A) and background (B). When two species from A and B sources react with each other, half of the resulting products are labeled A, and half B. Thus the impact of a given source on downwind regions is recorded through tagged chemistry. We then incorporate this mechanism into the Model for Ozone and Related chemical Tracers (MOZART-4) to examine the impact of anthropogenic emissions within North America, Europe, East Asia and South Asia on ground-level ozone downwind of source regions during 1999-2000. We compare our results with two previously used methods -- the sensitivity and tagged-N approaches. The ozone attributed to a given source by the full-tagged method is more widely distributed spatially, but has weaker seasonal variability than that estimated by the other methods. On a seasonal basis, for most source/receptor pairs, the full-tagged method estimates the largest amount of tagged ozone, followed by the sensitivity and tagged-N methods. In terms of trans-Pacific influence of ozone pollution, the full-tagged method estimates the strongest impact of East Asian (EA) emissions on the western U.S. (WUS) in MAM and JJA (~3 ppbv), which is substantially different in magnitude and seasonality from tagged-N and sensitivity studies. This difference results from the full-tagged method accounting for the maintenance of peroxy radicals (e.g., CH3O2, CH3CO3, and HO2), in addition to NOy, as effective reservoirs of EA source impact across the Pacific, allowing for a significant contribution to

High quality factor manganese-doped aluminum lumped-element kinetic inductance detectors sensitive to frequencies below 100 GHz

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

Jones, G.; Johnson, B. R.; Abitbol, M. H.

Aluminum lumped-element kinetic inductance detectors (LEKIDs) sensitive to millimeter-wave photons have been shown to exhibit high quality factors, making them highly sensitive and multiplexable. The superconducting gap of aluminum limits aluminum LEKIDs to photon frequencies above 100 GHz. Manganese-doped aluminum (Al-Mn) has a tunable critical temperature and could therefore be an attractive material for LEKIDs sensitive to frequencies below 100 GHz if the internal quality factor remains sufficiently high when manganese is added to the film. To investigate, we measured some of the key properties of Al-Mn LEKIDs. A prototype eight-element LEKID array was fabricated using a 40 nm thickmore » film of Al-Mn deposited on a 500 μm thick high-resistivity, float-zone silicon substrate. The manganese content was 900 ppm, the measured T c = 694 ± 1mK, and the resonance frequencies were near 150 MHz. Using measurements of the forward scattering parameter S 21 at various bath temperatures between 65 and 250 mK, we determined that the Al-Mn LEKIDs we fabricated have internal quality factors greater than 2 × 10 5, which is high enough for millimeter-wave astrophysical observations. In the dark conditions under which these devices were measured, the fractional frequency noise spectrum shows a shallow slope that depends on bath temperature and probe tone amplitude, which could be two-level system noise. In conclusion, the anticipated white photon noise should dominate this level of low-frequency noise when the detectors are illuminated with millimeter-waves in future measurements. The LEKIDs responded to light pulses from a 1550 nm light-emitting diode, and we used these light pulses to determine that the quasiparticle lifetime is 60 μs.« less

High quality factor manganese-doped aluminum lumped-element kinetic inductance detectors sensitive to frequencies below 100 GHz

DOE PAGES

Jones, G.; Johnson, B. R.; Abitbol, M. H.; ...

2017-05-29

Aluminum lumped-element kinetic inductance detectors (LEKIDs) sensitive to millimeter-wave photons have been shown to exhibit high quality factors, making them highly sensitive and multiplexable. The superconducting gap of aluminum limits aluminum LEKIDs to photon frequencies above 100 GHz. Manganese-doped aluminum (Al-Mn) has a tunable critical temperature and could therefore be an attractive material for LEKIDs sensitive to frequencies below 100 GHz if the internal quality factor remains sufficiently high when manganese is added to the film. To investigate, we measured some of the key properties of Al-Mn LEKIDs. A prototype eight-element LEKID array was fabricated using a 40 nm thickmore » film of Al-Mn deposited on a 500 μm thick high-resistivity, float-zone silicon substrate. The manganese content was 900 ppm, the measured T c = 694 ± 1mK, and the resonance frequencies were near 150 MHz. Using measurements of the forward scattering parameter S 21 at various bath temperatures between 65 and 250 mK, we determined that the Al-Mn LEKIDs we fabricated have internal quality factors greater than 2 × 10 5, which is high enough for millimeter-wave astrophysical observations. In the dark conditions under which these devices were measured, the fractional frequency noise spectrum shows a shallow slope that depends on bath temperature and probe tone amplitude, which could be two-level system noise. In conclusion, the anticipated white photon noise should dominate this level of low-frequency noise when the detectors are illuminated with millimeter-waves in future measurements. The LEKIDs responded to light pulses from a 1550 nm light-emitting diode, and we used these light pulses to determine that the quasiparticle lifetime is 60 μs.« less

Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter

PubMed Central

1993-01-01

Tumor necrosis factor alpha (TNF-alpha), a cytokine with pleiotropic biological effects, is produced by a variety of cell types in response to induction by diverse stimuli. In this paper, TNF-alpha mRNA is shown to be highly induced in a murine T cell clone by stimulation with T cell receptor (TCR) ligands or by calcium ionophores alone. Induction is rapid, does not require de novo protein synthesis, and is completely blocked by the immunosuppressant cyclosporin A (CsA). We have identified a human TNF-alpha promoter element, kappa 3, which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene. In electrophoretic mobility shift assays, an oligonucleotide containing kappa 3 forms two DNA protein complexes with proteins that are present in extracts from unstimulated T cells. These complexes appear in nuclear extracts only after T cell stimulation. Induction of the inducible nuclear complexes is rapid, independent of protein synthesis, and blocked by CsA, and thus, exactly parallels the induction of TNF-alpha mRNA by TCR ligands or by calcium ionophore. Our studies indicate that the kappa 3 binding factor resembles the preexisting component of nuclear factor of activated T cells. Thus, the TNF-alpha gene is an immediate early gene in activated T cells and provides a new model system in which to study CsA-sensitive gene induction in activated T cells. PMID:8376940

Cultural differences in sensitivity to social context: detecting affective incongruity using the N400.

PubMed

Goto, Sharon G; Yee, Alicia; Lowenberg, Kelly; Lewis, Richard S

2013-01-01

East Asians and Asian-Americans tend to allocate relatively greater attention to background context compared to European Americans across a variety of cognitive and neural measures. We sought to extend these findings of cultural differences to affective stimuli using the N400, which has been shown to be sensitive to deep processing of affective information. The degree to which Asian-Americans and European Americans responded to semantic incongruity between emotionally expressive faces (i.e., smiling or frowning) and background affective scenes was measured. As predicted, Asian-Americans showed a greater N400 to incongruent trials than to congruent trials. In contrast, European Americans showed no difference in amplitude across the two conditions. Furthermore, greater affective N400 incongruity was associated with higher interdependent self-construals. These data suggest that Asian-Americans and those with interdependent self-construals process the relationship between perceived facial emotion and affective background context to a greater degree than European Americans and those with independent self-construals. Implications for neural and cognitive differences in everyday social interactions, and cultural differences in analytic and holistic thinking are discussed.

MARCKS Regulates Growth, Radiation Sensitivity and is a Novel Prognostic Factor for Glioma

PubMed Central

Jarboe, John S.; Anderson, Joshua C.; Duarte, Christine W.; Mehta, Tapan; Nowsheen, Somaira; Hicks, Patricia H.; Whitley, Alexander C.; Rohrbach, Timothy D.; McCubrey, Raymond O.; Chiu, Sherard; Burleson, Tamara M.; Bonner, James A.; Gillespie, G. Yancey; Yang, Eddy S.; Willey, Christopher D.

2013-01-01

Purpose This study assessed whether Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) can regulate glioblastoma (GBM) growth, radiation sensitivity and clinical outcome. Experimental Design MARCKS protein levels were analyzed in five GBM explant cell lines and eight patient-derived xenograft tumors by immunoblot, and these levels were correlated to proliferation rates and intracranial growth rates, respectively. Manipulation of MARCKS protein levels was assessed by lentiviral-mediated shRNA knockdown in the U251 cell line and MARCKS over-expression in the U87 cell line. The effect of manipulation of MARCKS on proliferation, radiation sensitivity and senescence was assessed. MARCKS gene expression was correlated with survival outcomes in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) Database and The Cancer Genome Atlas (TCGA). Results MARCKS protein expression was inversely correlated with GBM proliferation and intracranial xenograft growth rates. Genetic silencing of MARCKS promoted GBM proliferation and radiation resistance, while MARCKS overexpression greatly reduced GBM growth potential and induced senescence. We found MARCKS gene expression to be directly correlated with survival in both the REMBRANDT and TCGA databases. Specifically, patients with high MARCKS expressing tumors of the Proneural molecular subtype had significantly increased survival rates. This effect was most pronounced in tumors with unmethylated O6-methylguanine DNA methyltransferase (MGMT) promoters, a traditionally poor prognostic factor. Conclusions MARCKS levels impact GBM growth and radiation sensitivity. High MARCKS expressing GBM tumors are associated with improved survival, particularly with unmethylated MGMT promoters. These findings suggest the use of MARCKS as a novel target and biomarker for prognosis in the Proneural subtype of GBM. PMID:22619307

Nitrous oxide nitrification and denitrification 15N enrichment factors from Amazon forest soils.

PubMed

Pérez, Tibisay; Garcia-Montiel, Diana; Trumbore, Susan; Tyler, Stanley; de Camargo, Plínio; Moreira, Marcelo; Piccolo, Marisa; Cerri, Carlos

2006-12-01

The isotopic signatures of 15N and 18O in N2O emitted from tropical soils vary both spatially and temporally, leading to large uncertainty in the overall tropical source signature and thereby limiting the utility of isotopes in constraining the global N2O budget. Determining the reasons for spatial and temporal variations in isotope signatures requires that we know the isotope enrichment factors for nitrification and denitrification, the two processes that produce N2O in soils. We have devised a method for measuring these enrichment factors using soil incubation experiments and report results from this method for three rain forest soils collected in the Brazilian Amazon: soil with differing sand and clay content from the Tapajos National Forest (TNF) near Santarém, Pará, and Nova Vida Farm, Rondônia. The 15N enrichment factors for nitrification and denitrification differ with soil texture and site: -111 per thousand +/- 12 per thousand and -31 per thousand +/- 11 per thousand for a clay-rich Oxisol (TNF), -102 per thousand +/- 5 per thousand and -45 per thousand +/- 5 per thousand for a sandier Ultisol (TNF), and -10.4 per thousand +/- 3.5 per thousand (enrichment factor for denitrification) for another Ultisol (Nova Vida) soil, respectively. We also show that the isotopomer site preference (delta15Nalpha - delta15Nbeta, where alpha indicates the central nitrogen atom and beta the terminal nitrogen atom in N2O) may allow differentiation between processes of production and consumption of N2O and can potentially be used to determine the contributions of nitrification and denitrification. The site preferences for nitrification and denitrification from the TNF-Ultisol incubated soils are: 4.2 per thousand +/- 8.4 per thousand and 31.6 per thousand +/- 8.1 per thousand, respectively. Thus, nitrifying and denitrifying bacteria populations under the conditions of our study exhibit significantly different 15N site preference fingerprints. Our data set strongly suggests

Anxiety Sensitivity in Dermatological Patients.

PubMed

Dixon, Laura J; Lee, Aaron A; Viana, Andres G; McCowan, Nancye K; Brodell, Robert T; Tull, Matthew T

2016-01-01

Anxiety symptoms commonly occur in dermatological patients and can affect the severity of dermatological symptoms. Anxiety sensitivity (AS), defined as the fear of anxiety symptoms, is a well-supported cognitive vulnerability factor that may be particularly significant in these patients. This study compared the severity of AS between patients with psychodermatological (e.g., psoriasis) and nonpsychodermatological disorders (e.g., skin cancer). It was predicted that individuals with psychodermatological disorders would evidence significantly greater AS compared to individuals with nonpsychodermatological disorders. Adults presenting to outpatient dermatology clinics with psychodermatological (n = 63) and nonpsychodermatological (n = 52) conditions completed self-report questionnaires assessing sociodemographic characteristics, general anxiety, and AS. Individuals with psychodermatological conditions reported significantly greater AS compared to individuals with nonpsychodermatological conditions (p < 0.05). Social concerns of AS emerged as the only significant factor that differentiated these categories of dermatological diseases, odds ratio = 1.13, 95% CI: 1.02-1.24, after adjusting for general anxiety. These findings contribute to an advancing area of research linking AS and physical health problems. The results suggest that adjunctive cognitive-behavioral treatments targeting AS reductions could help patients with psychodermatological conditions. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

PubMed

Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

2017-01-01

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

Sensitivity to chromosomal breakage as risk factor in young adults with oral squamous cell carcinoma.

PubMed

Braakhuis, Boudewijn J M; Nieuwint, Aggie W M; Oostra, Anneke B; Joenje, Hans; Flach, Géke B; Graveland, A Peggy; Brakenhoff, Ruud H; Leemans, C René

2016-03-01

Oral squamous cell carcinoma (OSCC) may develop in young adults. In contrast to older patients, the well-known etiological factors, exposure to tobacco and alcohol, play a minor role in the carcinogenesis in this patient group. It has been suggested that an intrinsic susceptibility to environmental genotoxic exposures plays a role in the development of OSCC in these patients. The hypothesis was tested whether young OSCC patients have an increased sensitivity to induced chromosomal damage. Fourteen OSCC patients with an average age of 32 years (range 20-42) were selected. Peripheral blood lymphocytes and skin fibroblasts of patients and 14 healthy controls were subjected to the chromosome breakage test with Mitomycin C. This test is routinely used to identify Fanconi anemia patients, who are well-known for their inherited high sensitivity to this type of DNA damage, but also for the high risk to develop OSCC. Human papilloma virus status of the carcinomas was also determined. None of the 14 young patients with OSCC had an increased response in the MMC-chromosomal breakage test. All tumors tested negative for human papilloma virus. No evidence was obtained for the existence of a constitutional hypersensitivity to DNA chromosomal damage as a potential risk factor for OSCC in young adults. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effect of temperature and moisture on electrical resistance, strain sensitivity and crack sensitivity of steel fiber reinforced smart cement composite

NASA Astrophysics Data System (ADS)

Teomete, Egemen

2016-07-01

Earthquakes, material degradations and other environmental factors necessitate structural health monitoring (SHM). Metal foil strain gages used for SHM have low durability and low sensitivity. These factors motivated researchers to work on cement based strain sensors. In this study, the effects of temperature and moisture on electrical resistance, compressive and tensile strain gage factors (strain sensitivity) and crack sensitivity were determined for steel fiber reinforced cement based composite. A rapid increase of electrical resistance at 200 °C was observed due to damage occurring between cement paste, aggregates and steel fibers. The moisture—electrical resistance relationship was investigated. The specimens taken out of the cure were saturated with water and had a moisture content of 9.49%. The minimum electrical resistance was obtained at 9% moisture at which fiber-fiber and fiber-matrix contact was maximum and the water in micro voids was acting as an electrolyte, conducting electrons. The variation of compressive and tensile strain gage factors (strain sensitivities) and crack sensitivity were investigated by conducting compression, split tensile and notched bending tests with different moisture contents. The highest gage factor for the compression test was obtained at optimal moisture content, at which electrical resistance was minimum. The tensile strain gage factor for split tensile test and crack sensitivity increased by decreasing moisture content. The mechanisms between moisture content, electrical resistance, gage factors and crack sensitivity were elucidated. The relations of moisture content with electrical resistance, gage factors and crack sensitivities have been presented for the first time in this study for steel fiber reinforced cement based composites. The results are important for the development of self sensing cement based smart materials.

Botulinum and Tetanus Neurotoxin-Induced Blockade of Synaptic Transmission in Networked Cultures of Human and Rodent Neurons

PubMed Central

Beske, Phillip H.; Bradford, Aaron B.; Grynovicki, Justin O.; Glotfelty, Elliot J.; Hoffman, Katie M.; Hubbard, Kyle S.; Tuznik, Kaylie M.; McNutt, Patrick M.

2016-01-01

Clinical manifestations of tetanus and botulism result from an intricate series of interactions between clostridial neurotoxins (CNTs) and nerve terminal proteins that ultimately cause proteolytic cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and functional blockade of neurotransmitter release. Although detection of cleaved SNARE proteins is routinely used as a molecular readout of CNT intoxication in cultured cells, impaired synaptic function is the pathophysiological basis of clinical disease. Work in our laboratory has suggested that the blockade of synaptic neurotransmission in networked neuron cultures offers a phenotypic readout of CNT intoxication that more closely replicates the functional endpoint of clinical disease. Here, we explore the value of measuring spontaneous neurotransmission frequencies as novel and functionally relevant readouts of CNT intoxication. The generalizability of this approach was confirmed in primary neuron cultures as well as human and mouse stem cell-derived neurons exposed to botulinum neurotoxin serotypes A–G and tetanus neurotoxin. The sensitivity and specificity of synaptic activity as a reporter of intoxication was evaluated in assays representing the principal clinical and research purposes of in vivo studies. Our findings confirm that synaptic activity offers a novel and functionally relevant readout for the in vitro characterizations of CNTs. They further suggest that the analysis of synaptic activity in neuronal cell cultures can serve as a surrogate for neuromuscular paralysis in the mouse lethal assay, and therefore is expected to significantly reduce the need for terminal animal use in toxin studies and facilitate identification of candidate therapeutics in cell-based screening assays. PMID:26615023

Action of insecticidal N-alkylamides at site 2 of the voltage-sensitive sodium channel

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

Ottea, J.A.; Payne, G.T.; Soderlund, D.M.

1990-08-01

Nine synthetic N-alkylamides were examined as inhibitors of the specific binding of ({sup 3}H)batrachotoxinin A 20{alpha}-benzoate (({sup 3}H)BTX-B) to sodium channels and as activators of sodium uptake in mouse brain synaptoneurosomes. In the presence of scorpion (Leiurus quinquestriatus) venom, the six insecticidal analogues were active as both inhibitors of ({sup 3}H)BTX-B binding and stimulators of sodium uptake. These findings are consistent with an action of these compounds at the alkaloid activator recognition site (site 2) of the voltage-sensitive sodium channel. The three noninsecticidal N-alkylamides also inhibited ({sup 3}H)BTX-B binding but were ineffective as activators of sodium uptake. Concentration-response studies revealedmore » that some of the insecticidal amides also enhanced sodium uptake through a second, high-affinity interaction that does not involve site 2, but this secondary effect does not appear to be correlated with insecticidal activity. The activities of N-alkylamides as sodium channel activators were influenced by the length of the alkenyl chain and the location of unsaturation within the molecule. These results further define the actions of N-alkylamides on sodium channels and illustrate the significance of the multiple binding domains of the sodium channel as target sites for insect control agents.« less

Sensitivities Kernels of Seismic Traveltimes and Amplitudes for Quality Factor and Boundary Topography

NASA Astrophysics Data System (ADS)

Hsieh, M.; Zhao, L.; Ma, K.

2010-12-01

Finite-frequency approach enables seismic tomography to fully utilize the spatial and temporal distributions of the seismic wavefield to improve resolution. In achieving this goal, one of the most important tasks is to compute efficiently and accurately the (Fréchet) sensitivity kernels of finite-frequency seismic observables such as traveltime and amplitude to the perturbations of model parameters. In scattering-integral approach, the Fréchet kernels are expressed in terms of the strain Green tensors (SGTs), and a pre-established SGT database is necessary to achieve practical efficiency for a three-dimensional reference model in which the SGTs must be calculated numerically. Methods for computing Fréchet kernels for seismic velocities have long been established. In this study, we develop algorithms based on the finite-difference method for calculating Fréchet kernels for the quality factor Qμ and seismic boundary topography. Kernels for the quality factor can be obtained in a way similar to those for seismic velocities with the help of the Hilbert transform. The effects of seismic velocities and quality factor on either traveltime or amplitude are coupled. Kernels for boundary topography involve spatial gradient of the SGTs and they also exhibit interesting finite-frequency characteristics. Examples of quality factor and boundary topography kernels will be shown for a realistic model for the Taiwan region with three-dimensional velocity variation as well as surface and Moho discontinuity topography.

Mitogenic signaling pathways of growth factors can be distinguished by the involvement of pertussis toxin-sensitive guanosine triphosphate-binding protein and of protein kinase C.

PubMed Central

Nishizawa, N; Okano, Y; Chatani, Y; Amano, F; Tanaka, E; Nomoto, H; Nozawa, Y; Kohno, M

1990-01-01

We have examined the possible involvements of pertussis toxin (PT)-sensitive guanosine triphosphate (GTP)-binding protein (Gp) and protein kinase C (PKC) in the mitogenic signaling pathways of various growth factors by the use of PT-pretreated and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA)-pretreated mouse fibroblasts. Effects of PT pretreatment (inactivation of PT-sensitive Gp) and TPA pretreatment (depletion of PKC) on mitogen-induced DNA synthesis varied significantly and systematically in response to growth factors: mitogenic responses of cells to thrombin, bombesin, and bradykinin were almost completely abolished both in PT- and TPA-pretreated cells; responses to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vanadate were reduced to approximately 50% both in PT- and TPA-pretreated cells compared with native cells; response to basic fibroblast growth factor (bFGF) was not affected in PT-pretreated cells but was inhibited to some extent in TPA-pretreated cells. Thus, growth factors examined have been classified into three groups with regard to the involvements of PT-sensitive Gp and PKC in their signal transduction pathways. Binding of each growth factor to its receptor was not affected significantly by pretreatment of cells with PT or TPA. Inhibitory effects of PT and TPA pretreatment on each mitogen-induced DNA synthesis were not additive, suggesting that the functions of PT-sensitive Gp and PKC lie on an identical signal transduction pathway. Although all three groups of mitogens activated PKC, signaling of each growth factor depends to a varying extent on the function of PKC. Our results indicate that a single peptide growth factor such as EGF, PDGF, or bFGF acts through multiple signaling pathways to induce cell proliferation. Images PMID:2129194

Psychological factors associated with self-reported sensitivity to mobile phones.

PubMed

Rubin, G James; Cleare, Anthony J; Wessely, Simon

2008-01-01

Some people report symptoms associated with mobile phone use. A minority also report "electrosensitivity," experiencing symptoms following exposure to other electrical devices. Research suggests that electromagnetic fields do not trigger these symptoms. In this study, we examined the differences between these two "sensitive" groups and healthy controls. Fifty-two people who reported sensitivity to mobile phones, 19 people who reported sensitivity to mobile phones and "electrosensitivity," and 60 nonsensitive controls completed a questionnaire assessing the following: primary reason for using a mobile phone, psychological health, symptoms of depression, modern health worries (MHW), general health status, symptom severity, and the presence of other medically unexplained syndromes. Perceived sensitivity was associated with an increased likelihood of using a mobile phone predominantly for work (3% of controls, 13% of those sensitive to mobile phones, and 21% of those reporting "electrosensitivity") and greater MHW concerning radiation [mean (S.D.) on a scale of 1-5: 2.0 (1.0), 2.7 (0.9), and 4.0 (0.8), respectively]. Participants who reported "electrosensitivity" also experienced greater depression, greater worries about tainted food and toxic interventions, worse general health on almost every measure, and a greater number of other medically unexplained syndromes compared to participants from the other two groups. No group differences were observed with regards to psychiatric cases. The data illustrate that patients reporting "electrosensitivity" experience substantially worse health than either healthy individuals or people who report sensitivity to mobile phones but who do not adopt the label "electrosensitivity." Clinicians and researchers would be wise to pay greater attention to this subdivision.

Increased sensitivity to apoptosis induced by methotrexate is mediated by Jun N-terminal kinase

PubMed Central

Spurlock, Charles F.; Aune, Zachary T.; Tossberg, John T.; Collins, Patrick L.; Aune, Jessica P.; Huston, Joseph W.; Crooke, Philip S.; Olsen, Nancy J.; Aune, Thomas M.

2011-01-01

Objective Low-dose methotrexate [MTX] is an effective therapy for rheumatoid arthritis yet its mechanism of action is incompletely understood. Here, we explored induction of apoptosis by MTX. Methods We employed flow cytometry to assess changes in levels of intracellular proteins, reactive oxygen species [ROS], and apoptosis.Quantitative polymerase chain reaction was usedtoassess changes in transcript levels of select target genes in response to MTX. Results MTX does not directly induce apoptosis but rather ‘primes’ cells for markedly increased sensitivity to apoptosis via either mitochondrial or death receptor pathways by a Jun N-terminal kinase [JNK]-dependent mechanism. Increased sensitivity to apoptosis is mediated, at least in part, by MTX-dependent production of reactive oxygen species, JNK activation and JNK-dependent induction of genes whose protein products promote apoptosis. Supplementation with tetrahydrobiopterin blocks these methotrexate-induced effects. Subjects with rheumatoid arthritis on low-dose MTX therapy express elevated levels of the JNK-target gene, JUN. Conclusions Our results support a model whereby methotrexate inhibits reduction of dihydrobiopterin to tetrahydrobiopterin resulting in increased production of ROS, increased JNK activity and increased sensitivity to apoptosis. The finding of increased JUN levels in subjects with RA taking low-dose MTX supports the notion that this pathway is activated by MTX, in vivo, and may contribute to efficacy of MTX in inflammatory disease. PMID:21618198

A two-factor theory for concussion assessment using ImPACT: memory and speed.

PubMed

Schatz, Philip; Maerlender, Arthur

2013-12-01

We present the initial validation of a two-factor structure of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) using ImPACT composite scores and document the reliability and validity of this factor structure. Factor analyses were conducted for baseline (N = 21,537) and post-concussion (N = 560) data, yielding "Memory" (Verbal and Visual) and "Speed" (Visual Motor Speed and Reaction Time) Factors; inclusion of Total Symptom Scores resulted in a third discrete factor. Speed and Memory z-scores were calculated, and test-retest reliability (using intra-class correlation coefficients) at 1 month (0.88/0.81), 1 year (0.85/0.75), and 2 years (0.76/0.74) were higher than published data using Composite scores. Speed and Memory scores yielded 89% sensitivity and 70% specificity, which was higher than composites (80%/62%) and comparable with subscales (91%/69%). This emergent two-factor structure has improved test-retest reliability with no loss of sensitivity/specificity and may improve understanding and interpretability of ImPACT test results.

Pigment epithelium-derived factor, insulin sensitivity, and adiposity in polycystic ovary syndrome: impact of exercise training.

PubMed

Joham, Anju E; Teede, Helena J; Hutchison, Samantha K; Stepto, Nigel K; Harrison, Cheryce L; Strauss, Boyd J; Paul, Eldho; Watt, Matthew J

2012-12-01

Pigment epithelium-derived factor (PEDF) is upregulated in obese rodents and is involved in the development of insulin resistance (IR). We aim to explore the relationships between PEDF, adiposity, insulin sensitivity, and cardiovascular risk factors in obese women with polycystic ovary syndrome (PCOS) and weight-matched controls and to examine the impact of endurance exercise training on PEDF. This prospective cohort intervention study was based at a tertiary medical center. Twenty obese PCOS women and 14 non-PCOS weight-matched women were studied at baseline. PEDF, cardiometabolic markers, detailed body composition, and euglycemic-hyperinsulinemic clamps were performed and measures were repeated in 10 PCOS and 8 non-PCOS women following 12 weeks of intensified aerobic exercise. Mean glucose infusion rate (GIR) was 31.7% lower (P = 0.02) in PCOS compared to controls (175.6 ± 96.3 and 257.2 ± 64.3 mg.m(-2).min(-1)) at baseline, yet both PEDF and BMI were similar between groups. PEDF negatively correlated to GIR (r = -0.41, P = 0.03) and high-density lipoprotein (HDL) (r = -0.46, P = 0.01), and positively to cardiovascular risk factors, systolic (r = 0.41, P = 0.02) and diastolic blood pressure (r = 0.47, P = 0.01) and triglycerides (r = 0.49, P = 0.004). The correlation with GIR was not significant after adjusting for fat mass (P = 0.07). Exercise training maintained BMI and increased GIR in both groups; however, plasma PEDF was unchanged. In summary, PEDF is not elevated in PCOS, is not associated with IR when adjusted for fat mass, and is not reduced by endurance exercise training despite improved insulin sensitivity. PEDF was associated with cardiovascular risk factors, suggesting PEDF may be a marker of cardiovascular risk status.

Sec34p, a Protein Required for Vesicle Tethering to the Yeast Golgi Apparatus, Is in a Complex with Sec35p

PubMed Central

VanRheenen, Susan M.; Cao, Xiaochun; Sapperstein, Stephanie K.; Chiang, Elbert C.; Lupashin, Vladimir V.; Barlowe, Charles; Waters, M. Gerard

1999-01-01

A screen for mutants of Saccharomyces cerevisiae secretory pathway components previously yielded sec34, a mutant that accumulates numerous vesicles and fails to transport proteins from the ER to the Golgi complex at the restrictive temperature (Wuestehube, L.J., R. Duden, A. Eun, S. Hamamoto, P. Korn, R. Ram, and R. Schekman. 1996. Genetics. 142:393–406). We find that SEC34 encodes a novel protein of 93-kD, peripherally associated with membranes. The temperature-sensitive phenotype of sec34-2 is suppressed by the rab GTPase Ypt1p that functions early in the secretory pathway, or by the dominant form of the ER to Golgi complex target-SNARE (soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor)–associated protein Sly1p, Sly1-20p. Weaker suppression is evident upon overexpression of genes encoding the vesicle tethering factor Uso1p or the vesicle-SNAREs Sec22p, Bet1p, or Ykt6p. This genetic suppression profile is similar to that of sec35-1, a mutant allele of a gene encoding an ER to Golgi vesicle tethering factor and, like Sec35p, Sec34p is required in vitro for vesicle tethering. sec34-2 and sec35-1 display a synthetic lethal interaction, a genetic result explained by the finding that Sec34p and Sec35p can interact by two-hybrid analysis. Fractionation of yeast cytosol indicates that Sec34p and Sec35p exist in an ∼750-kD protein complex. Finally, we describe RUD3, a novel gene identified through a genetic screen for multicopy suppressors of a mutation in USO1, which suppresses the sec34-2 mutation as well. PMID:10562277

Small Heat Shock Proteins Are Novel Common Determinants of Alcohol and Nicotine Sensitivity in Caenorhabditis elegans

PubMed Central

Johnson, James R.; Rajamanoharan, Dayani; McCue, Hannah V.; Rankin, Kim

2016-01-01

Addiction to drugs is strongly determined by multiple genetic factors. Alcohol and nicotine produce distinct pharmacological effects within the nervous system through discrete molecular targets; yet, data from family and twin analyses support the existence of common genetic factors for addiction in general. The mechanisms underlying addiction, however, are poorly described and common genetic factors for alcohol and nicotine remain unidentified. We investigated the role that the heat shock transcription factor, HSF-1, and its downstream effectors played as common genetic modulators of sensitivity to addictive substances. Using Caenorhabditis elegans, an exemplary model organism with substance dose-dependent responses similar to mammals, we demonstrate that HSF-1 altered sensitivity to both alcohol and nicotine. Using a combination of a targeted RNAi screen of downstream factors and transgenic approaches we identified that these effects were contingent upon the constitutive neuronal expression of HSP-16.48, a small heat shock protein (HSP) homolog of human α-crystallin. Furthermore we demonstrated that the function of HSP-16.48 in drug sensitivity surprisingly was independent of chaperone activity during the heat shock stress response. Instead we identified a distinct domain within the N-terminal region of the HSP-16.48 protein that specified its function in comparison to related small HSPs. Our findings establish and characterize a novel genetic determinant underlying sensitivity to diverse addictive substances. PMID:26773049

High-sensitive factor I and C-reactive protein based biomarkers for coronary artery disease.

PubMed

Zhao, Qing; Du, Jian-Shi; Han, Dong-Mei; Ma, Ying

2014-01-01

An analysis of high-sensitive factor I and C-reactive proteins as biomarkers for coronary artery disease has been performed from 19 anticipated cohort studies that included 21,567 participants having no information about coronary artery disease. Besides, the clinical implications of statin therapy initiated due to assessment of factor I and C-reactive proteins have also been modeled during studies. The measure of risk discrimination (C-index) was increased (by 0.0101) as per the prognostic model for coronary artery disease with respect to sex, smoking status, age, blood pressure, total cholesterol level along with diabetic history characteristic parameters. The C-index was further raised by 0.0045 and 0.0053 when factor I and C-reactive proteins based information were added, respectively which finally predicted 10-year risk categories as: high (> 20%), medium (10% to < 20%), and low (< 10%) risks. We found 2,254 persons (among 15,000 adults (age ≥ 45 years)) would initially be classified as being at medium risk for coronary artery disease when only conventional risk factors were used as calculated risk. Besides, persons with a predicted risk of more than 20% as well as for persons suffering from other risk factors (i.e. diabetes), statin therapy was initiated (irrespective of their decade old predicted risk). We conclude that under current treatment guidelines assessment of factor I and C-reactive proteins levels (as biomarker) in people at medium risk for coronary artery disease could prevent one additional coronary artery disease risk over a period a decade for every 390-500 people screened.

Sensitivity analysis of a ground-water-flow model

USGS Publications Warehouse

Torak, Lynn J.; ,

1991-01-01

A sensitivity analysis was performed on 18 hydrological factors affecting steady-state groundwater flow in the Upper Floridan aquifer near Albany, southwestern Georgia. Computations were based on a calibrated, two-dimensional, finite-element digital model of the stream-aquifer system and the corresponding data inputs. Flow-system sensitivity was analyzed by computing water-level residuals obtained from simulations involving individual changes to each hydrological factor. Hydrological factors to which computed water levels were most sensitive were those that produced the largest change in the sum-of-squares of residuals for the smallest change in factor value. Plots of the sum-of-squares of residuals against multiplier or additive values that effect change in the hydrological factors are used to evaluate the influence of each factor on the simulated flow system. The shapes of these 'sensitivity curves' indicate the importance of each hydrological factor to the flow system. Because the sensitivity analysis can be performed during the preliminary phase of a water-resource investigation, it can be used to identify the types of hydrological data required to accurately characterize the flow system prior to collecting additional data or making management decisions.

Using Bayes factors for testing hypotheses about intervention effectiveness in addictions research.

PubMed

Beard, Emma; Dienes, Zoltan; Muirhead, Colin; West, Robert

2016-12-01

It has been proposed that more use should be made of Bayes factors in hypothesis testing in addiction research. Bayes factors are the ratios of the likelihood of a specified hypothesis (e.g. an intervention effect within a given range) to another hypothesis (e.g. no effect). They are particularly important for differentiating lack of strong evidence for an effect and evidence for lack of an effect. This paper reviewed randomized trials reported in Addiction between January and June 2013 to assess how far Bayes factors might improve the interpretation of the data. Seventy-five effect sizes and their standard errors were extracted from 12 trials. Seventy-three per cent (n = 55) of these were non-significant (i.e. P > 0.05). For each non-significant finding a Bayes factor was calculated using a population effect derived from previous research. In sensitivity analyses, a further two Bayes factors were calculated assuming clinically meaningful and plausible ranges around this population effect. Twenty per cent (n = 11) of the non-significant Bayes factors were < ⅓ and 3.6% (n = 2) were > 3. The other 76.4% (n = 42) of Bayes factors were between ⅓ and 3. Of these, 26 were in the direction of there being an effect (Bayes factor > 1 and < 3); 12 tended to favour the hypothesis of no effect (Bayes factor < 1 and > ⅓); and for four there was no evidence either way (Bayes factor = 1). In sensitivity analyses, 13.3% of Bayes Factors were < ⅓ (n = 20), 62.7% (n = 94) were between ⅓ and 3 and 24.0% (n = 36) were > 3, showing good concordance with the main results. Use of Bayes factors when analysing data from randomized trials of interventions in addiction research can provide important information that would lead to more precise conclusions than are obtained typically using currently prevailing methods. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Kinematic sensitivity of robot manipulators

NASA Technical Reports Server (NTRS)

Vuskovic, Marko I.

1989-01-01

Kinematic sensitivity vectors and matrices for open-loop, n degrees-of-freedom manipulators are derived. First-order sensitivity vectors are defined as partial derivatives of the manipulator's position and orientation with respect to its geometrical parameters. The four-parameter kinematic model is considered, as well as the five-parameter model in case of nominally parallel joint axes. Sensitivity vectors are expressed in terms of coordinate axes of manipulator frames. Second-order sensitivity vectors, the partial derivatives of first-order sensitivity vectors, are also considered. It is shown that second-order sensitivity vectors can be expressed as vector products of the first-order sensitivity vectors.

Landscape sensitivity in a dynamic environment

NASA Astrophysics Data System (ADS)

Lin, Jiun-Chuan; Jen, Chia-Horn

2010-05-01

Landscape sensitivity at different scales and topics is presented in this study. Methodological approach composed most of this paper. According to the environmental records in the south eastern Asia, the environment change is highly related with five factors, such as scale of influence area, background of environment characters, magnitude and frequency of events, thresholds of occurring hazards and influence by time factor. This paper tries to demonstrate above five points from historical and present data. It is found that landscape sensitivity is highly related to the degree of vulnerability of the land and the processes which put on the ground including human activities. The scale of sensitivity and evaluation of sensitivities is demonstrated in this paper by the data around east Asia. The methods of classification are mainly from the analysis of environmental data and the records of hazards. From the trend of rainfall records, rainfall intensity and change of temperature, the magnitude and frequency of earthquake, dust storm, days of draught, number of hazards, there are many coincidence on these factors with landscape sensitivities. In conclusion, the landscape sensitivities could be classified as four groups: physical stable, physical unstable, unstable, extremely unstable. This paper explain the difference.

Perinatal risk factors for asthma in children with allergic rhinitis and grass pollen sensitization.

PubMed

Yavuz, S Tolga; Siebert, Stephanie; Akin, Onur; Arslan, Mutluay; Civelek, Ersoy; Bagci, Soyhan

2018-05-01

Results of epidemiologic studies have determined several risk factors for asthma in school-age children. To examine whether parental and perinatal risk factors, along with infantile feeding patterns, were associated with asthma in children with grass pollen allergy and allergic rhinitis. We retrospectively analyzed the data of our cohort, which consisted of children with allergic rhinitis. Only children with grass pollen sensitization were enrolled. A detailed questionnaire regarding demographic features and perinatal events was given to the parents. A total of 293 children (200 boys [68.3%]; with median age, 10.2 years [interquartile range {IQR}, 7.4-13.0 years]) were included. A total of 109 children (37.2%) had accompanying asthma. The median age of onset of rhinitis symptoms was earlier (5.3 years [IQR, 4.0-8.0 years] versus 7.0 years [IQR, 5.0-10.0 years]; p = 0.001), histories of prematurity (16.7 versus 6.5%; p = 0.006), preeclampsia (5.5 versus 0%; p = 0.001), neonatal intensive care unit admission (15.1 versus 6.0%; p = 0.01), phototherapy (17.9 versus 7.1%; p = 0.004), early formula feeding (58.7 versus 41.2%; p = 0.006), and parental asthma (25.0 versus 11.4%; p = 0.002) were more frequent in children with asthma. Multivariate logistic regression analysis revealed prematurity (odds ratio [OR] 2.78 [95% confidence interval [CI],1.24-6.24]; p = 0.013), history of formula feeding (OR 1.81 [95% CI, 1.09-3.01]; p = 0.022), and parental asthma (OR 2.37 [95% CI, 1.22-4.63]; p = 0.011) were associated with asthma in school-age children with grass pollen-induced allergic rhinitis. Close monitoring of patients with these risk factors may help with an earlier diagnosis of asthma and prompt initiation of therapeutic interventions in children with allergic rhinitis and who were sensitized to grass pollen.

Revisiting Traditional Risk Factors for Rejection and Graft Loss after Kidney Transplantation

PubMed Central

Dunn, TB; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O. Goruroglu; Pruett, TL; Bray, RA; Gebel, HM; Matas, AJ

2011-01-01

Single antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and SAB testing of day of transplant serum as 1) unsensitized; PRA=0 (n= 178), 2) 3rd party sensitized; no DSA (n=363), or 3) donor sensitized; with DSA (n=46), and studied rejection rates, death censored graft survival (DCGS), and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p<0.0001), but not with PRA in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p<0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p=0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. PMID:21812918

Sensitivity Analysis of the USLE Soil Erodibility Factor to Its Determining Parameters

NASA Astrophysics Data System (ADS)

Mitova, Milena; Rousseva, Svetla

2014-05-01

Soil erosion is recognized as one of the most serious soil threats worldwide. Soil erosion prediction is the first step in soil conservation planning. The Universal Soil Loss Equation (USLE) is one of the most widely used models for soil erosion predictions. One of the five USLE predictors is the soil erodibility factor (K-factor), which evaluates the impact of soil characteristics on soil erosion rates. Soil erodibility nomograph defines K-factor depending on soil characteristics, such as: particle size distribution (fractions finer that 0.002 mm and from 0.1 to 0.002 mm), organic matter content, soil structure and soil profile water permeability. Identifying the soil characteristics, which mostly influence the K-factor would give an opportunity to control the soil loss through erosion by controlling the parameters, which reduce the K-factor value. The aim of the report is to present the results of analysis of the relative weight of these soil characteristics in the K-factor values. The relative impact of the soil characteristics on K-factor was studied through a series of statistical analyses of data from the geographic database for soil erosion risk assessments in Bulgaria. Degree of correlation between K-factor values and the parameters that determine it was studied by correlation analysis. The sensitivity of the K-factor was determined by studying the variance of each parameter within the range between minimum and maximum possible values considering average value of the other factors. Normalizing transformation of data sets was applied because of the different dimensions and the orders of variation of the values of the various parameters. The results show that the content of particles finer than 0.002 mm has the most significant relative impact on the soil erodibility, followed by the content of particles with size from 0.1 mm to 0.002 mm, the class of the water permeability of the soil profile, the content of organic matter and the aggregation class. The

Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.

PubMed

Biedermann, J S; van den Besselaar, A M H P; de Maat, M P M; Leebeek, F W G; Kruip, M J H A

2017-03-01

Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL -1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL -1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences

Estimating the sensitivity of passive surveillance for HPAI H5N1 in Bayelsa state, Nigeria.

PubMed

Ojimelukwe, Agatha E; Prakarnkamanant, Apisit; Rushton, Jonathan

2016-07-01

This study identified characteristics of poultry farming with a focus on practices that affect the detection of HPAI; and estimated the system sensitivity of passive surveillance for HPAI H5N1 in commercial and backyard chicken farms in Bayelsa-State, Nigeria. Field studies were carried out in Yenegoa and Ogbia local government areas in Bayelsa state. Willingness to report HPAI was highest in commercial poultry farms (13/13) than in Backyard farms (8/13). Poor means of dead bird disposal was common to both commercial and backyard farms. Administering some form of treatment to sick birds without prior consultation with a professional was higher in backyard farms (8/13) than in commercial farms (4/13). Consumption of sick birds was reported in 4/13 backyard farms and sale of dead birds was recorded in one commercial farm. The sensitivity of passive surveillance for HPAI was assessed using scenario tree modelling. A scenario tree model was developed and applied to estimate the sensitivity, i.e. the probability of detecting one or more infected chicken farms in Bayelsa state at different levels of disease prevalence. The model showed a median sensitivity of 100%, 67% and 23% for detecting HPAI by passive surveillance at a disease prevalence of 0.1%, a minimum of 10 and 3 infected poultry farms respectively. Passive surveillance system sensitivity at a design prevalence of 10 infected farms is increasable up to 86% when the disease detection in backyard chicken farms is enhanced. Copyright © 2016 Elsevier B.V. All rights reserved.

A sensitive and efficient method for determination of N-acetylhexosamines and N-acetylneuraminic acid in breast milk and milk-based products by high-performance liquid chromatography via UV detection and mass spectrometry identification.

PubMed

Chuanxiang, Wu; Lian, Xia; Lijie, Liu; Fengli, Qu; Zhiwei, Sun; Xianen, Zhao; Jinmao, You

2016-02-01

A sensitive and efficient method of high performance liquid chromatography using 1-(2-naphthyl)-3-methyl-5-pyrazolone (NMP) as pre-column derivatization reagent coupled with UV detection (HPLC-UV) and online mass spectrometry identification was established for determination of the most common N-Acetylhexosamines (N-acetyl-d-glucosamine (GlcNAc) and N-acetyl-d-galactosamine (GalNAc)) and N-acetylneuraminic acid (Neu5Ac). In order to obtain the highest liberation level of the three monosaccharides without destruction of Neu5Ac or conversion of GlcNAc/GalNAc to GlcN/GalN in the hydrolysis procedure, the pivotal parameters affecting the liberation of N-acetylhexosamines/Neu5Ac from sample were investigated with response surface methodology (RSM). Under the optimized condition, maximum yield was obtained. The effects of key parameters on derivatization, separation and detection were also investigated. At optimized conditions, three monosaccharides were labeled fast and entirely, and all derivatives exhibited a good baseline resolution and high detection sensitivity. The developed method was linear over the calibration range 0.25-12μM, with R(2)>0.9991. The detection limits of the method were between 0.48 and 2.01pmol. Intra- and inter-day precisions for the three monosaccharides (GlcNAc, GalNAc and Neu5Ac) were found to be in the range of 3.07-4.02% and 3.69-4.67%, respectively. Individual monosaccharide recovery from spiked milk was in the range of 81%-97%. The sensitivity of the method, the facility of the derivatization procedure and the reliability of the hydrolysis conditions suggest the proposed method has a high potential for utilization in routine trace N-acetylhexosamines and Neu5Ac analysis in biological samples. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel line immunoassay based on recombinant virulence factors enables highly specific and sensitive serologic diagnosis of Helicobacter pylori infection.

PubMed

Formichella, Luca; Romberg, Laura; Bolz, Christian; Vieth, Michael; Geppert, Michael; Göttner, Gereon; Nölting, Christina; Walter, Dirk; Schepp, Wolfgang; Schneider, Arne; Ulm, Kurt; Wolf, Petra; Busch, Dirk H; Soutschek, Erwin; Gerhard, Markus

2013-11-01

Helicobacter pylori colonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome. H. pylori virulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to important H. pylori virulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed in Escherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) were H. pylori negative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), the recomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, the recomLine assay provides a valuable tool for the diagnosis of H. pylori infection.

Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China.

PubMed

Li, Jing; Rao, Yuhan; Sun, Qinglan; Wu, Xiaoxu; Jin, Jiao; Bi, Yuhai; Chen, Jin; Lei, Fumin; Liu, Qiyong; Duan, Ziyuan; Ma, Juncai; Gao, George F; Liu, Di; Liu, Wenjun

2015-12-11

Human influenza infections display a strongly seasonal pattern. However, whether H7N9 and H5N1 infections correlate with climate factors has not been examined. Here, we analyzed 350 cases of H7N9 infection and 47 cases of H5N1 infection. The spatial characteristics of these cases revealed that H5N1 infections mainly occurred in the South, Middle, and Northwest of China, while the occurrence of H7N9 was concentrated in coastal areas of East and South of China. Aside from spatial-temporal characteristics, the most adaptive meteorological conditions for the occurrence of human infections by these two viral subtypes were different. We found that H7N9 infections correlate with climate factors, especially temperature (TEM) and relative humidity (RHU), while H5N1 infections correlate with TEM and atmospheric pressure (PRS). Hence, we propose a risky window (TEM 4-14 °C and RHU 65-95%) for H7N9 infection and (TEM 2-22 °C and PRS 980-1025 kPa) for H5N1 infection. Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks.

Open-Gated pH Sensor Fabricated on an Undoped-AlGaN/GaN HEMT Structure

PubMed Central

Abidin, Mastura Shafinaz Zainal; Hashim, Abdul Manaf; Sharifabad, Maneea Eizadi; Rahman, Shaharin Fadzli Abd; Sadoh, Taizoh

2011-01-01

The sensing responses in aqueous solution of an open-gated pH sensor fabricated on an AlGaN/GaN high-electron-mobility-transistor (HEMT) structure are investigated. Under air-exposed ambient conditions, the open-gated undoped AlGaN/GaN HEMT only shows the presence of a linear current region. This seems to show that very low Fermi level pinning by surface states exists in the undoped AlGaN/GaN sample. In aqueous solution, typical current-voltage (I-V) characteristics with reasonably good gate controllability are observed, showing that the potential of the AlGaN surface at the open-gated area is effectively controlled via aqueous solution by the Ag/AgCl gate electrode. The open-gated undoped AlGaN/GaN HEMT structure is capable of distinguishing pH level in aqueous electrolytes and exhibits linear sensitivity, where high sensitivity of 1.9 mA/pH or 3.88 mA/mm/pH at drain-source voltage, VDS = 5 V is obtained. Due to the large leakage current where it increases with the negative gate voltage, Nernstian like sensitivity cannot be determined as commonly reported in the literature. This large leakage current may be caused by the technical factors rather than any characteristics of the devices. Surprisingly, although there are some imperfections in the device preparation and measurement, the fabricated devices work very well in distinguishing the pH levels. Suppression of current leakage by improving the device preparation is likely needed to improve the device performance. The fabricated device is expected to be suitable for pH sensing applications. PMID:22163786

Validation of a Brazilian version of the moral sensitivity questionnaire.

PubMed

Dalla Nora, Carlise R; Zoboli, Elma Lcp; Vieira, Margarida M

2017-01-01

Moral sensitivity has been identified as a foundational component of ethical action. Diminished or absent moral sensitivity can result in deficient care. In this context, assessing moral sensitivity is imperative for designing interventions to facilitate ethical practice and ensure that nurses make appropriate decisions. The main purpose of this study was to validate a scale for examining the moral sensitivity of Brazilian nurses. A pre-existing scale, the Moral Sensitivity Questionnaire, which was developed by Lützén, was used after the deletion of three items. The reliability and validity of the scale were examined using Cronbach's alpha and factor analysis, respectively. Participants and research context: Overall, 316 nurses from Rio Grande do Sul, Brazil, participated in the study. Ethical considerations: This study was approved by the Ethics Committee of Research of the Nursing School of the University of São Paulo. The Moral Sensitivity Questionnaire contained 27 items that were distributed across four dimensions: interpersonal orientation, professional knowledge, moral conflict and moral meaning. The questionnaire accounted for 55.8% of the total variance, with Cronbach's alpha of 0.82. The mean score for moral sensitivity was 4.45 (out of 7). The results of this study were compared with studies from other countries to examine the structure and implications of the moral sensitivity of nurses in Brazil. The Moral Sensitivity Questionnaire is an appropriate tool for examining the moral sensitivity of Brazilian nurses.

Qa-SNAREs localized to the trans-Golgi network regulate multiple transport pathways and extracellular disease resistance in plants

PubMed Central

Uemura, Tomohiro; Kim, Hyeran; Saito, Chieko; Ebine, Kazuo; Ueda, Takashi; Schulze-Lefert, Paul; Nakano, Akihiko

2012-01-01

In all eukaryotic cells, a membrane-trafficking system connects the post-Golgi organelles, such as the trans-Golgi network (TGN), endosomes, vacuoles, and the plasma membrane. This complex network plays critical roles in several higher-order functions in multicellular organisms. The TGN, one of the important organelles for protein transport in the post-Golgi network, functions as a sorting station, where cargo proteins are directed to the appropriate post-Golgi compartments. Unlike its roles in animal and yeast cells, the TGN has also been reported to function like early endosomal compartments in plant cells. However, the physiological roles of the TGN functions in plants are not understood. Here, we report a study of the SYP4 group (SYP41, SYP42, and SYP43), which represents the plant orthologs of the Tlg2/syntaxin16 Qa-SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) that localizes on the TGN in yeast and animal cells. The SYP4 group regulates the secretory and vacuolar transport pathways in the post-Golgi network and maintains the morphology of the Golgi apparatus and TGN. Consistent with a secretory role, SYP4 proteins are required for extracellular resistance responses to a fungal pathogen. We also reveal a plant cell-specific higher-order role of the SYP4 group in the protection of chloroplasts from salicylic acid-dependent biotic stress. PMID:22307646

Selective Regulation of Maize Plasma Membrane Aquaporin Trafficking and Activity by the SNARE SYP121[W

PubMed Central

Besserer, Arnaud; Burnotte, Emeline; Bienert, Gerd Patrick; Chevalier, Adrien S.; Errachid, Abdelmounaim; Grefen, Christopher; Blatt, Michael R.; Chaumont, François

2012-01-01

Plasma membrane intrinsic proteins (PIPs) are aquaporins facilitating the diffusion of water through the cell membrane. We previously showed that the traffic of the maize (Zea mays) PIP2;5 to the plasma membrane is dependent on the endoplasmic reticulum diacidic export motif. Here, we report that the post-Golgi traffic and water channel activity of PIP2;5 are regulated by the SNARE (for soluble N-ethylmaleimide-sensitive factor protein attachment protein receptor) SYP121, a plasma membrane resident syntaxin involved in vesicle traffic, signaling, and regulation of K+ channels. We demonstrate that the expression of the dominant-negative SYP121-Sp2 fragment in maize mesophyll protoplasts or epidermal cells leads to a decrease in the delivery of PIP2;5 to the plasma membrane. Protoplast and oocyte swelling assays showed that PIP2;5 water channel activity is negatively affected by SYP121-Sp2. A combination of in vitro (copurification assays) and in vivo (bimolecular fluorescence complementation, Förster resonance energy transfer, and yeast split-ubiquitin) approaches allowed us to demonstrate that SYP121 and PIP2;5 physically interact. Together with previous data demonstrating the role of SYP121 in regulating K+ channel trafficking and activity, these results suggest that SYP121 SNARE contributes to the regulation of the cell osmotic homeostasis. PMID:22942383

Selective regulation of maize plasma membrane aquaporin trafficking and activity by the SNARE SYP121.

PubMed

Besserer, Arnaud; Burnotte, Emeline; Bienert, Gerd Patrick; Chevalier, Adrien S; Errachid, Abdelmounaim; Grefen, Christopher; Blatt, Michael R; Chaumont, François

2012-08-01

Plasma membrane intrinsic proteins (PIPs) are aquaporins facilitating the diffusion of water through the cell membrane. We previously showed that the traffic of the maize (Zea mays) PIP2;5 to the plasma membrane is dependent on the endoplasmic reticulum diacidic export motif. Here, we report that the post-Golgi traffic and water channel activity of PIP2;5 are regulated by the SNARE (for soluble N-ethylmaleimide-sensitive factor protein attachment protein receptor) SYP121, a plasma membrane resident syntaxin involved in vesicle traffic, signaling, and regulation of K(+) channels. We demonstrate that the expression of the dominant-negative SYP121-Sp2 fragment in maize mesophyll protoplasts or epidermal cells leads to a decrease in the delivery of PIP2;5 to the plasma membrane. Protoplast and oocyte swelling assays showed that PIP2;5 water channel activity is negatively affected by SYP121-Sp2. A combination of in vitro (copurification assays) and in vivo (bimolecular fluorescence complementation, Förster resonance energy transfer, and yeast split-ubiquitin) approaches allowed us to demonstrate that SYP121 and PIP2;5 physically interact. Together with previous data demonstrating the role of SYP121 in regulating K(+) channel trafficking and activity, these results suggest that SYP121 SNARE contributes to the regulation of the cell osmotic homeostasis.

Developmental and diurnal expression of the synaptosomal-associated protein 25 (Snap25) in the rat pineal gland.

PubMed

Karlsen, Anna S; Rath, Martin F; Rohde, Kristian; Toft, Trine; Møller, Morten

2013-06-01

Snap25 (synaptosomal-associated protein) is a 25 kDa protein, belonging to the SNARE-family (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) of proteins, essential for synaptic and secretory vesicle exocytosis. Snap25 has by immunohistochemistry been demonstrated in the rat pineal gland but the biological importance of this is unknown. In this study, we demonstrate a high expression of mRNA encoding Snap25 in all parts of the rat pineal complex, the superficial-, and deep-pineal gland, as well as in the pineal stalk. Snap25 showed a low pineal expression during embryonic stages with a strong increase in expression levels just after birth. The expression showed no day/night variations. Neither removal of the sympathetic input to the pineal gland by superior cervical ganglionectomy nor bilateral decentralization of the superior cervical ganglia significantly affected the expression of Snap25 in the gland. The pineal expression levels of Snap25 were not changed following intraperitoneal injection of isoproterenol. The strong expression of Snap25 in the pineal gland suggests the presence of secretory granules and microvesicles in the rat pinealocyte supporting the concept of a vesicular release. At the transcriptional level, this Snap25-based release mechanism does not exhibit any diurnal rhythmicity and is regulated independently of the sympathetic nervous input to the gland.

A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

NASA Astrophysics Data System (ADS)

D'Agostino, Massimo; Risselada, Herre Jelger; Lürick, Anna; Ungermann, Christian; Mayer, Andreas

2017-11-01

Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.

Prolonged breastfeeding and delayed introduction of whole cow's milk into the diet are factors associated with egg sensitization: A matched case-control study.

PubMed

Bedolla-Barajas, M; Morales-Romero, J; Gaxiola-Arredondo, B Y; Alcalá-Padilla, G; Romero-Velarde, E

2018-05-05

Both breastfeeding and the moment at which introduction to solid food occurs have been associated with food allergy. To evaluate whether prolonged breastfeeding and the delayed introduction of whole cow's milk into an infant's diet are factors that can be associated with egg sensitization. This was a hospital-based case-control study, matched by age and sex: each study group comprised 97 atopic children. Additionally, logistic regression was used to identify the factors associated with egg protein sensitization. The most common type of allergic disease among both groups was allergic rhinitis. After adjusting for possible confounding variables, a delayed introduction to whole cow's milk decreased the odds of egg protein sensitization; OR=0.16 (95% CI: 0.07-0.36, p<0.0001). Notably, breastfeeding during the first six months of life, regardless of whether it was the only milk an infant drank, increased the risk for sensitization to chicken eggs; OR=5.54 (95% CI: 2.41-12.7, p<0.0001). Prolonged breastfeeding, regardless of whether it was the only milk an infant drank, greatly increased the risk of egg sensitization. Interestingly, a delayed introduction to whole cow's milk was associated with a reduced possibility of becoming sensitized to eggs. Further studies are required to elucidate these findings. Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

PubMed Central

Merrill, Liana; Malley, Susan

2013-01-01

Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1–4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. PMID:23657640

The role of chronic psychosocial stress in explaining racial differences in stress reactivity and pain sensitivity

PubMed Central

Gordon, Jennifer L.; Johnson, Jacqueline; Nau, Samantha; Mechlin, Beth; Girdler, Susan S.

2016-01-01

Objective To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. Methods Participants included 133 AA and non-Hispanic White (nHW) individuals (mean (SD) age = 37 (9)) matched for age, sex and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. Results Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g. r = −.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. Conclusion Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs’ increased pain sensitivity in laboratory settings. PMID:27669431

The Role of Chronic Psychosocial Stress in Explaining Racial Differences in Stress Reactivity and Pain Sensitivity.

PubMed

Gordon, Jennifer L; Johnson, Jacqueline; Nau, Samantha; Mechlin, Beth; Girdler, Susan S

To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. Participants included 133 AA and non-Hispanic white (nHW) individuals (mean [SD] age, 37 [9]) matched for age, sex, and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g., r = -.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs' increased pain sensitivity in laboratory settings.

Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha.

PubMed

Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

1995-09-15

Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogenesis of asthma; however, little is known of its direct effect on smooth muscle reactivity. We investigated the effect of TNF alpha on the responsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased responsiveness to electrical field stimulation (113 +/- 8, 110 +/- 4 and 112 +/- 2% respectively) compared to control (99 +/- 2%) (P < 0.05, n = 6). Responses were not increased in sensitized tissue (101 +/- 3% versus 105 +/- 5%, n = 3, P > 0.05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%, n = 3, P = 0.38). These results show that TNF alpha causes an increase in responsiveness of human bronchial tissue and that this occurs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiveness.

GM(1,N) method for the prediction of anaerobic digestion system and sensitivity analysis of influential factors.

PubMed

Ren, Jingzheng

2018-01-01

Anaerobic digestion process has been recognized as a promising way for waste treatment and energy recovery in a sustainable way. Modelling of anaerobic digestion system is significantly important for effectively and accurately controlling, adjusting, and predicting the system for higher methane yield. The GM(1,N) approach which does not need the mechanism or a large number of samples was employed to model the anaerobic digestion system to predict methane yield. In order to illustrate the proposed model, an illustrative case about anaerobic digestion of municipal solid waste for methane yield was studied, and the results demonstrate that GM(1,N) model can effectively simulate anaerobic digestion system at the cases of poor information with less computational expense. Copyright © 2017 Elsevier Ltd. All rights reserved.

Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines.

PubMed

Witta, Samir E; Gemmill, Robert M; Hirsch, Fred R; Coldren, Christopher D; Hedman, Karla; Ravdel, Larisa; Helfrich, Barbara; Dziadziuszko, Rafal; Chan, Daniel C; Sugita, Michio; Chan, Zeng; Baron, Anna; Franklin, Wilbur; Drabkin, Harry A; Girard, Luc; Gazdar, Adi F; Minna, John D; Bunn, Paul A

2006-01-15

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, produce 9% to 27% response rates in NSCLC patients. E-Cadherin, a calcium-dependent adhesion molecule, plays an important role in NSCLC prognosis and progression, and interacts with EGFR. The zinc finger transcriptional repressor, ZEB1, inhibits E-cadherin expression by recruiting histone deacetylases (HDAC). We identified a significant correlation between sensitivity to gefitinib and expression of E-cadherin, and ZEB1, suggesting their predictive value for responsiveness to EGFR-tyrosine kinase inhibitors. E-Cadherin transfection into a gefitinib-resistant line increased its sensitivity to gefitinib. Pretreating resistant cell lines with the HDAC inhibitor, MS-275, induced E-cadherin along with EGFR and led to a growth-inhibitory and apoptotic effect of gefitinib similar to that in gefitinib-sensitive NSCLC cell lines including those harboring EGFR mutations. Thus, combined HDAC inhibitor and gefitinib treatment represents a novel pharmacologic strategy for overcoming resistance to EGFR inhibitors in patients with lung cancer.

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin in the evaluation of acute chest pain of uncertain etiology. A PITAGORAS substudy.

PubMed

Sanchis, Juan; Bardají, Alfredo; Bosch, Xavier; Loma-Osorio, Pablo; Marín, Francisco; Sánchez, Pedro L; Calvo, Francisco; Avanzas, Pablo; Hernández, Carolina; Serrano, Silvia; Carratalá, Arturo; Barrabés, José A

2013-07-01

High-sensitivity troponin assays have improved the diagnosis of acute coronary syndrome in patients presenting with chest pain and normal troponin levels as measured by conventional assays. Our aim was to investigate whether N-terminal pro-brain natriuretic peptide provides additional information to troponin determination in these patients. A total of 398 patients, included in the PITAGORAS study, presenting to the emergency department with chest pain and normal troponin levels as measured by conventional assay in 2 serial samples (on arrival and 6 h to 8h later) were studied. The samples were also analyzed in a central laboratory for high-sensitivity troponin T (both samples) and for N-terminal pro-brain natriuretic peptide (second sample). The endpoints were diagnosis of acute coronary syndrome and the composite endpoint of in-hospital revascularization or a 30-day cardiac event. Acute coronary syndrome was adjudicated to 79 patients (20%) and the composite endpoint to 59 (15%). When the N-terminal pro-brain natriuretic peptide quartile increased, the diagnosis of acute coronary syndrome also increased (12%, 16%, 23% and 29%; P=.01), as did the risk of the composite endpoint (6%, 13%, 16% and 24%; P=.004). N-terminal pro-brain natriuretic peptide elevation (>125ng/L) was associated with both endpoints (relative risk= 2.0; 95% confidence interval, 1.2-3.3; P=.02; relative risk=2.4; 95% confidence interval, 1.4-4.2; P=.004). However, in the multivariable models adjusted by clinical and electrocardiographic data, a predictive value was found for high-sensitivity T troponin but not for N-terminal pro-brain natriuretic peptide. In low-risk patients with chest pain of uncertain etiology evaluated using high-sensitivity T troponin, N-terminal pro-brain natriuretic peptide does not contribute additional predictive value to diagnosis or the prediction of short-term outcomes. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights

Ethnicity is associated with alterations in oxytocin relationships to pain sensitivity in women

PubMed Central

Grewen, Karen M.; Light, Kathleen C.; Mechlin, Beth; Girdler, Susan S.

2015-01-01

It is well established that African Americans (AA) experience greater pain associated with a variety of clinical conditions, and greater pain sensitivity to experimental pain tasks relative to non-Hispanic Whites (W). Notably, African Americans do not show the same relationships involving endogenous pain regulatory mechanisms and pain sensitivity documented in Caucasians, including positive associations between blood pressure, norepinephrine, cortisol and greater pain tolerance. Objectives The purpose of this study was to examine the relationship between plasma oxytocin (OT) and pain sensitivity and to explore the relation of OT to other factors known to influence pain perception. Design OT concentration and sensitivity to ischemic, cold pressor, and thermal pain tasks were assessed in African American (n=25) and non-Hispanic White (n=23) pre-menopausal women. Results African American women demonstrated significantly lower pain tolerance across tasks compared with Whites (F1,46 =6.31, p=0.0156) and also exhibited lower plasma OT levels (AA: 3.90, W: 7.05 pg/mL; p=0.0014). Greater OT levels were correlated with greater tolerance to ischemic pain (r=0.36, p=0.013) and accounted for a marginally significant portion of the ethnic difference in ischemic pain tolerance (B=+0.29, p=0.06). Greater OT was also correlated with greater tolerance of cold pressor pain (r=0.31, p=0.03); however, this association was no longer seen after the variance due to ethnicity was accounted for. Conclusion These data suggest that reduced oxytocinergic function may be one of multiple biological factors contributing to the greater sensitivity to experimental ischemic pain, and to the greater burden of some types of clinical pain experienced by African Americans compared with Whites. PMID:18568974

Purification and characterization of an amidohydrolase for N4-long-chain fatty acyl derivatives of 1-beta-D-arabinofuranosylcytosine from mouse liver microsomes.

PubMed

Hori, K; Tsuruo, T; Tsukagoshi, S; Sakurai, Y

1984-03-01

N4-Long-chain fatty acyl-1-beta-D-arabinofuranosylcytosine amidohydrolase, a metabolizing enzyme for N4-acyl derivatives of 1-beta-D-arabinofuranosylcytosine with long-chain fatty acids, was purified from mouse liver microsomes. The purification was accomplished by solubilization of liver microsomes with Triton X-100, diethylaminoethyl cellulose chromatography, gel filtrations, hydroxyapatite chromatography, and concanavalin A:Sepharose chromatography. On sodium dodecyl sulfate:polyacrylamide gel electrophoresis, the purified enzyme preparation produced a single protein band with a molecular weight of 54,000. The enzyme had an optimal pH of 9.0, and the Michaelis constant for N4-palmitoyl-1-beta-D-arabinofuranosylcytosine was 67 microM. The thiols such as dithiothreitol or 2-mercaptoethanol stabilized the enzyme and stimulated its activity. p-Chloromercuribenzoate, N-ethylmaleimide, diisopropylfluorophosphate, and phenylmethylsulfonyl fluoride strongly inhibited the reaction. Bovine serum albumin markedly stimulated the enzyme activity, whereas detergents such as Triton X-100, deoxycholate, and sodium dodecyl sulfate had little effect. The enzyme did not require monovalent or divalent cations. Among the series of N4-acyl derivatives of 1-beta-D-arabinofuranosylcytosine with different chain lengths of acyl residues, the purified enzyme preferentially hydrolyzed the derivatives with long-chain fatty acids (C12 to C18), and N4-palmitoyl-1-beta-D-arabinofuranosylcytosine was the most susceptible. The purified enzyme was inactive on various N-acylamino acids, amides, oligopeptides, proteins, N-acylsphingosines (ceramides), triglyceride, lecithin, and lysolecithin. These results suggest that N4-long-chain fatty acyl-1-beta-D-arabinofuranosylcytosine amidohydrolase may be a new type of linear amidase.

Two classes of ouabain binding sites in ferret heart and two forms of Na+-K+-ATPase

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

Ng, Y.C.; Akera, T.

1987-05-01

In partially purified Na+-K+-adenosinetriphosphatase (ATPase) obtained from ferret heart, ouabain produced a monophasic inhibition curve; however, the curve spanned over 5 logarithmic units, indicating the presence of more than one classes of enzyme. (/sup 3/H)ouabain binding studies revealed high-and low-affinity binding sites in approximately equal abundance, with apparent dissociation constants of 10 and 230 nM, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of phosphoenzyme formed from (gamma-/sup 32/P)ATP showed two distinct K+-sensitive bands of approximately 100,000 molecular weight. Phosphoenzyme formation from the high-molecular-weight alpha(+) form was selectively inhibited by N-ethylmaleimide. Ouabain caused a 50% inhibition of phosphorylation of the alpha(+) formmore » at 40 nM and the lower-molecular-weight alpha form at 300 nM. In papillary muscle preparations, 1-30 nM ouabain produced a modest positive inotropic effect that reached an apparent plateau at 30 nM. Further increases in ouabain concentrations, however, produced additional and prominent inotropic effects at 0.1-10 microM. These results indicate for the first time in cardiac muscle that the high- and low-affinity ouabain binding sites are associated with the alpha(+) and alpha forms of the Na+-K+-ATPase, respectively, and that binding of ouabain to either of these sites causes enzyme inhibition and the positive inotropic effect.« less

Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis.

PubMed

Schlievert, Patrick M; Strandberg, Kristi L; Lin, Ying-Chi; Peterson, Marnie L; Leung, Donald Y M

2010-01-01

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have emerged as serious health threats in the last 15 years. They are associated with large numbers of atopic dermatitis skin and soft tissue infections, but when they originate from skin and mucous membranes, have the capacity to produce sepsis and highly fatal pulmonary infections characterized as necrotizing pneumonia, purpura fulminans, and postviral toxic shock syndrome. This review is a discussion of the emergence of 3 major CA-MRSA organisms, designated CA-MRSA USA400, followed by USA300, and most recently USA200. CA-MRSA USA300 and USA400 isolates and their methicillin-sensitive counterparts (community-associated methicillin-sensitive S aureus) typically produce highly inflammatory cytolysins alpha-toxin, gamma-toxin, delta-toxin (as representative of the phenol soluble modulin family of cytolysins), and Panton Valentine leukocidin. USA300 isolates produce the superantigens enterotoxin-like Q and a highly pyrogenic deletion variant of toxic shock syndrome toxin 1 (TSST-1), whereas USA400 isolates produce the superantigens staphylococcal enterotoxin B or staphylococcal enterotoxin C. USA200 CA-MRSA isolates produce small amounts of cytolysins but produce high levels of TSST-1. In contrast, their methicillin-sensitive S aureus counterparts produce various cytolysins, apparently in part dependent on the niche occupied in the host and levels of TSST-1 expressed. Significant differences seen in production of secreted virulence factors by CA-MRSA versus hospital-associated methicillin-resistant S aureus and community-associated methicillin-sensitive S aureus strains appear to be a result of the need to specialize as the result of energy drains from both virulence factor production and methicillin resistance. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Coexpression of alpha and beta subunits of the rod cyclic GMP-gated channel restores native sensitivity to cyclic AMP: role of D604/N1201.

PubMed Central

Pagès, F; Ildefonse, M; Ragno, M; Crouzy, S; Bennett, N

2000-01-01

Coexpression of the betawt and alphawt subunits of the bovine rod channel restores two characteristics of the native channels: higher sensitivity to cAMP and potentiation of cGMP-induced currents by low cAMP concentrations. To test whether the increased sensitivity to cAMP is due to the uncharged nature of the asparagine residue (N1201) situated in place of aspartate D604 in the beta subunit as previously suggested (, Neuron. 15:619-625), we compared currents from wild-type (alphawt and alphawt/betawt) and from mutated channels (alphaD604N, alphaD604N/betawt, and alphawt/betaN1201D). The results show that the sensitivity to cAMP and cAMP potentiation is partly but not entirely determined by the charge of residue 1201 in the beta subunit. The D604N mutation in the alpha subunit and, to a lesser extent, coexpression of the betawt subunit with the alphawt subunit reduce the open probability for cGMP compared to that of the alphawt channel. Interpretation of the data with the MWC allosteric model (model of Monod, Wyman, Changeux;, J. Mol. Biol. 12:88-118) suggests that the D604N mutation in the alpha subunits and coassembly of alpha and beta subunits alter the free energy of gating by cAMP more than that of cAMP binding. PMID:10692312

Incentive Sensitivity as a Behavioral Marker of Clinical Remission From Major Depressive Episode.

PubMed

Mauras, Thomas; Masson, Marc; Fossati, Philippe; Pessiglione, Mathias

2016-06-01

Reduction of goal-directed behaviors is frequently observed in depression and may be linked to dysfunction of incentive motivation process. To investigate whether incentive sensitivity could constitute a behavioral marker of clinical remission in major depression. A handgrip force measurement device was employed to assess the impact of incentive motivation and emotional manipulation on the effort produced by remitted patients (n = 20) compared to matched depressed patients (n = 22) and healthy controls (n = 26). Depressed and remitted patients fulfilled the major depressive disorder DSM-IV criteria for current episode and remission state, respectively. The study was performed between March and July 2013. Relative to patients with acute depression, patients after remission retrieved a normal sensitivity to incentives (t1,40 = 4.18, P < 1.5 × 10-4), but relative to healthy controls, they kept an abnormally high susceptibility to emotional arousal (t1,44 = 2.4, P = .02). Normalization of incentive sensitivity exhibited in the behavioral test was associated with improvement of apathy measured on the clinical scale. Using a simple behavioral paradigm at patients' bedside, we could identify the factors influencing effort production, so as to discriminate remitted patients from both depressed patients and healthy controls. © Copyright 2016 Physicians Postgraduate Press, Inc.

Warming and drought reduce temperature sensitivity of nitrogen transformations.

PubMed

Novem Auyeung, Dolaporn S; Suseela, Vidya; Dukes, Jeffrey S

2013-02-01

Shifts in nitrogen (N) mineralization and nitrification rates due to global changes can influence nutrient availability, which can affect terrestrial productivity and climate change feedbacks. While many single-factor studies have examined the effects of environmental changes on N mineralization and nitrification, few have examined these effects in a multifactor context or recorded how these effects vary seasonally. In an old-field ecosystem in Massachusetts, USA, we investigated the combined effects of four levels of warming (up to 4 °C) and three levels of precipitation (drought, ambient, and wet) on net N mineralization, net nitrification, and potential nitrification. We also examined the treatment effects on the temperature sensitivity of net N mineralization and net nitrification and on the ratio of C mineralization to net N mineralization. During winter, freeze-thaw events, snow depth, and soil freezing depth explained little of the variation in net nitrification and N mineralization rates among treatments. During two years of treatments, warming and altered precipitation rarely influenced the rates of N cycling, and there was no evidence of a seasonal pattern in the responses. In contrast, warming and drought dramatically decreased the apparent Q10 of net N mineralization and net nitrification, and the warming-induced decrease in apparent Q10 was more pronounced in ambient and wet treatments than the drought treatment. The ratio of C mineralization to net N mineralization varied over time and was sensitive to the interactive effects of warming and altered precipitation. Although many studies have found that warming tends to accelerate N cycling, our results suggest that warming can have little to no effect on N cycling in some ecosystems. Thus, ecosystem models that assume that warming will consistently increase N mineralization rates and inputs of plant-available N may overestimate the increase in terrestrial productivity and the magnitude of an important

Finnish Secondary School Students' Interreligious Sensitivity

ERIC Educational Resources Information Center

Holm, Kristiina; Nokelainen, Petri; Tirri, Kirsi

2014-01-01

The aim of this study was to assess the self-evaluations of Finnish secondary school students' (N?=?549) interreligious sensitivity. The data were collected from 12-16-year-old young people with a 15-item Interreligious Sensitivity Scale Questionnaire (IRRSSQ). The IRRSSQ is based on Abu-Nimer's Developmental Model of Interreligious Sensitivity,…

Factors associated with fathers' caregiving activities and sensitivity with young children. NICHD Early Child Care Research Network.

PubMed

2000-06-01

A multifactorial model was used to identify child, sociodemographic, paternal, and maternal characteristics associated with 2 aspects of fathers' parenting. Fathers were interviewed about their caregiving responsibilities at 6, 15, 24, and 36 months, and a subset was videotaped during father-child play at 6 and 36 months. Caregiving activities and sensitivity during play interactions were predicted by different factors. Fathers were more involved in caregiving when fathers worked fewer hours and mothers worked more hours, when fathers and mothers were younger, when fathers had more positive personalities, when mothers reported greater marital intimacy, and when children were boys. Fathers who had less traditional child-rearing beliefs, were older, and reported more marital intimacy were more sensitive during play. These findings are consistent with a multifactorial and multidimensional view of fathering.

Maximum Likelihood Dynamic Factor Modeling for Arbitrary "N" and "T" Using SEM

ERIC Educational Resources Information Center

Voelkle, Manuel C.; Oud, Johan H. L.; von Oertzen, Timo; Lindenberger, Ulman

2012-01-01

This article has 3 objectives that build on each other. First, we demonstrate how to obtain maximum likelihood estimates for dynamic factor models (the direct autoregressive factor score model) with arbitrary "T" and "N" by means of structural equation modeling (SEM) and compare the approach to existing methods. Second, we go beyond standard time…

Studying the protein organization of the postsynaptic density by a novel solid phase- and chemical cross-linking-based technology.

PubMed

Liu, Szu-Heng; Cheng, Huei-Hsuan; Huang, San-Yuan; Yiu, Pei-Chun; Chang, Yen-Chung

2006-06-01

Agarose beads carrying a cleavable, fluorescent, and photoreactive cross-linking reagent on the surface were synthesized and used to selectively pull out the proteins lining the surface of supramolecules. A quantitative comparison of the abundances of various proteins in the sample pulled out by the beads from supramolecules with their original abundances could provide information on the spatial arrangement of these proteins in the supramolecule. The usefulness of these synthetic beads was successfully verified by trials using a synthetic protein complex consisting of three layers of different proteins on glass coverslips. By using these beads, we determined the interior or superficial locations of five major and 19 minor constituent proteins in the postsynaptic density (PSD), a large protein complex and the landmark structure of asymmetric synapses in the mammalian central nervous system. The results indicate that alpha,beta-tubulins, dynein heavy chain, microtubule-associated protein 2, spectrin, neurofilament H and M subunits, an hsp70 protein, alpha-internexin, dynamin, and PSD-95 protein reside in the interior of the PSD. Dynein intermediate chain, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors, kainate receptors, N-cadherin, beta-catenin, N-ethylmaleimide-sensitive factor, an hsc70 protein, and actin reside on the surface of the PSD. The results further suggest that the N-methyl-d-aspartate receptors and the alpha-subunits of calcium/calmodulin-dependent protein kinase II are likely to reside on the surface of the PSD although with unique local protein organizations. Based on our results and the known interactions between various PSD proteins from data mining, a model for the molecular organization of the PSD is proposed.

Cutaneous sensitivity in unilateral trans-tibial amputees

PubMed Central

Templeton, Cale A.; Strzalkowski, Nicholas D. J.; Galvin, Patti

2018-01-01

Aim To examine tactile sensitivity in the leg and foot sole of below-knee amputees (diabetic n = 3, traumatic n = 1), and healthy control subjects (n = 4), and examine the association between sensation and balance. Method Vibration perception threshold (VPT; 3, 40, 250Hz) and monofilaments (MF) were used to examine vibration and light touch sensitivity on the intact limb, residual limb, and homologous locations on controls. A functional reach test was performed to assess functional balance. Results Tactile sensitivity was lower for diabetic amputee subjects compared to age matched controls for both VPT and MF; which was expected due to presence of diabetic peripheral neuropathy. In contrast, the traumatic amputee participant showed increased sensitivity for VPT at 40Hz and 250Hz vibration in both the intact and residual limbs compared to controls. Amputees with lower tactile sensitivity had shorter reach distances compared to those with higher sensitivity. Conclusion Changes in tactile sensitivity in the residual limb of trans-tibial amputees may have implications for the interaction between the amputee and the prosthetic device. The decreased skin sensitivity observed in the residual limb of subjects with diabetes is of concern as changes in skin sensitivity may be important in 1) identification/prevention of excessive pressure and 2) for functional stability. Interestingly, we saw increased residual limb skin sensitivity in the individual with the traumatic amputation. Although not measured directly in the present study, this increase in tactile sensitivity may be related to cortical reorganisation, which is known to occur following amputation, and would support similar findings observed in upper limb amputees. PMID:29856766

Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy.

PubMed

Kloster Smerud, H; Fellström, B; Hällgren, R; Osagie, S; Venge, P; Kristjánsson, G

2010-11-01

sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN). in this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analyzed for IgA and IgG antibodies to alpha-lactalbumin, beta-lactoglobulin, casein and soy. 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins. The levels of IgG antibodies to alpha-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar. No differences were seen in serum levels of IgA or IgG antibodies to soy. it is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients.

Spatiotemporal Risk of Bacillary Dysentery and Sensitivity to Meteorological Factors in Hunan Province, China.

PubMed

Xu, Chengdong; Xiao, Gexin; Wang, Jinfeng; Zhang, Xiangxue; Liang, Jinjun

2017-12-29

Bacillary dysentery remains a public health concern in the world. Hunan Province is one of the provinces having the highest risk of bacillary dysentery in China, however, the spatial-temporal distribution, variation of bacillary dysentery and sensitivity to meteorological factors in there are unclear. In this paper, a Bayesian space-time hierarchical model (BSTHM) was used to detect space-time variation, and effects of meteorological factors between 2010 and 2015. The risk of bacillary dysentery showed apparent spatial-temporal heterogeneity. The highest risk occurred in the summer season. Economically undeveloped mountainous areas in the west and south of the province had the highest incidence rates. Twenty three (18.9%) and 20 (16.4%) counties were identified as hot and cold spots, respectively. Among the hotspots, 11 counties (47.8%) exhibited a rapidly decreasing trend, suggesting they may become low-risk areas in the future. Of the cold spot counties, six (30%) showed a slowly decreasing trend, and may have a higher risk in the future. Among meteorological factors, air temperature, relative humidity, and wind speed all played a significant role in the spatial-temporal distribution of bacillary dysentery risk. These findings can contribute to the implementation of an early warning system for controlling and preventing bacillary dysentery.

Spatiotemporal Risk of Bacillary Dysentery and Sensitivity to Meteorological Factors in Hunan Province, China

PubMed Central

Xu, Chengdong; Xiao, Gexin; Wang, Jinfeng; Zhang, Xiangxue; Liang, Jinjun

2017-01-01

Bacillary dysentery remains a public health concern in the world. Hunan Province is one of the provinces having the highest risk of bacillary dysentery in China, however, the spatial-temporal distribution, variation of bacillary dysentery and sensitivity to meteorological factors in there are unclear. In this paper, a Bayesian space-time hierarchical model (BSTHM) was used to detect space-time variation, and effects of meteorological factors between 2010 and 2015. The risk of bacillary dysentery showed apparent spatial-temporal heterogeneity. The highest risk occurred in the summer season. Economically undeveloped mountainous areas in the west and south of the province had the highest incidence rates. Twenty three (18.9%) and 20 (16.4%) counties were identified as hot and cold spots, respectively. Among the hotspots, 11 counties (47.8%) exhibited a rapidly decreasing trend, suggesting they may become low-risk areas in the future. Of the cold spot counties, six (30%) showed a slowly decreasing trend, and may have a higher risk in the future. Among meteorological factors, air temperature, relative humidity, and wind speed all played a significant role in the spatial-temporal distribution of bacillary dysentery risk. These findings can contribute to the implementation of an early warning system for controlling and preventing bacillary dysentery. PMID:29286297

Anxiety sensitivity and working memory capacity: Risk factors and targets for health behavior promotion.

PubMed

Otto, Michael W; Eastman, Abraham; Lo, Stephen; Hearon, Bridget A; Bickel, Warren K; Zvolensky, Michael; Smits, Jasper A J; Doan, Stacey N

2016-11-01

Understanding the nature and influence of specific risk profiles is increasingly important for health behavior promotion. The purpose of this article is to document the value of two factors-anxiety sensitivity (AS) and working memory capacity (WMC)-for enhancing risk for the initiation and/or maintenance of a range of negative health behaviors. AS is a distress-related risk factor that potentiates avoidance/coping motivations for negative health behaviors. Stress provides the conditions for negative somatic and affective states, and AS amplifies the aversiveness of these experiences and correspondingly hinders adaptive functioning. In contrast, low WMC is hypothesized to exert its effect by decreasing the capacity to filter out current temptations, attenuating a focus on longer-term goals and impairing the application of relevant coping skills at times of stress. In this review, we provide conceptual models for the separate roles of high AS and low WMC in negative health behaviors, review the influence of these factors on specific health behavior exemplars (eating behaviors/obesity, physical activity, smoking, alcohol use, and sleep promotion), provide preliminary evidence for their value as independent treatment targets for health-behavior promotion, and encourage specific research directions in relation to these variables. Copyright © 2016. Published by Elsevier Ltd.

Sensitivity of the ViroSeq HIV-1 Genotyping System for Detection of the K103N Resistance Mutation in HIV-1 Subtypes A, C, and D

PubMed Central

Church, Jessica D.; Jones, Dana; Flys, Tamara; Hoover, Donald; Marlowe, Natalia; Chen, Shu; Shi, Chanjuan; Eshleman, James R.; Guay, Laura A.; Jackson, J. Brooks; Kumwenda, Newton; Taha, Taha E.; Eshleman, Susan H.

2006-01-01

The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants. PMID:16931582

Diagnostic values of vascular endothelial growth factor and epidermal growth factor receptor for benign and malignant hydrothorax.

PubMed

Gu, Yan; Zhang, Min; Li, Guo-Hua; Gao, Jun-Zhen; Guo, Liping; Qiao, Xiao-Juan; Wang, Li-Hong; He, Lan; Wang, Mei-Ling; Yan, Li; Fu, Xiu-Hua

2015-02-05

Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this study was to analyze the correlation between levels of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in patients with benign and malignant hydrothorax. The contents of VEGF in the pleural effusion and serum of the patients with malignant pleural effusion (n = 35) and benign pleural effusion (n = 30) were detected by double antibody sandwich enzyme linked immunosorbent assay. The gene copy number level of EGFR in pleural effusion was detected by fluorescence in situ hybridization (FISH). The points with the highest sensitivity and specificity were selected as the critical values to calculate the diagnostic value of the VEGF in pleural effusion and serum, and EGFR gene copy number in pleural effusion. The contents of VEGF in pleural effusion and serum of patients with malignant hydrothorax were (384.91 ± 120.18), and (129.62 ± 46.35) ng/L, respectively, which were significantly higher than those of the patients with benign hydrothorax (207.97 ± 64.04), (63.49 ± 24.58) ng/L (P < 0.01). The sensitivity and specificity of detecting VEGF in pleural effusion were 80.0% and 96.7% (the boundary value was 297.06 ng/L), respectively for diagnosing benign and malignant hydrothorax. The sensitivity and specificity of serum were 74.3% and 96.7%, respectively (the boundary value was 99.21 ng/L) for diagnosing benign and malignant hydrothorax. The diagnostic efficiencies of EGFR and VEGF in hydrothorax were similar. There was a significant correlation between EGFR and VEGF in hydrothorax (P < 0.01). VEGF and EGFR play important roles in the formation of pleural effusion. VEGF differed significantly in benign and malignant pleural effusions, which contributed to differential diagnosis results of benign and malignant pleural effusions. It

Fundamental Factors Impacting the Stability of Phosphonate-Derivatized Ruthenium Polypyridyl Sensitizers Adsorbed on Metal Oxide Surfaces.

PubMed

Raber, McKenzie; Brady, Matthew David; Troian-Gautier, Ludovic; Dickenson, John; Marquard, Seth L; Hyde, Jacob; Lopez, Santiago; Meyer, Gerald J; Meyer, Thomas J; Harrison, Daniel P

2018-06-08

A series of 18 ruthenium(II) polypyridyl complexes were synthesized and evaluated under electrochemically oxidative conditions, which generates the Ru(III) oxidation state and mimics the harsh conditions experienced during the kinetically-limited regime that can occur in dye-sensitized solar cells (DSSCs) and dye-sensitized photoelectrosynthesis cells (DSPECs), to further develop fundamental insights into the factors governing molecular sensitizer surface stability in aqueous 0.1 M HClO4 (aq). Both desorption and oxidatively induced ligand substitution were observed on planar fluorine doped tin oxide, FTO, electrodes, with a dependence on the E1/2 Ru(III/II) redox potential dictating the comparative ratios of the processes. Complexes such as RuP4OMe (E1/2 = 0.91 vs Ag/AgCl) displayed virtually only desorption, while complexes such as RuPbpz (E1/2 > 1.62 V vs Ag/AgCl) displayed only chemical decomposition. Comparing isomers of 4,4'- and 5,5-disubstituted-2,2'-bipyridine ancillary polypyridyl ligands, a dramatic increase in the rate of desorption of the Ru(III) complexes was observed for the 5,5'-ligands. Nanoscopic indium doped tin oxide thin films, nanoITO, were also sensitized and analyzed with cyclic voltammetry, UV-Vis absorption spectroscopy, and XPS, allowing for further distinction of desorption versus ligand substitution processes. Desorption loss to bulk solution associated with the planar surface of FTO is essentially non-existent on nanoITO, where both desorption and ligand substitution are shut down with RuP4OMe. These results revealed that minimizing time spent in the oxidized form, incorporating electron donating groups, maximizing hydrophobicity, and minimizing molecular bulk near the adsorbed ligand are critical to optimizing the performance of ruthenium(II) polypyridyl complexes in dye-sensitized solar cell devices.

Estimation of regional differences in wind erosion sensitivity in Hungary

NASA Astrophysics Data System (ADS)

Mezősi, G.; Blanka, V.; Bata, T.; Kovács, F.; Meyer, B.

2015-01-01

In Hungary, wind erosion is one of the most serious natural hazards. Spatial and temporal variation in the factors that determine the location and intensity of wind erosion damage are not well known, nor are the regional and local sensitivities to erosion. Because of methodological challenges, no multi-factor, regional wind erosion sensitivity map is available for Hungary. The aim of this study was to develop a method to estimate the regional differences in wind erosion sensitivity and exposure in Hungary. Wind erosion sensitivity was modelled using the key factors of soil sensitivity, vegetation cover and wind erodibility as proxies. These factors were first estimated separately by factor sensitivity maps and later combined by fuzzy logic into a regional-scale wind erosion sensitivity map. Large areas were evaluated by using publicly available data sets of remotely sensed vegetation information, soil maps and meteorological data on wind speed. The resulting estimates were verified by field studies and examining the economic losses from wind erosion as compensated by the state insurance company. The spatial resolution of the resulting sensitivity map is suitable for regional applications, as identifying sensitive areas is the foundation for diverse land development control measures and implementing management activities.

Energetics, kinetics, and pathway of SNARE folding and assembly revealed by optical tweezers.

PubMed

Zhang, Yongli

2017-07-01

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion. A long-standing hypothesis suggests that SNAREs act like a zipper to draw the two membranes into proximity and thereby force them to fuse. However, a quantitative test of this SNARE zippering hypothesis was hindered by difficulties to determine the energetics and kinetics of SNARE assembly and to identify the relevant folding intermediates. Here, we first review different approaches that have been applied to study SNARE assembly and then focus on high-resolution optical tweezers. We summarize the folding energies, kinetics, and pathways of both wild-type and mutant SNARE complexes derived from this new approach. These results show that synaptic SNAREs assemble in four distinct stages with different functions: slow N-terminal domain association initiates SNARE assembly; a middle domain suspends and controls SNARE assembly; and rapid sequential zippering of the C-terminal domain and the linker domain directly drive membrane fusion. In addition, the kinetics and pathway of the stagewise assembly are shared by other SNARE complexes. These measurements prove the SNARE zippering hypothesis and suggest new mechanisms for SNARE assembly regulated by other proteins. © 2017 The Protein Society.

Efficient dye-sensitized solar cells from mesoporous zinc oxide nanostructures sensitized by N719 dye

NASA Astrophysics Data System (ADS)

Kumara, G. R. A.; Deshapriya, U.; Ranasinghe, C. S. K.; Jayaweera, E. N.; Rajapakse, R. M. G.

2018-03-01

Dye-sensitized solar cells (DSCs) have attracted a great deal of attention due to their low-cost and high power conversion efficiencies. They usually utilize an interconnected nanoparticle layer of TiO2 as the electron transport medium. From the fundamental point of view, faster mobility of electrons in ZnO is expected to contribute to better performance in DSCs than TiO2, though the actual practical situation is quite the opposite. In this research, we addressed this problem by first applying a dense layer of ZnO on FTO followed by a mesoporous layer of interconnected ZnO nanoparticle layer, both were prepared by spray pyrolysis technique. The best cell shows a power conversion efficiency of 5.2% when the mesoporous layer thickness is 14 μm and the concentration of the N719 dye in dye coating solution is 0.3 mM, while a cell without a dense layer shows 4.2% under identical conditions. The surface concentration of dye adsorbed in the cell with a dense layer and that without a dense layer are 5.00 × 10‑7 and 3.34 × 10‑7 mol/cm2, respectively. The cell with the dense layer has an electron lifetime of 54.81 ms whereas that without the dense layer is 11.08 ms. As such, the presence of the dense layer improves DSC characteristics of ZnO-based DSCs.

Maternal sensitivity: a concept analysis.

PubMed

Shin, Hyunjeong; Park, Young-Joo; Ryu, Hosihn; Seomun, Gyeong-Ae

2008-11-01

The aim of this paper is to report a concept analysis of maternal sensitivity. Maternal sensitivity is a broad concept encompassing a variety of interrelated affective and behavioural caregiving attributes. It is used interchangeably with the terms maternal responsiveness or maternal competency, with no consistency of use. There is a need to clarify the concept of maternal sensitivity for research and practice. A search was performed on the CINAHL and Ovid MEDLINE databases using 'maternal sensitivity', 'maternal responsiveness' and 'sensitive mothering' as key words. The searches yielded 54 records for the years 1981-2007. Rodgers' method of evolutionary concept analysis was used to analyse the material. Four critical attributes of maternal sensitivity were identified: (a) dynamic process involving maternal abilities; (b) reciprocal give-and-take with the infant; (c) contingency on the infant's behaviour and (d) quality of maternal behaviours. Maternal identity and infant's needs and cues are antecedents for these attributes. The consequences are infant's comfort, mother-infant attachment and infant development. In addition, three positive affecting factors (social support, maternal-foetal attachment and high self-esteem) and three negative affecting factors (maternal depression, maternal stress and maternal anxiety) were identified. A clear understanding of the concept of maternal sensitivity could be useful for developing ways to enhance maternal sensitivity and to maximize the developmental potential of infants. Knowledge of the attributes of maternal sensitivity identified in this concept analysis may be helpful for constructing measuring items or dimensions.

Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells

PubMed Central

Chen, Chuangui; Ma, Zhao; Zhang, Hongdian; Liu, Xiaoqiong; Yu, Zhentao

2017-01-01

Background The aim of this study was to elucidate the role of Krüppel-Like factor 4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells, which may eventually help to improve the treatment efficacy. Material/Methods Human esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1, EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their sensitivity to cisplatin. 5-Azacytidine-2′-deoxycytidine (5′-Aza-CdR) treatment and methylation-specific PCR (MS-PCR) were used to detect the methylation status for KLF4. Cell viability, apoptosis, and cell cycle were measured using methyl thiazolyl tetrazolium (MTT) assay, Annexin V affinity assay, and flow cytometry, respectively. Results The sensitivity to cisplatin was different in the seven ESCC cell lines, with TE-1 having the lowest sensitivity and KYSE140 having the highest sensitivity. Interestingly, the level of KLF4 was relatively low in TE-1 cells; while it was high in KYSE140 cells. These results suggested that KLF4 may be involved in cisplatin resistance. The promoter region was mostly unmethylated in KYSE140 cells; while it was hypermethylated in TE-1 cells. After treatment with demethylation reagent 5-Aza-CdR, cisplatin sensitivities were significantly increased after upregulation of KLF4, as the IC50 values were significantly decreased in the TE-1 cell treated with 5-Aza-CdR. Furthermore, upregulation of KLF4 induced cell apoptosis and cell cycle arrest at S phase. Conclusions KLF4 enhances the sensitivity of cisplatin to ESCC cells through apoptosis induction and cell cycle arrest. Our data provided a novel insight to the mechanism of cisplatin resistance; overexpression of KLF4 may be a potential therapeutic strategy for cisplatin resistance in human ESCC. PMID:28694421

Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells.

PubMed

Chen, Chuangui; Ma, Zhao; Zhang, Hongdian; Liu, Xiaoqiong; Yu, Zhentao

2017-07-11

BACKGROUND The aim of this study was to elucidate the role of Krüppel-Like factor 4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells, which may eventually help to improve the treatment efficacy. MATERIAL AND METHODS Human esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1, EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their sensitivity to cisplatin. 5-Azacytidine-2'-deoxycytidine (5'-Aza-CdR) treatment and methylation-specific PCR (MS-PCR) were used to detect the methylation status for KLF4. Cell viability, apoptosis, and cell cycle were measured using methyl thiazolyl tetrazolium (MTT) assay, Annexin V affinity assay, and flow cytometry, respectively. RESULTS The sensitivity to cisplatin was different in the seven ESCC cell lines, with TE-1 having the lowest sensitivity and KYSE140 having the highest sensitivity. Interestingly, the level of KLF4 was relatively low in TE-1 cells; while it was high in KYSE140 cells. These results suggested that KLF4 may be involved in cisplatin resistance. The promoter region was mostly unmethylated in KYSE140 cells; while it was hypermethylated in TE-1 cells. After treatment with demethylation reagent 5-Aza-CdR, cisplatin sensitivities were significantly increased after upregulation of KLF4, as the IC50 values were significantly decreased in the TE-1 cell treated with 5-Aza-CdR. Furthermore, upregulation of KLF4 induced cell apoptosis and cell cycle arrest at S phase. CONCLUSIONS KLF4 enhances the sensitivity of cisplatin to ESCC cells through apoptosis induction and cell cycle arrest. Our data provided a novel insight to the mechanism of cisplatin resistance; overexpression of KLF4 may be a potential therapeutic strategy for cisplatin resistance in human ESCC.

Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats

PubMed Central

Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L.; He, Yongcheng; Wang, Niansong; Liang, Mingyu

2016-01-01

Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13BN26 rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13BN26 rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7–8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

Probing the N = 14 subshell closure: g factor of the 26Mg (21+) state

NASA Astrophysics Data System (ADS)

McCormick, B. P.; Stuchbery, A. E.; Kibédi, T.; Lane, G. J.; Reed, M. W.; Eriksen, T. K.; Hota, S. S.; Lee, B. Q.; Palalani, N.

2018-04-01

The first-excited state g factor of 26Mg has been measured relative to the g factor of the 24Mg (21+) state using the high-velocity transient-field technique, giving g = + 0.86 ± 0.10. This new measurement is in strong disagreement with the currently adopted value, but in agreement with the sd-shell model using the USDB interaction. The newly measured g factor, along with E (21+) and B (E 2) systematics, signal the closure of the νd5/2 subshell at N = 14. The possibility that precise g-factor measurements may indicate the onset of neutron pf admixtures in first-excited state even-even magnesium isotopes below 32Mg is discussed and the importance of precise excited-state g-factor measurements on sd shell nuclei with N ≠ Z to test shell-model wavefunctions is noted.

Revisiting traditional risk factors for rejection and graft loss after kidney transplantation.

PubMed

Dunn, T B; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O G; Pruett, T L; Bray, R A; Gebel, H M; Matas, A J

2011-10-01

Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Sleep System Sensitization: Evidence for Changing Roles of Etiological Factors in Insomnia

PubMed Central

Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Anderson, Jason R.; Drake, Christopher L.

2016-01-01

Objectives To test for sensitization of the sleep system in response to insomnia development and major life stress. In addition, to evaluate the impact on depression and anxiety associated with sleep system sensitization. Methods A longitudinal study with three annual assessments. The community-based sample included 262 adults with no history of insomnia or depression who developed insomnia 1 year after baseline (67.6% female; 44.0±13.4y). Measures included the Ford Insomnia Response to Stress Test to assess sleep reactivity, Quick Inventory of Depressive Symptomatology, and Beck Anxiety Inventory. Insomnia classification was based on DSM-IV criteria. Sleep system sensitization was operationally defined as significant increases in sleep reactivity. Results Sensitization of the sleep system was observed from baseline to insomnia onset at 1-y follow-up among insomniacs with low premorbid vulnerability (p<.001), resulting in 68.3% of these individuals re-classified as highly sleep reactive. Major life stress was associated with greater sleep system sensitization (p=.02). Results showed that sleep reactivity at 2-y follow-up remained elevated among those with low premorbid vulnerability, even after insomnia remission (p<.01). Finally, analyses revealed that increases in sleep reactivity predicted greater depression (p<.001) and anxiety (p<.001) at insomnia onset. The impact of sensitization on depression was stable at 2-y follow-up (p=.01). Conclusions Evidence supports sensitization of the sleep system as consequence of insomnia development and major life stress among individuals with low premorbid sleep reactivity. Sleep system sensitization may serve as a mechanism by which insomnia is perpetuated. Harmful effects of the sensitization process may increase risk for insomnia-related depression and anxiety. PMID:27448474

Attachment Insecurity Predicts Punishment Sensitivity in Anorexia Nervosa.

PubMed

Keating, Charlotte; Castle, David J; Newton, Richard; Huang, Chia; Rossell, Susan L

2016-10-01

Individuals with anorexia nervosa (AN) experience insecure attachment. We investigated whether insecure attachment is associated with punishment and reward sensitivity in women with AN. Women with AN (n = 24) and comparison women (n = 26) (CW) completed The Eating Disorder Examination Questionnaire, Depression Anxiety Stress Scale, The Attachment Style Questionnaire, and Sensitivity to Punishment/Sensitivity to Reward Questionnaire. Participants with AN returned higher ratings for insecure attachment (anxious and avoidant) experiences and greater sensitivity to punishment (p = 0.001) than CW. In AN, sensitivity to punishment was positively correlated with anxious attachment and negative emotionality but not eating disorder symptoms. Regression analysis revealed that anxious attachment independently predicted punishment sensitivity in AN. Anxious attachment experiences are related to punishment sensitivity in AN, independent of negative emotionality and eating disorder symptoms. Results support ongoing investigation of the contribution of attachment experiences in treatment and recovery.

Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer.

PubMed

Garcia-Alonso, Luz; Iorio, Francesco; Matchan, Angela; Fonseca, Nuno; Jaaks, Patricia; Peat, Gareth; Pignatelli, Miguel; Falcone, Fiammetta; Benes, Cyril H; Dunham, Ian; Bignell, Graham; McDade, Simon S; Garnett, Mathew J; Saez-Rodriguez, Julio

2018-02-01

Transcriptional dysregulation induced by aberrant transcription factors (TF) is a key feature of cancer, but its global influence on drug sensitivity has not been examined. Here, we infer the transcriptional activity of 127 TFs through analysis of RNA-seq gene expression data newly generated for 448 cancer cell lines, combined with publicly available datasets to survey a total of 1,056 cancer cell lines and 9,250 primary tumors. Predicted TF activities are supported by their agreement with independent shRNA essentiality profiles and homozygous gene deletions, and recapitulate mutant-specific mechanisms of transcriptional dysregulation in cancer. By analyzing cell line responses to 265 compounds, we uncovered numerous TFs whose activity interacts with anticancer drugs. Importantly, combining existing pharmacogenomic markers with TF activities often improves the stratification of cell lines in response to drug treatment. Our results, which can be queried freely at dorothea.opentargets.io, offer a broad foundation for discovering opportunities to refine personalized cancer therapies. Significance: Systematic analysis of transcriptional dysregulation in cancer cell lines and patient tumor specimens offers a publicly searchable foundation to discover new opportunities to refine personalized cancer therapies. Cancer Res; 78(3); 769-80. ©2017 AACR . ©2017 American Association for Cancer Research.

The Negative Affect Hypothesis of Noise Sensitivity

PubMed Central

Shepherd, Daniel; Heinonen-Guzejev, Marja; Heikkilä, Kauko; Dirks, Kim N.; Hautus, Michael J.; Welch, David; McBride, David

2015-01-01

Some studies indicate that noise sensitivity is explained by negative affect, a dispositional tendency to negatively evaluate situations and the self. Individuals high in such traits may report a greater sensitivity to other sensory stimuli, such as smell, bright light and pain. However, research investigating the relationship between noise sensitivity and sensitivity to stimuli associated with other sensory modalities has not always supported the notion of a common underlying trait, such as negative affect, driving them. Additionally, other explanations of noise sensitivity based on cognitive processes have existed in the clinical literature for over 50 years. Here, we report on secondary analyses of pre-existing laboratory (n = 74) and epidemiological (n = 1005) data focusing on the relationship between noise sensitivity to and annoyance with a variety of olfactory-related stimuli. In the first study a correlational design examined the relationships between noise sensitivity, noise annoyance, and perceptual ratings of 16 odors. The second study sought differences between mean noise and air pollution annoyance scores across noise sensitivity categories. Results from both analyses failed to support the notion that, by itself, negative affectivity explains sensitivity to noise. PMID:25993104

High Sensitivity Detection of CdSe/ZnS Quantum Dot-Labeled DNA Based on N-type Porous Silicon Microcavities.

PubMed

Lv, Changwu; Jia, Zhenhong; Lv, Jie; Zhang, Hongyan; Li, Yanyu

2017-01-01

N-type macroporous silicon microcavity structures were prepared using electrochemical etching in an HF solution in the absence of light and oxidants. The CdSe/ZnS water-soluble quantum dot-labeled DNA target molecules were detected by monitoring the microcavity reflectance spectrum, which was characterized by the reflectance spectrum defect state position shift resulting from changes to the structures' refractive index. Quantum dots with a high refractive index and DNA coupling can improve the detection sensitivity by amplifying the optical response signals of the target DNA. The experimental results show that DNA combined with a quantum dot can improve the sensitivity of DNA detection by more than five times.

Newly emerging mutations in the matrix genes of the human influenza A(H1N1)pdm09 and A(H3N2) viruses reduce the detection sensitivity of real-time reverse transcription-PCR.

PubMed

Yang, Ji-Rong; Kuo, Chuan-Yi; Huang, Hsiang-Yi; Wu, Fu-Ting; Huang, Yi-Lung; Cheng, Chieh-Yu; Su, Yu-Ting; Chang, Feng-Yee; Wu, Ho-Sheng; Liu, Ming-Tsan

2014-01-01

New variants of the influenza A(H1N1)pdm09 and A(H3N2) viruses were detected in Taiwan between 2012 and 2013. Some of these variants were not detected in clinical specimens using a common real-time reverse transcription-PCR (RT-PCR) assay that targeted the conserved regions of the viral matrix (M) genes. An analysis of the M gene sequences of the new variants revealed that several newly emerging mutations were located in the regions where the primers or probes of the real-time RT-PCR assay bind; these included three mutations (G225A, T228C, and G238A) in the A(H1N1)pdm09 virus, as well as one mutation (C163T) in the A(H3N2) virus. These accumulated mismatch mutations, together with the previously identified C154T mutation of the A(H1N1)pdm09 virus and the C153T and G189T mutations of the A(H3N2) virus, result in a reduced detection sensitivity for the real-time RT-PCR assay. To overcome the loss of assay sensitivity due to mismatch mutations, we established a real-time RT-PCR assay using degenerate nucleotide bases in both the primers and probe and successfully increased the sensitivity of the assay to detect circulating variants of the human influenza A viruses. Our observations highlight the importance of the simultaneous use of different gene-targeting real-time RT-PCR assays for the clinical diagnosis of influenza.

An enzyme free electrochemical biosensor for sensitive detection of miRNA with a high discrimination factor by coupling the strand displacement reaction and catalytic hairpin assembly recycling.

PubMed

Yao, Juan; Zhang, Zhang; Deng, Zhenghua; Wang, Youqiang; Guo, Yongcan

2017-10-23

An isothermal, enzyme free, ultra-specific and ultra-sensitive protocol for electrochemical detection of miRNAs is proposed based on the toehold-mediated strand displacement reaction (SDR) and non-enzymatic catalytic hairpin reaction (CHA) recycling. The SDR was first triggered only in the presence of target miRNA and this process also affects other miRNA interferences having similar target sequences, thus guaranteeing a high discrimination factor and could be used in rare content miRNA detection with various amounts of interferences having similar target sequences. The output protector strand then triggered enzyme free CHA amplification and generates plenty of hairpin self-assembly products. This process in turn influences SDR equilibrium to move to the right and generates large amounts of protector output to ensure analysis sensitivity. Compared with traditional CHA, our proposed method greatly improved the signal to noise ratio and shows excellent performance in rare miRNA detection with miRNA analogue interference. Under the optimal experimental conditions and using square wave voltammetry, the established biosensor could detect target miRNA-21 down to 30 fM (S/N = 3) with a dynamic range from 100 fM to 2 nM, and discriminate rare target miRNA-21 from mismatched miRNA with high selectivity. This method holds great promise in miRNA detection from human cancer cell lines and would be a versatile and powerful tool for clinical molecular diagnostics.

Sleep system sensitization: evidence for changing roles of etiological factors in insomnia.

PubMed

Kalmbach, David A; Pillai, Vivek; Arnedt, J Todd; Anderson, Jason R; Drake, Christopher L

2016-05-01

To test for sensitization of the sleep system in response to insomnia development and major life stress. In addition, to evaluate the impact on depression and anxiety associated with sleep system sensitization. A longitudinal study with three annual assessments. The community-based sample included 262 adults with no history of insomnia or depression who developed insomnia one year after baseline (67.6% female; 44.0 ± 13.4 yr). Measures included the Ford Insomnia Response to Stress Test to assess sleep reactivity, Quick Inventory of Depressive Symptomatology, and Beck Anxiety Inventory. Insomnia classification was based on DSM-IV criteria. Sleep system sensitization was operationally defined as significant increases in sleep reactivity. Sensitization of the sleep system was observed from baseline to insomnia onset at 1-yr follow-up among insomniacs with low premorbid vulnerability (p < 0.001), resulting in 68.3% of these individuals re-classified as highly sleep reactive. Major life stress was associated with greater sleep system sensitization (p = 0.02). Results showed that sleep reactivity at 2-yr follow-up remained elevated among those with low premorbid vulnerability, even after insomnia remission (p < 0.01). Finally, analyses revealed that increases in sleep reactivity predicted greater depression (p < 0.001) and anxiety (p < 0.001) at insomnia onset. The impact of sensitization on depression was stable at 2-yr follow-up (p = 0.01). Evidence supports sensitization of the sleep system as a consequence of insomnia development and major life stress among individuals with low premorbid sleep reactivity. Sleep system sensitization may serve as a mechanism by which insomnia is perpetuated. Harmful effects of the sensitization process may increase risk for insomnia-related depression and anxiety. Copyright © 2016 Elsevier B.V. All rights reserved.

Computing sensitivity and selectivity in parallel factor analysis and related multiway techniques: the need for further developments in net analyte signal theory.

PubMed

Olivieri, Alejandro C

2005-08-01

Sensitivity and selectivity are important figures of merit in multiway analysis, regularly employed for comparison of the analytical performance of methods and for experimental design and planning. They are especially interesting in the second-order advantage scenario, where the latter property allows for the analysis of samples with a complex background, permitting analyte determination even in the presence of unsuspected interferences. Since no general theory exists for estimating the multiway sensitivity, Monte Carlo numerical calculations have been developed for estimating variance inflation factors, as a convenient way of assessing both sensitivity and selectivity parameters for the popular parallel factor (PARAFAC) analysis and also for related multiway techniques. When the second-order advantage is achieved, the existing expressions derived from net analyte signal theory are only able to adequately cover cases where a single analyte is calibrated using second-order instrumental data. However, they fail for certain multianalyte cases, or when third-order data are employed, calling for an extension of net analyte theory. The results have strong implications in the planning of multiway analytical experiments.

S-factor of 14 N (α, γ)18 F reaction at low-energies

NASA Astrophysics Data System (ADS)

Khalili, H.

2018-06-01

The astrophysical S-factor of the 14 N (α, γ)18 F reaction has been studied at range of bombarding energy 1-1.30 MeV. The 14 N (α, γ)18 F process is important in low energy astrophysics so that a possible source of energy in massive stars which have spent their hydrogen cycle. Using the Wood-saxon potential model, we have been calculated non resonances the astrophysical S-factors for the E 2 transition and our results for Eα = 0.0 MeV is S ≈ 0.5 MeV.b where from experimental is measured to Eα = 0.0 is S ≈ o . 7 MeV.b (Couch et al., 1971) that in comparison with our data good agreement is achieved for the astrophysical S-factor of this process.

Interaction of early infant feeding, heredity and other environmental factors as determinants in the development of allergy and sensitization.

PubMed

Savilahti, Erkki

2008-01-01

The role of early infant nutrition in the development of allergic symptoms and allergic sensitization has been disputed for 70 years. Interaction between genetic factors and infant feeding has been limited to studies on parental heredity of allergy and length of breastfeeding, as well as the qualities of breast milk. In the 10 original studies comparing the development of allergic symptoms among children in whom breastfeeding duration was used as a risk factor separately among those with either positive or negative parental heredity for atopy, no definite answer could be found. The effect of early feeding was even changed in both heredity negative and positive groups when looking at symptoms at ages 2 and 5 years. Of 9 possible combinations, 6 were present in the studies, and none in more than 2 studies. For sensitization, long breastfeeding was a risk in 3 of 5 reports if the family history of allergy was positive, and in 2 if negative. Low levels of soluble CD14 and cow's milk-specific IgA antibodies in breast milk may increase an infant's risk of developing allergy.

Rotation sensitivity analysis of a two-dimensional array of coupled resonators

NASA Astrophysics Data System (ADS)

Zamani Aghaie, Kiarash; Vigneron, Pierre-Baptiste; Digonnet, Michel J. F.

2015-03-01

In this paper, we study the rotation sensitivity of a gyroscope made of a two-dimensional array of coupled resonators consisting of N columns of one-dimensional coupled resonant optical waveguides (CROWs) connected by two bus waveguides, each CROW consisting of M identical ring resonators. We show that the maximum rotation sensitivity of this structure is a strong function of the parity of the number of rows M. For an odd number of rows, and when the number of columns is small, the maximum sensitivity is high, and it is slightly lower than the maximum sensitivity of a single-ring resonator with two input/output waveguides (the case M = N = 1), which is a resonant waveguide optical gyroscope (RWOG). For an even M and small N, the maximum sensitivity is much lower than that of the RWOG. Increasing the number columns N increases the sensitivity of an even-row 2D CROW sublinearly, as N0.39, up to 30 columns. In comparison, the maximum sensitivity of an RWOG of equal area increases faster, as √N. The sensitivity of the 2D CROW therefore always lags behind that of the RWOG. For a 2×2 CROW, if the spacing between the columns L is increased sufficiently the maximum sensitivity increases linearly with L due to the presence of a composite Mach- Zehnder interferometer in the structure. However, for equal footprints this sensitivity is also not larger than that of a single-ring resonator. Regardless of the number of rows and columns and the spacing, for the same footprint and propagation loss, a 2D CROW gyroscope is not more sensitive than an RWOG.

Sex-sensitive cognitive performance in untreated patients with early onset gender identity disorder.

PubMed

Haraldsen, I R; Opjordsmoen, S; Egeland, T; Finset, A

2003-10-01

We explored whether the cognitive performance of gender identity disorder patients (GID) was comparable to that of their biological sex or skewed towards that of their gender identity. We tested four potentially sex-sensitive cognitive factors (rotation, visualization, perception, and verbalization) as well as two neutral factors (logic and arithmetic) in GID patients from Norway (GID-N, n = 33) or the USA (GID-US, n = 19) and in a control group (C, n = 29). The testing was undertaken prior to cross sex hormone treatment. Four-way ANOVA was applied in the final analysis of the cognitive performance and its dependency on different predictors (age, biological sex, education, group). In both GID groups as well as in the control group (C) males excelled in visualization and rotation, also when controlling for potential confounders (biological sex, group, age and education). No female advantage was detected. Furthermore, no interaction between biological sex and group assignment was revealed in the samples. In this study the cognitive pattern of GID patients is consistent with that of their biological sex and not that of their gender identity.

PtNi Alloy Cocatalyst Modification of Eosin Y-Sensitized g-C3N4/GO Hybrid for Efficient Visible-Light Photocatalytic Hydrogen Evolution

NASA Astrophysics Data System (ADS)

Wang, Peng; Zong, Lanlan; Guan, Zhongjie; Li, Qiuye; Yang, Jianjun

2018-02-01

An economic and effective Pt-based alloy cocatalyst has attracted considerable attention due to their excellent catalytic activity and reducing Pt usage. In this study, PtNi alloy cocatalyst was successfully decorated on the g-C3N4/GO hybrid photocatalyst via a facile chemical reduction method. The Eosin Y-sensitized g-C3N4/PtNi/GO-0.5% composite photocatalyst yields about 1.54 and 1178 times higher hydrogen evolution rate than the Eosin Y-sensitized g-C3N4/Pt/GO-0.5% and g-C3N4/Ni/GO-0.5% samples, respectively. Mechanism of enhanced performance for the g-C3N4/PtNi/GO composite was also investigated by different characterization, such as photoluminescence, transient photocurrent response, and TEM. These results indicated that enhanced charge separation efficiency and more reactive sites are responsible for the improved hydrogen evolution performance due to the positive synergetic effect between Pt and Ni. This study suggests that PtNi alloy can be used as an economic and effective cocatalyst for hydrogen evolution reaction. [Figure not available: see fulltext.

Toward an Empirical Multidimensional Structure of Anhedonia, Reward Sensitivity, and Positive Emotionality: An Exploratory Factor Analytic Study.

PubMed

Olino, Thomas M; McMakin, Dana L; Forbes, Erika E

2016-11-20

Positive emotionality, anhedonia, and reward sensitivity share motivational and experiential elements of approach motivation and pleasure. Earlier work has examined the interrelationships among these constructs from measures of extraversion. More recently, the Research Domain Criteria introduced the Positive Valence Systems as a primary dimension to better understand psychopathology. However, the suggested measures tapping this construct have not yet been integrated within the structural framework of personality, even at the level of self-report. Thus, this study conducted exploratory factor and exploratory bifactor analyses on 17 different dimensions relevant to approach motivation, spanning anhedonia, behavioral activation system functioning, and positive emotionality. Convergent validity of these dimensions is tested by examining associations with depressive symptoms. Relying on multiple indices of fit, our preferred model included a general factor along with specific factors of affiliation, positive emotion, assertiveness, and pleasure seeking. These factors demonstrated different patterns of association with depressive symptoms. We discuss the plausibility of this model and highlight important future directions for work on the structure of a broad Positive Valence Systems construct. © The Author(s) 2016.

Colour vision and light sensitivity in tunnel workers previously exposed to acrylamide and N-methylolacrylamide containing grouting agents.

PubMed

Goffeng, Lars Ole; Kjuus, Helge; Heier, Mona Skard; Alvestrand, Monica; Ulvestad, Bente; Skaug, Vidar

2008-01-01

The aim of the study was to examine possible persisting visual system effects in tunnel workers previously exposed to acrylamide and N-methylolacrylamide during grouting work. Visual field light sensitivity threshold and colour vision has been examined among 44 tunnel workers 2-10 years after exposure to acrylamide and N-methylolacrylamide containing grouting agents. Forty-four tunnel workers not involved in grouting operations served as control group. Information on exposure and background variables was obtained for all participants from a questionnaire. Visual light sensitivity threshold was measured using Humphrey Visual Field Static Perimeter 740, program 30-2 Fastpack, with red stimuli on white background, and colour vision, using Lanthony D-15 Desaturated Color test. Based on D-15d test results, colour confusion index (CCI), and a severity index (C-index) was calculated. The exposed group had a significantly higher threshold for detecting single stimuli in all parts of the inner 30 degrees of the visual field compared to the control group. The foveal threshold group difference was 1.4 dB (p=0.002) (mean value, both eyes). On the Lanthony 15 Hue Desaturated test, the exposed subjects made more errors in sorting blue colours, and a statistically significant increase in C-index was observed. Surrogate measures for duration and intensity of exposure gave no further improvement of the model. The results indicate slightly reduced light sensitivity and reduced colour discrimination among the exposed subjects compared to the controls. The findings may be due to previous exposure to acrylamide containing grouts among the tunnel workers.

Deep pain sensitivity is correlated with oral-health-related quality of life but not with prosthetic factors in complete denture wearers

PubMed Central

COSTA, Yuri Martins; PORPORATTI, André Luís; HILGENBERG-SYDNEY, Priscila Brenner; BONJARDIM, Leonardo Rigoldi; CONTI, Paulo César Rodrigues

2015-01-01

ABSTRACT Low pressure Pain Threshold (PPT) is considered a risk factor for Temporomandibular Disorders (TMD) and is influenced by psychological variables. Objectives To correlate deep pain sensitivity of masticatory muscles with prosthetic factors and Oral-Health-Related Quality of Life (OHRQoL) in completely edentulous subjects. Material and Methods A total of 29 complete denture wearers were recruited. The variables were: a) Pressure Pain Threshold (PPT) of the masseter and temporalis; b) retention, stability, and tooth wear of dentures; c) Vertical Dimension of Occlusion (VDO); d) Oral Health Impact Profile (OHIP) adapted to orofacial pain. The Kolmogorov-Smirnov test, the Pearson Product-Moment correlation coefficient, the Spearman Rank correlation coefficient, the Point-Biserial correlation coefficient, and the Bonferroni correction (α=1%) were applied to the data. Results The mean age (standard deviation) of the participants was of 70.1 years (9.5) and 82% of them were females. There were no significant correlations with prosthetic factors, but significant negative correlations were found between the OHIP and the PPT of the anterior temporalis (r=-0.50, 95% CI-0.73 to 0.17, p=0.005). Discussion The deep pain sensitivity of masticatory muscles in complete dentures wearers is associated with OHRQoL, but not with prosthetic factors. PMID:26814457

Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells

PubMed Central

Faião-Flores, F; Alves-Fernandes, D K; Pennacchi, P C; Sandri, S; Vicente, A L S A; Scapulatempo-Neto, C; Vazquez, V L; Reis, R M; Chauhan, J; Goding, C R; Smalley, K S; Maria-Engler, S S

2017-01-01

BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naïve cells. We also observed these findings in clinical melanoma specimens. Moreover, the increased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was instead correlated with the noncanonical Hh pathway, involving TGFβ/SMAD (transforming growth factor-β/Sma- and Mad-related family) signaling. Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with both growth arrest and senescence. Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of the melanoma cells in a three-dimensional skin reconstruct model and was associated with a decrease in metalloproteinase (MMP2/MMP9) expression and microphthalmia transcription factor upregulation. Gant61 monotherapy did not alter the drug sensitivity of naïve cells, but could reverse the resistance of melanoma cells chronically treated with vemurafenib. We further noted that alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, suggesting that this could be a potential therapeutic strategy for the prevention of therapeutic escape. Our results suggest that targeting the Hh pathway in BRAFi-resistant melanoma may represent a viable therapeutic strategy to restore vemurafenib

Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells.

PubMed

Faião-Flores, F; Alves-Fernandes, D K; Pennacchi, P C; Sandri, S; Vicente, A L S A; Scapulatempo-Neto, C; Vazquez, V L; Reis, R M; Chauhan, J; Goding, C R; Smalley, K S; Maria-Engler, S S

2017-03-30

BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naïve cells. We also observed these findings in clinical melanoma specimens. Moreover, the increased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was instead correlated with the noncanonical Hh pathway, involving TGFβ/SMAD (transforming growth factor-β/Sma- and Mad-related family) signaling. Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with both growth arrest and senescence. Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of the melanoma cells in a three-dimensional skin reconstruct model and was associated with a decrease in metalloproteinase (MMP2/MMP9) expression and microphthalmia transcription factor upregulation. Gant61 monotherapy did not alter the drug sensitivity of naïve cells, but could reverse the resistance of melanoma cells chronically treated with vemurafenib. We further noted that alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, suggesting that this could be a potential therapeutic strategy for the prevention of therapeutic escape. Our results suggest that targeting the Hh pathway in BRAFi-resistant melanoma may represent a viable therapeutic strategy to restore vemurafenib

Sensitivity of charge transport measurements to local inhomogeneities

NASA Astrophysics Data System (ADS)

Koon, Daniel; Wang, Fei; Hjorth Petersen, Dirch; Hansen, Ole

2012-02-01

We derive analytic expressions for the sensitivity of resistive and Hall measurements to local variations in a specimen's material properties in the combined linear limit of both small magnetic fields and small perturbations, presenting exact, algebraic expressions both for four-point probe measurements on an infinite plane and for symmetric, circular van der Pauw discs. We then generalize the results to obtain corrections to the sensitivities both for finite magnetic fields and for finite perturbations. Calculated functions match published results and computer simulations, and provide an intuitive, visual explanation for experimental misassignment of carrier type in n-type ZnO and agree with published experimental results for holes in a uniform material. These results simplify calculation and plotting of the sensitivities on an NxN grid from a problem of order N^5 to one of order N^3 in the arbitrary case and of order N^2 in the handful of cases that can be solved exactly, putting a powerful tool for inhomogeneity analysis in the hands of the researcher: calculation of the sensitivities requires little more than the solution of Laplace's equation on the specimen geometry.

Improved sensitivity by post-column chemical environment modification of CE-ESI-MS using a flow-through microvial interface.

PubMed

Risley, Jessica May; Chen, David Da Yong

2017-06-01

Post-column chemical environment modification can affect detection sensitivity and signal appearance when capillary electrophoresis is coupled through electrospray ionization to mass spectrometry (CE-ESI-MS). In this study, changes in the signal intensity and peak shape of N-Acetylneuraminic acid (Neu5Ac) were examined when the modifier solution used in a flow-through microvial interface for CE-ESI-MS was prepared using an acidic or basic background electrolyte (BGE) composition. The use of a basic modifier resulted in improved detection compared to the results obtained when an acidic modifier was used in negative ion mode. Increased sensitivity and more symmetrical peak shape were obtained. Using an acidic modifier, the LOD of Neu5Ac was 47.7 nM, whereas for a basic modifier, the LOD of Neu5Ac was 5.20 nM. The calculated asymmetry factor at 100 nM of Neu5Ac ranged from 0.71 to 1.5 when an acidic modifier was used, while the factor ranged from 1.0 to 1.1 when a basic modifier was used. Properly chosen post-column chemical modification can have a significant effect on the performance of the CE-MS system. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Key factors limiting the open circuit voltage of n(+)pp(+) indium phosphide solar cells