Sample records for dominant negative forms
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Chen, Xiqun; Rzhetskaya, Margarita; Kareva, Tatyana; Bland, Ross; During, Matthew J.; Tank, A. William; Kholodilov, Nikolai; Burke, Robert E.
2009-01-01
There is extensive evidence that the mitogen-activated protein kinase (MAPK) signaling cascade mediates programmed cell death in neurons. However, current evidence that the mixed linage kinases (MLKs), upstream in this cascade, mediate cell death is based, in the in vivo context, entirely on pharmacological approaches. The compounds used in these studies have neither complete specificity nor selectivity among these kinases. Therefore, to better address the molecular specificity of the MLKs in mediating neuron death, we used dominant-negative constructs delivered by AAV (adenoassociated virus) vector transfer. We assessed effects in a neurotoxin model of parkinsonism, in which neuroprotection by pharmacologic MLK inhibition has been reported. We find that two dominant-negative forms of dual leucine zipper kinase (DLK) inhibit apoptosis and enhance long-term survival of dopamine neurons, but a dominant negative of MLK3 does not. Interestingly, the kinase-dead form of DLK not only blocks apoptosis but also has trophic effects on dopamine neurons. Although the MAPK cascade activates a number of downstream cell death mediators, we find that inhibition of DLK correlates closely with blockade of phosphorylation of c-jun and prevention of cell death. We conclude that DLK acts primarily through c-jun phosphorylation to mediate cell death in this model. PMID:18199767
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The zinc fingers of the Small Optic Lobes (SOL) calpain bind polyubiquitin.
Hastings, Margaret H; Qiu, Alvin; Zha, Congyao; Farah, Carole A; Mahdid, Yacine; Ferguson, Larissa; Sossin, Wayne S
2018-05-28
The Small Optic Lobes (SOL) calpain is a highly conserved member of the calpain family expressed in the nervous system. A dominant negative form of the SOL calpain inhibited consolidation of one form of synaptic plasticity, non-associative facilitation, in sensory-motor neuronal cultures in Aplysia, presumably by inhibiting cleavage of protein kinase Cs (PKCs) into constitutively active protein kinase Ms (PKMs) (Hu et al, 2017a). SOL calpains have a conserved set of 5-6 N-terminal zinc fingers. Bioinformatic analysis suggests that these zinc fingers could bind to ubiquitin. In this study, we show that both the Aplysia and mouse SOL calpain (also known as Calpain 15) zinc fingers bind ubiquitinated proteins, and we confirm that Aplysia SOL binds poly- but not mono or di-ubiquitin. No specific zinc finger is required for polyubiquitin binding. Neither polyubiquitin nor calcium was sufficient to induce purified Aplysia SOL calpain to autolyse or to cleave the atypical PKC to PKM in vitro. In Aplysia, overexpression of the atypical PKC in sensory neurons leads to an activity-dependent cleavage event and an increase in nuclear ubiquitin staining. Activity-dependent cleavage is partially blocked by a dominant negative SOL calpain, but not by a dominant negative classical calpain. The cleaved PKM was stabilized by the dominant negative classical calpain and destabilized by a dominant negative form of the PKM stabilizing proteinKIdney/BRAin protein(KIBRA). These studies provide new insight into SOL calpain's function and regulation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Williams, Melissa J; Tiedens, Larissa Z
2016-02-01
Previous research suggests that women, more than men, experience negative outcomes when they display dominance. A closer look, however, reveals ambiguity about the specific forms of dominance proscribed for women. Here, we suggest that negative reactions to women's dominance, a counter-stereotypical behavior, may require that the behavior be clearly encoded as counter-stereotypical-which is less likely when the behavior is expressed implicitly. This hypothesis was tested with a meta-analysis of studies on the evaluation of individuals behaving dominantly, including articles not directly investigating gender. Results revealed that dominance indeed hurts women's, relative to men's, likability (although the overall effect is small, d = -0.19, k = 63), as well as more downstream outcomes such as hireability (d = -0.58, k = 20). More important, however, dominance expressed explicitly (e.g., direct demands) affected women's likability (d = -0.28) whereas implicit forms of dominance (e.g., eye contact) did not (d = 0.03). Finally, the effect of dominance on men's and women's perceived competence did not differ (d = 0.02, k = 31), consistent with the idea that it is interpersonal (rather than instrumental) evaluations that obstruct women leaders. Implications for theory, and for the success of male and female leaders, are discussed. (c) 2016 APA, all rights reserved).
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Ferenci, T; Lee, K S
1989-01-01
Maltoporin trimers constitute maltodextrin-selective channels in the outer membrane of Escherichia coli. To study the organization of the maltodextrin-binding site within trimers, dominance studies were undertaken with maltoporin variants of altered binding affinity. It has been established that amino acid substitutions at three dispersed regions of the maltoporin sequence (at residues 8, 82, and 360) resulted specifically in maltodextrin-binding defects and loss of maltodextrin channel selectivity; a substitution at residue 118 increased both binding affinity and maltodextrin transport. Strains heterodiploid for lamB were constructed in which these substitutions were encoded by chromosomal and plasmid-borne genes, and the relative level of maltoporin expression from these genes was estimated. Binding assays with bacteria forming maltoporin heterotrimers were performed in order to test for complementation between binding-negative alleles, negative dominance of negative over wild-type alleles, and possible dominance of negatives over the high-affinity allele. Double mutants with mutations affecting residues 8 and 118, 82 and 118, and 118 and 360 were constructed in vitro, and the dominance properties of the mutations in cis were also tested. There was no complementation between negatives and no negative dominance in heterotrimers. The high-affinity mutation was dominant over negatives in trans but not in cis. The affinity of binding sites in heterotrimer populations was characteristic of the high-affinity allele present and uninfluenced by the negative allele. These results are consistent with the presence of three discrete binding sites in a maltoporin trimer and suggest that the selectivity filter for maltodextrins is not at the interface between the three subunits. PMID:2521623
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Arribas-González, Esther; de Juan-Sanz, Jaime; Aragón, Carmen; López-Corcuera, Beatriz
2015-01-01
Hyperekplexia or startle disease is a rare clinical syndrome characterized by an exaggerated startle in response to trivial tactile or acoustic stimuli. This neurological disorder can have serious consequences in neonates, provoking brain damage and/or sudden death due to apnea episodes and cardiorespiratory failure. Hyperekplexia is caused by defective inhibitory glycinergic neurotransmission. Mutations in the human SLC6A5 gene encoding the neuronal GlyT2 glycine transporter are responsible for the presynaptic form of the disease. GlyT2 mediates synaptic glycine recycling, which constitutes the main source of releasable transmitter at glycinergic synapses. Although the majority of GlyT2 mutations detected so far are recessive, a dominant negative mutant that affects GlyT2 trafficking does exist. In this study, we explore the properties and structural alterations of the S512R mutation in GlyT2. We analyze its dominant negative effect that retains wild-type GlyT2 in the endoplasmic reticulum (ER), preventing surface expression. We show that the presence of an arginine rather than serine 512 provoked transporter misfolding, enhanced association to the ER-chaperone calnexin, altered association with the coat-protein complex II component Sec24D, and thereby impeded ER exit. The S512R mutant formed oligomers with wild-type GlyT2 causing its retention in the ER. Overexpression of calnexin rescued wild-type GlyT2 from the dominant negative effect of the mutant, increasing the amount of transporter that reached the plasma membrane and dampening the interaction between the wild-type and mutant GlyT2. The ability of chemical chaperones to overcome the dominant negative effect of the disease mutation on the wild-type transporter was demonstrated in heterologous cells and primary neurons. PMID:25480793
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Williams, R M; Rimsky, S; Buc, H
1996-08-01
Twelve different dominant negative mutants of the Escherichia coli nucleoid-associated protein, H-NS, have been selected and characterized in vivo. The mutants are all severely defective in promoter repression activity in a strain lacking H-NS, and they all disrupt the repression normally exerted by H-NS at two of its target promoters. From the locations of the alterations in these mutants, which result in both large truncations and amino acid substitutions, we propose that H-NAS contains at least two distinct domains. The in vitro protein-protein cross-linking data presented in this report indicate that the proposed N-terminal domain of H-NS has a role in H-NS multimerization. StpA is a protein with known structural and functional homologies to H-NS. We have analyzed the extent of these homologies by constructing and studying StpA mutants predicted to be dominant negative. Our data indicate that the substitutions and deletions found in dominant negative H-NS have similar effects in the context of StpA. We conclude that the domain organizations and functions in StpA and H-NS are closely related. Furthermore, dominant negative H-NS can disrupt the activity of native StpA, and reciprocally, dominant negative StpA can disrupt the activity of native H-NS. We demonstrate that the N-terminal domain of H-NS can be chemically cross-linked to both full-length H-NS and StpA. We account for these observations by proposing that H-NS and StpA have the ability to form hybrid species.
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Faramarzi, M; Esmailzadeh, S; Mosavi, S
2005-10-01
To examine the effects of women's subjective definitions of wife abuse and of their general attitudes to acceptance of male dominance on the occurrence of domestic violence. A case-control survey was conducted in the public health center of Babol University of Medical Sciences from November 2002 to October 2003. The Abuse Assessment Screen Form was used to identify partner violence, and the Abuse Definition Form and Abuse Attitude Form were applied to measure how the women defined wife abuse and their attitudes to male dominance. Women with positive attitudes to male dominance had experienced more physical and emotional abuse than those with negative attitudes toward male dominance (p < 0.05). Although living in villages, low level of education, female unemployment, and low family income were important risk factors for domestic violence, the strongest predictor of physical abuse was a positive attitude to male dominance. A positive attitude of women to male dominance increases the acceptance and frequency of partner violence. This finding shows the need to raise the educational levels of women and raise their awareness of their rights. This could convert an attitude of male dominance to equality of men and women.
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ERIC Educational Resources Information Center
LópezLeiva, Carlos A.; Khisty, Lena Licón
2014-01-01
In this paper, we discuss the characteristics of microaggressions based on minority language(s) as a form of discriminatory practice against non-dominant students in the mathematics context. Microaggressions are subtle, brief, and commonplace verbal, behavioral, or visual negative slights or insults toward people of color. We extend the concept of…
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Watase, K; Sekiguchi, M; Matsui, T A; Tagawa, Y; Wada, K
1997-01-01
We reported that a 33-amino-acid deletion (from tyrosine-715 to glycine-747) in a putative extracellular loop of GluR3 produced a mutant that exhibited dominant negative effects upon the functional expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [Sekiguchi et al. (1994) J. Biol. Chem. 269, 14559-14565]. In this study, we searched for a key residue in the dominant negative effects to explore the mechanism and examined the role of the residue in the function of the AMPA receptor. We prepared 20 GluR3 mutants with amino acid substitutions within the 33-amino-acid-region, and dominant negative effects were tested electrophysiologically in Xenopus oocytes co-expressing the mutant and normal subunits. Among the mutants, only a GluR3 mutant in which an original cysteine (Cys)-722 was replaced by alanine exhibited a dominant negative effect comparable with that of the original mutant in which the entire 33-amino-acid segment is deleted. The co-expression of the Cys-722 mutant did not inhibit the translation of normal subunits in oocytes. The Cys-722 mutant formed a functional homomeric receptor with significantly higher affinity for glutamate or kainate than a homomeric GluR3 receptor. The Cys-722 mutation greatly enhanced the sensitivity of GluR3 for aniracetam, which alters kinetic properties of AMPA receptors. The kainate-induced currents in oocytes expressing the Cys-722 mutant alone showed strong inward rectification. These results suggest that the Cys-722 in GluR3 is important for dominant negative effects and plays a crucial role in the determination of pharmacological properties in AMPA receptor function. PMID:9065754
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Hans, M A; Müller, M; Meyer-Ficca, M; Bürkle, A; Küpper, J H
1999-11-25
Poly(ADP-ribose) polymerase (PARP4) catalyzes the formation of ADP-ribose polymers covalently attached to proteins by using NAD+ as substrate. PARP is strongly activated by DNA single- or double-strand breaks and is thought to be involved in cellular responses to DNA damage. We characterized a dominant negative PARP mutant, i.e. the DNA-binding domain of this enzyme, whose overexpression in cells leads to increased genetic instability following DNA damage. In order to study whether PARP activity is also implicated in the process of tumorigenesis, we generated stably transfected HeLa cell clones with constitutive overexpression of dominant negative PARP and investigated tumor formation of these clones in nude mice. We found that inhibition of PARP activity dramatically reduces tumor forming ability of HeLa cells. Moreover, we provide strong evidence that the observed reduction in tumor forming ability is due to increased tumor cell apoptosis in vivo. Viewed together, our data and those from other groups show that inhibition of PARP enzyme activity interferes with DNA base excision repair and leads to increased genetic instability and recombination but, on the other hand, can sensitize cells to apoptotic stimuli and by this mechanism may prevent tumor formation.
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Specific formation of negative ions from leucine and isoleucine molecules
NASA Astrophysics Data System (ADS)
Papp, Peter; Shchukin, Pavel; Matejčík, Štefan
2010-01-01
Dissociative electron attachment (DEA) to gas phase leucine (Leu) and isoleucine (Ile) molecules was studied using experimental and quantum-chemical methods. The relative partial cross sections for DEA have been measured using crossed electron/molecular beams technique. Supporting ab initio calculations of the structure, energies of neutral molecules, fragments, and negative ions have been carried out at G3MP2 and B3LYP levels in order to interpret the experimental data. Leu and Ile exhibit several common features. The negative ionic fragments from both molecules are formed in the electron energy range from 0 to approximately 14 eV via three resonances (1.2, 5.5, and 8 eV). The relative partial cross sections for DEA Leu and Ile are very similar. The dominant negative ions formed were closed shell negative ions (M-H)- (m/z=130) formed preferentially via low electron energy resonance of 1.23 eV. Additional negative ions with m/z=115, 114, 113, 112, 84, 82, 74, 45, 26, and 17 have been detected.
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Choosing Silence for Equality in and through Schooling
ERIC Educational Resources Information Center
Lees, Helen E.
2016-01-01
This article considers silences and equality as combined from a theoretical perspective. Equality in and through chosen, deliberate and regular silence experience is seen as an equaliser: if no one is speaking no one can dominate. The article uses a bifurcated concept of silence: weak, negative forms and strong, positive forms. Only the strong…
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Panickar, Kiran S; Nonner, Doris; White, Michael G; Barrett, John N
2008-09-01
Activation of cyclin dependent kinases (Cdks) contributes to neuronal death following ischemia. We used oxygen-glucose deprivation (OGD) in septal neuronal cultures to test for possible roles of cell cycle proteins in neuronal survival. Increased cdc2-immunoreactive neurons were observed at 24 h after the end of 5 h OGD. Green fluorescent protein (GFP) or GFP along with a wild type or dominant negative form of the retinoblastoma protein (Rb), or cyclin-dependent kinase5 (Cdk5), were overexpressed using plasmid constructs. Following OGD, when compared to controls, neurons expressing both GFP and dominant negative Rb, RbDeltaK11, showed significantly less damage using microscopy imaging. Overexpression of Rb-wt did not affect survival. Surprisingly, overexpression of Cdk5-wild type significantly protected neurons from process disintegration but Cdk5T33, a dominant negative Cdk5, gave little or no protection. Thus phosphorylation of the cell cycle regulator, Rb, contributes to death in OGD in septal neurons but Cdk5 can have a protective role.
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ERIC Educational Resources Information Center
Kelly, Peter
2006-01-01
This paper argues that a particular form of Selfhood has come to dominate the horizons of identity in the Western democracies at this time--I refer to this form of personhood as the entrepreneurial Self. The paper argues that the figure (population) of "Youth at-risk", in its negativity, illuminates the positivity that is the entrepreneurial Self.…
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Dominant-negative inhibitors of the Clostridium perfringens epsilon-toxin.
Pelish, Teal M; McClain, Mark S
2009-10-23
The Clostridium perfringens epsilon-toxin is responsible for a severe, often lethal intoxication. In this study, we characterized dominant-negative inhibitors of the epsilon-toxin. Site-specific mutations were introduced into the gene encoding epsilon-toxin, and recombinant proteins were expressed in Escherichia coli. Paired cysteine substitutions were introduced at locations predicted to form a disulfide bond. One cysteine in each mutant was introduced into the membrane insertion domain of the toxin; the second cysteine was introduced into the protein backbone. Mutant proteins with cysteine substitutions at amino acid positions I51/A114 and at V56/F118 lacked detectable cytotoxic activity in a MDCK cell assay. Cytotoxic activity could be reconstituted in both mutant proteins by incubation with dithiothreitol, indicating that the lack of cytotoxic activity was attributable to the formation of a disulfide bond. Fluorescent labeling of the cysteines also indicated that the introduced cysteines participated in a disulfide bond. When equimolar mixtures of wild-type epsilon-toxin and mutant proteins were added to MDCK cells, the I51C/A114C and V56C/F118C mutant proteins each inhibited the activity of wild-type epsilon-toxin. Further analysis of the inhibitory activity of the I51C/A114C and V56C/F118C mutant proteins indicated that these proteins inhibit the ability of the active toxin to form stable oligomeric complexes in the context of MDCK cells. These results provide further insight into the properties of dominant-negative inhibitors of oligomeric pore-forming toxins and provide the basis for developing new therapeutics for treating intoxication by epsilon-toxin.
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Iyer, Vidyashankara; Hu, Lei; Schanté, Carole E; Vance, David; Chadwick, Chrystal; Jain, Nishant Kumar; Brey, Robert N; Joshi, Sangeeta B; Volkin, David B; Andra, Kiran K; Bann, James G; Mantis, Nicholas J; Middaugh, C Russell
2013-11-01
Dominant Negative Inhibitor (DNI) is a translocation-deficient homolog of recombinant protective antigen of Bacillus anthracis that is a candidate for a next generation anthrax vaccine. This study demonstrates that the biophysical characteristics of the DNI protein stored in lyophilized form at 4°C for 8 y were similar to recombinant Protective Antigen (rPA). To provide information on the accelerated stability of DNI, samples in the lyophilized form were subjected to thermal stress (40°C and 70°C for up to 4 weeks) and thoroughly evaluated using various biophysical and chemical characterization techniques. Results demonstrate preserved structural stability of the DNI protein under extreme conditions, suggesting long-term stability can be achieved for a vaccine that employs DNI, as desired for a biodefense countermeasure. Furthermore, the biological activity of the stressed DNI bound to the adjuvant Alhydrogel (®) was evaluated in mice and it was found that the immunogenicity DNI was not affected by thermal stress.
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Structure of the Dominant Negative S17N Mutant of Ras
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nassar, N.; Singh, K; Garcia-Diaz, M
2010-01-01
The use of the dominant negative mutant of Ras has been crucial in elucidating the cellular signaling of Ras in response to the activation of various membrane-bound receptors. Although several point mutants of Ras exhibit a dominant negative effect, the asparagine to serine mutation at position 17 (S17N) remains the most popular and the most effective at inhibiting the activation of endogenous Ras. It is now widely accepted that the dominant negative effect is due to the ability of the mutant to sequester upstream activators and its inability to activate downstream effectors. Here, we present the crystal structure of RasS17Nmore » in the GDP-bound form. In the three molecules that populate the asymmetric unit, the Mg{sup 2+} ion that normally coordinates the {beta}-phosphate is absent because of steric hindrance from the Asn17 side chain. Instead, a Ca{sup 2+} ion is coordinating the {alpha}-phosphate. Also absent from one molecule is electron density for Phe28, a conserved residue that normally stabilizes the nucleotide's guanine base. Except for Phe28, the nucleotide makes conserved interactions with Ras. Combined, the inability of Phe28 to stabilize the guanine base and the absence of a Mg{sup 2+} ion to neutralize the negative charges on the phosphates explain the weaker affinity of GDP for Ras. Our data suggest that the absence of the Mg{sup 2+} should also dramatically affect GTP binding to Ras and the proper positioning of Thr35 necessary for the activation of switch 1 and the binding to downstream effectors, a prerequisite for the triggering of signaling pathways.« less
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Anderson, Eric; Siegel, Erika H; Bliss-Moreau, Eliza; Barrett, Lisa Feldman
2011-06-17
Gossip is a form of affective information about who is friend and who is foe. We show that gossip does not influence only how a face is evaluated--it affects whether a face is seen in the first place. In two experiments, neutral faces were paired with negative, positive, or neutral gossip and were then presented alone in a binocular rivalry paradigm (faces were presented to one eye, houses to the other). In both studies, faces previously paired with negative (but not positive or neutral) gossip dominated longer in visual consciousness. These findings demonstrate that gossip, as a potent form of social affective learning, can influence vision in a completely top-down manner, independent of the basic structural features of a face.
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Yuan, Ji-Min; He, Bai-Liang; Yang, Lu-Yun; Guo, Chang-Jun; Weng, Shao-Ping; Li, Shengwen Calvin; He, Jian-Guo
2015-01-01
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus, Iridoviridae family, causing a severe systemic disease with high mortality in mandarin fish (Siniperca chuatsi) in China and Southeast Asia. At present, the pathogenesis of ISKNV infection is still not fully understood. Based on a genome-wide bioinformatics analysis of ISKNV-encoded proteins, we found that ISKNV open reading frame 119L (ORF119L) is predicted to encode a three-ankyrin-repeat (3ANK)-domain-containing protein, which shows high similarity to the dominant negative form of integrin-linked kinase (ILK); i.e., viral ORF119L lacks the ILK kinase domain. Thus, we speculated that viral ORF119L might affect the host ILK complex. Here, we demonstrated that viral ORF119L directly interacts with particularly interesting Cys-His-rich protein (PINCH) and affects the host ILK-PINCH interaction in vitro in fathead minnow (FHM) cells. In vivo ORF119L overexpression in zebrafish (Danio rerio) embryos resulted in myocardial dysfunctions with disintegration of the sarcomeric Z disk. Importantly, ORF119L overexpression in zebrafish highly resembles the phenotype of endogenous ILK inhibition, either by overexpressing a dominant negative form of ILK or by injecting an ILK antisense morpholino oligonucleotide. Intriguingly, ISKNV-infected mandarin fish develop disorganized sarcomeric Z disks in cardiomyocytes. Furthermore, phosphorylation of AKT, a downstream effector of ILK, was remarkably decreased in ORF119L-overexpressing zebrafish embryos. With these results, we show that ISKNV ORF119L acts as a domain-negative inhibitor of the host ILK, providing a novel mechanism for the megalocytivirus pathogenesis. Our work is the first to show the role of a dominant negative inhibitor of the host ILK from ISKNV (an iridovirus). Mechanistically, the viral ORF119L directly binds to the host PINCH, attenuates the host PINCH-ILK interaction, and thus impairs ILK signaling. Intriguingly, ORF119L-overexpressing zebrafish embryos and ISKNV-infected mandarin fish develop similar disordered sarcomeric Z disks in cardiomyocytes. These findings provide a novel mechanism for megalocytivirus pathogenesis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Manson, Joseph H.; Gervais, Matthew M.; Fessler, Daniel M. T.; Kline, Michelle A.
2014-01-01
The determinants of conversational dominance are not well understood. We used videotaped triadic interactions among unacquainted same-sex American college students to test predictions drawn from the theoretical distinction between dominance and prestige as modes of human status competition. Specifically, we investigated the effects of physical formidability, facial attractiveness, social status, and self-reported subclinical psychopathy on quantitative (proportion of words produced), participatory (interruptions produced and sustained), and sequential (topic control) dominance. No measure of physical formidability or attractiveness was associated with any form of conversational dominance, suggesting that the characteristics of our study population or experimental frame may have moderated their role in dominance dynamics. Primary psychopathy was positively associated with quantitative dominance and (marginally) overall triad talkativeness, and negatively associated (in men) with affect word use, whereas secondary psychopathy was unrelated to conversational dominance. The two psychopathy factors had significant opposing effects on quantitative dominance in a multivariate model. These latter findings suggest that glibness in primary psychopathy may function to elicit exploitable information from others in a relationally mobile society. PMID:25426962
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Manson, Joseph H; Gervais, Matthew M; Fessler, Daniel M T; Kline, Michelle A
2014-01-01
The determinants of conversational dominance are not well understood. We used videotaped triadic interactions among unacquainted same-sex American college students to test predictions drawn from the theoretical distinction between dominance and prestige as modes of human status competition. Specifically, we investigated the effects of physical formidability, facial attractiveness, social status, and self-reported subclinical psychopathy on quantitative (proportion of words produced), participatory (interruptions produced and sustained), and sequential (topic control) dominance. No measure of physical formidability or attractiveness was associated with any form of conversational dominance, suggesting that the characteristics of our study population or experimental frame may have moderated their role in dominance dynamics. Primary psychopathy was positively associated with quantitative dominance and (marginally) overall triad talkativeness, and negatively associated (in men) with affect word use, whereas secondary psychopathy was unrelated to conversational dominance. The two psychopathy factors had significant opposing effects on quantitative dominance in a multivariate model. These latter findings suggest that glibness in primary psychopathy may function to elicit exploitable information from others in a relationally mobile society.
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Negative quantum capacitance induced by midgap states in single-layer graphene.
Wang, Lin; Wang, Yang; Chen, Xiaolong; Zhu, Wei; Zhu, Chao; Wu, Zefei; Han, Yu; Zhang, Mingwei; Li, Wei; He, Yuheng; Xiong, Wei; Law, Kam Tuen; Su, Dangsheng; Wang, Ning
2013-01-01
We demonstrate that single-layer graphene (SLG) decorated with a high density of Ag adatoms displays the unconventional phenomenon of negative quantum capacitance. The Ag adatoms act as resonant impurities and form nearly dispersionless resonant impurity bands near the charge neutrality point (CNP). Resonant impurities quench the kinetic energy and drive the electrons to the Coulomb energy dominated regime with negative compressibility. In the absence of a magnetic field, negative quantum capacitance is observed near the CNP. In the quantum Hall regime, negative quantum capacitance behavior at several Landau level positions is displayed, which is associated with the quenching of kinetic energy by the formation of Landau levels. The negative quantum capacitance effect near the CNP is further enhanced in the presence of Landau levels due to the magnetic-field-enhanced Coulomb interactions.
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Negative Quantum Capacitance Induced by Midgap States in Single-layer Graphene
Wang, Lin; Wang, Yang; Chen, Xiaolong; Zhu, Wei; Zhu, Chao; Wu, Zefei; Han, Yu; Zhang, Mingwei; Li, Wei; He, Yuheng; Xiong, Wei; Law, Kam Tuen; Su, Dangsheng; Wang, Ning
2013-01-01
We demonstrate that single-layer graphene (SLG) decorated with a high density of Ag adatoms displays the unconventional phenomenon of negative quantum capacitance. The Ag adatoms act as resonant impurities and form nearly dispersionless resonant impurity bands near the charge neutrality point (CNP). Resonant impurities quench the kinetic energy and drive the electrons to the Coulomb energy dominated regime with negative compressibility. In the absence of a magnetic field, negative quantum capacitance is observed near the CNP. In the quantum Hall regime, negative quantum capacitance behavior at several Landau level positions is displayed, which is associated with the quenching of kinetic energy by the formation of Landau levels. The negative quantum capacitance effect near the CNP is further enhanced in the presence of Landau levels due to the magnetic-field-enhanced Coulomb interactions. PMID:23784258
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Anderson, Eric; Siegel, Erika H.; Bliss-Moreau, Eliza; Barrett, Lisa Feldman
2011-01-01
Gossip is a form of affective information about who is friend and who is foe. We show that gossip does not impact only how a face is evaluated—it affects whether a face is seen in the first place. In two experiments, neutral faces were paired with negative, positive, or neutral gossip and were then presented alone in a binocular rivalry paradigm (faces were presented to one eye, houses to the other). In both studies, faces previously paired with negative (but not positive or neutral) gossip dominated longer in visual consciousness. These findings demonstrate that gossip, as a potent form of social affective learning, can influence vision in a completely top-down manner, independent of the basic structural features of a face. PMID:21596956
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Ota, Satoshi; Tonou-Fujimori, Noriko; Yamasu, Kyo
2009-01-01
The roles of the FGF family growth factors and their receptors (FGFRs) in zebrafish embryos were examined using variously modified versions of the four FGFR genes (fgfr1-4). Constitutively active forms of all of the examined FGFRs (ca-FGFRs) caused dorsalization, brain caudalization, and secondary axis formation, indicating that the main FGF signal transduction downstream of the receptor is highly similar among FGFRs. All of the membrane-bound type of dominant-negative FGFRs (mdn-FGFRs) derived from the four fgfr genes, which interfere with endogenous FGFRs, produced posterior truncation, as previously reported in both Xenopus and zebrafish. mdn-FGFR3c had the strongest effects on embryos, progressively disrupting the posterior structure as the dose increased. At the highest dose, only the forebrain was formed. At lower doses, mdn-FGFR3c mainly suppressed the paraxial mesoderm. The co-injection of mRNA for different mdn-FGFRs and FGFs resulted in diverse suppression spectra of the respective FGFRs against FGFs. Only mdn-FGFR3c severely suppressed all of the FGFs examined. We also examined the effects of the secretory type of dominant-negative FGFRs (sdn-FGFRs), which are released from cells and trap FGF ligands. Only sdn-FGFR3c resulted in the characteristic effect of selectively disrupting the isthmic development, as well as the tailbud. The co-injection of the mRNA for sdn-FGFRs and FGFs suggested that sdn-FGFR3c inhibits FGFs of the FGF8 subfamily, which is consistent with its specific effects on development. We discuss the implications of our findings obtained in the present study.
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Miyazaki, Satsuki; Taniguchi, Hidenori; Moritoh, Yusuke; Tashiro, Fumi; Yamamoto, Tsunehiko; Yamato, Eiji; Ikegami, Hiroshi; Ozato, Keiko; Miyazaki, Jun-ichi
2010-11-01
Retinoid X receptors (RXRs) are members of the nuclear hormone receptor superfamily and are thought to be key regulators in differentiation, cellular growth, and gene expression. Although several experiments using pancreatic β-cell lines have shown that the ligands of nuclear hormone receptors modulate insulin secretion, it is not clear whether RXRs have any role in insulin secretion. To elucidate the function of RXRs in pancreatic β-cells, we generated a double-transgenic mouse in which a dominant-negative form of RXRβ was inducibly expressed in pancreatic β-cells using the Tet-On system. We also established a pancreatic β-cell line from an insulinoma caused by the β-cell-specific expression of simian virus 40 T antigen in the above transgenic mouse. In the transgenic mouse, expression of the dominant-negative RXR enhanced the insulin secretion with high glucose stimulation. In the pancreatic β-cell line, the suppression of RXRs also enhanced glucose-stimulated insulin secretion at a high glucose concentration, while 9-cis-retinoic acid, an RXR agonist, repressed it. High-density oligonucleotide microarray analysis showed that expression of the dominant-negative RXR affected the expression levels of a number of genes, some of which have been implicated in the function and/or differentiation of β-cells. These results suggest that endogenous RXR negatively regulates the glucose-stimulated insulin secretion. Given these findings, we propose that the modulation of endogenous RXR in β-cells may be a new therapeutic approach for improving impaired insulin secretion in type 2 diabetes.
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NASA Astrophysics Data System (ADS)
LópezLeiva, Carlos A.; Khisty, Lena Licón
2014-06-01
In this paper, we discuss the characteristics of microaggressions based on minority language(s) as a form of discriminatory practice against non-dominant students in the mathematics context. Microaggressions are subtle, brief, and commonplace verbal, behavioral, or visual negative slights or insults toward people of color. We extend the concept of microaggression to include discrimination based on a minority language. We draw on our work with Latinas/os in the USA to demonstrate the occurrence of microaggressions in the teaching act. Revealing microaggressions based on language has the potential of creating more equitable learning environments for non-dominant students and can point to possible directions for future research and improvements in the preparation of teachers who serve non-dominant students who speak a language other than the school's official language.
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Nayak, Ramesh C.; Keshava, Shiva; Esmon, Charles T.; Pendurthi, Usha R.; Rao, L. Vijaya Mohan
2013-01-01
Recent studies have established that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR). FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand complex. Rab GTPases are known to play a crucial role in the endocytic and exocytic pathways of receptors or receptor/ligand complexes. The present study was undertaken to investigate the role of Rab GTPases in the intracellular trafficking of EPCR and FVIIa. CHO-EPCR cells and human umbilical vein endothelial cells (HUVEC) were transduced with recombinant adenoviral vectors to express wild-type, constitutively active, or dominant negative mutant of various Rab GTPases. Cells were exposed to FVIIa conjugated with AF488 fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescence confocal microscopy. In cells expressing wild-type or constitutively active Rab4A, internalized AF488-FVIIa accumulated in early/sorting endosomes and its entry into the recycling endosomal compartment (REC) was inhibited. Expression of constitutively active Rab5A induced large endosomal structures beneath the plasma membrane where EPCR and FVIIa accumulated. Dominant negative Rab5A inhibited the endocytosis of EPCR-FVIIa. Expression of constitutively active Rab11 resulted in retention of accumulated AF488-FVIIa in the REC, whereas expression of a dominant negative form of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and prevented entry of internalized FVIIa into the REC. Expression of dominant negative Rab11 also inhibited the transport of FVIIa across the endothelium. Overall our data show that Rab GTPases regulate the internalization and intracellular trafficking of EPCR-FVIIa. PMID:23555015
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Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant.
Vassbotn, F S; Andersson, M; Westermark, B; Heldin, C H; Ostman, A
1993-01-01
A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions. Images PMID:8321214
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Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant.
Vassbotn, F S; Andersson, M; Westermark, B; Heldin, C H; Ostman, A
1993-07-01
A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions.
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Sekimoto, Kanako; Takayama, Mitsuo
2013-05-01
Collision-induced dissociation (CID) experiments were performed on atmospheric ion adducts [M + R](-) formed between various types of organic compounds M and atmospheric negative ions R(-) [such as O2(-), HCO3(-), COO(-)(COOH), NO2(-), NO3(-), and NO3(-)(HNO3)] in negative-ion mode atmospheric pressure corona discharge ionization (APCDI) mass spectrometry. All of the [M + R](-) adducts were fragmented to form deprotonated analytes [M - H](-) and/or atmospheric ions R(-), whose intensities in the CID spectra were dependent on the proton affinities of the [M - H](-) and R(-) fragments. Precursor ions [M + R](-) for which R(-) have higher proton affinities than [M - H](-) formed [M - H](-) as the dominant product. Furthermore, the CID of the adducts with HCO3(-) and NO3(-)(HNO3) led to other product ions such as [M + HO](-) and NO3(-), respectively. The fragmentation behavior of [M + R](-) for each R(-) observed was independent of analyte type (e.g., whether the analyte was aliphatic or aromatic, or possessed certain functional groups).
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Zhang, Qiong; Berkey, Robert; Pan, Zhiyong; Wang, Wenming; Zhang, Yi; Ma, Xianfeng; King, Harlan; Xiao, Shunyuan
2015-01-01
Powdery mildew fungi form feeding structures called haustoria inside epidermal cells of host plants to extract photosynthates for their epiphytic growth and reproduction. The haustorium is encased by an interfacial membrane termed the extrahaustorial membrane (EHM). The atypical resistance protein RPW8.2 from Arabidopsis is specifically targeted to the EHM where RPW8.2 activates haustorium-targeted (thus broad-spectrum) resistance against powdery mildew fungi. EHM-specific localization of RPW8.2 suggests the existence of an EHM-oriented protein/membrane trafficking pathway during EHM biogenesis. However, the importance of this specific trafficking pathway for host defense has not been evaluated via a genetic approach without affecting other trafficking pathways. Here, we report that expression of EHM-oriented, nonfunctional RPW8.2 chimeric proteins exerts dominant negative effect over functional RPW8.2 and potentially over other EHM-localized defense proteins, thereby compromising both RPW8.2-mediated and basal resistance to powdery mildew. Thus, our results highlight the importance of the EHM-oriented protein/membrane trafficking pathway for host resistance against haustorium-forming pathogens such as powdery mildew fungi.
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Floating plant dominance as a stable state
Scheffer, Marten; Szabó, Sándor; Gragnani, Alessandra; van Nes, Egbert H.; Rinaldi, Sergio; Kautsky, Nils; Norberg, Jon; Roijackers, Rudi M. M.; Franken, Rob J. M.
2003-01-01
Invasion by mats of free-floating plants is among the most important threats to the functioning and biodiversity of freshwater ecosystems ranging from temperate ponds and ditches to tropical lakes. Dark, anoxic conditions under thick floating-plant cover leave little opportunity for animal or plant life, and they can have large negative impacts on fisheries and navigation in tropical lakes. Here, we demonstrate that floating-plant dominance can be a self-stabilizing ecosystem state, which may explain its notorious persistence in many situations. Our results, based on experiments, field data, and models, represent evidence for alternative domains of attraction in ecosystems. An implication of our findings is that nutrient enrichment reduces the resilience of freshwater systems against a shift to floating-plant dominance. On the other hand, our results also suggest that a single drastic harvest of floating plants can induce a permanent shift to an alternative state dominated by rooted, submerged growth forms. PMID:12634429
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Delgado-Baquerizo, Manuel; Maestre, Fernando T; Eldridge, David J; Bowker, Matthew A; Ochoa, Victoria; Gozalo, Beatriz; Berdugo, Miguel; Val, James; Singh, Brajesh K
2016-03-01
The increase in aridity predicted with climate change will have a negative impact on the multiple functions and services (multifunctionality) provided by dryland ecosystems worldwide. In these ecosystems, soil communities dominated by mosses, lichens and cyanobacteria (biocrusts) play a key role in supporting multifunctionality. However, whether biocrusts can buffer the negative impacts of aridity on important biogeochemical processes controlling carbon (C), nitrogen (N), and phosphorus (P) pools and fluxes remains largely unknown. Here, we conducted an empirical study, using samples from three continents (North America, Europe and Australia), to evaluate how the increase in aridity predicted by climate change will alter the capacity of biocrust-forming mosses to modulate multiple ecosystem processes related to C, N and P cycles. Compared with soil surfaces lacking biocrusts, biocrust-forming mosses enhanced multiple functions related to C, N and P cycling and storage in semiarid and arid, but not in humid and dry-subhumid, environments. Most importantly, we found that the relative positive effects of biocrust-forming mosses on multifunctionality compared with bare soil increased with increasing aridity. These results were mediated by plant cover and the positive effects exerted by biocrust-forming mosses on the abundance of soil bacteria and fungi. Our findings provide strong evidence that the maintenance of biocrusts is crucial to buffer negative effects of climate change on multifunctionality in global drylands. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
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Miyai, Caio A; Carretero Sanches, Fábio H; Costa, Tânia M; Colpo, Karine Delevati; Volpato, Gilson L; Barreto, Rodrigo E
2011-12-01
Eye darkening has been linked to social status in fish. The subordinate's eyes darken, while the eyes of the dominant fish become pale. Although this phenomenon has been described in salmonid fishes and in the African cichlid Nile tilapia Oreochromis niloticus, it is unclear whether eye darkening correlates with a reduction in aggressive behaviour. Thus, we evaluated the link between social status and eye darkening. We evaluated whether the eye colours of subordinate fish correlate with the frequency of received attacks in a neotropical fish, the pearl cichlid Geophagus brasiliensis. We paired pearl cichlids and quantified both the aggressive behaviour and the eye darkening of each fish. As has been described for Nile tilapia and Atlantic salmon, a clear-cut hierarchical relationship formed, where dominance and subordination were associated with pale and dark eye colours, respectively. Initially, eye colour darkening was positively correlated with the frequency of received attacks; however, a negative association occurred following eye darkening, in which the intensity of aggressive interactions decreased. Thus, fish that initially received a high number of attacks signalled subordination more rapidly and intensely (rapid and dramatic eye darkening), thereby inducing a negative social feedback mechanism that led to reduced aggression. Copyright © 2011 Elsevier GmbH. All rights reserved.
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The development and maintenance of drug addiction.
Wise, Roy A; Koob, George F
2014-01-01
What is the defining property of addiction? We dust off a several-decades-long debate about the relative importance of two forms of reinforcement—positive reinforcement, subjectively linked to drug-induced euphoria, and negative reinforcement, subjectively linked to the alleviation of pain—both of which figure importantly in addiction theory; each of these forms has dominated addiction theory in its time. We agree that addiction begins with the formation of habits through positive reinforcement and that drug-opposite physiological responses often establish the conditions for negative reinforcement to come into play at a time when tolerance, in the form of increasing reward thresholds, appears to develop into positive reinforcement. Wise’s work has tended to focus on positive-reinforcement mechanisms that are important for establishing drug-seeking habits and reinstating them quickly after periods of abstinence, whereas Koob’s work has tended to focus on the negative-reinforcement mechanisms that become most obvious in the late stages of sustained addiction. While we tend to agree with each other about the early and late stages of addiction, we hold different views as to (i) the point between early and late at which the diagnosis of ‘addiction’ should be invoked, (ii) the relative importance of positive and negative reinforcement leading up to this transition, and (iii) the degree to which the specifics of negative reinforcement can be generalized across the range of addictive agents.
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Diévart, Anne; Dalal, Monica; Tax, Frans E.; Lacey, Alexzandria D.; Huttly, Alison; Li, Jianming; Clark, Steven E.
2003-01-01
The CLAVATA1 (CLV1) receptor kinase controls stem cell number and differentiation at the Arabidopsis shoot and flower meristems. Other components of the CLV1 signaling pathway include the secreted putative ligand CLV3 and the receptor-like protein CLV2. We report evidence indicating that all intermediate and strong clv1 alleles are dominant negative and likely interfere with the activity of unknown receptor kinase(s) that have functional overlap with CLV1. clv1 dominant-negative alleles show major differences from dominant-negative alleles characterized to date in animal receptor kinase signaling systems, including the lack of a dominant-negative effect of kinase domain truncation and the ability of missense mutations in the extracellular domain to act in a dominant-negative manner. We analyzed chimeric receptor kinases by fusing CLV1 and BRASSINOSTEROID INSENSITIVE1 (BRI1) coding sequences and expressing these in clv1 null backgrounds. Constructs containing the CLV1 extracellular domain and the BRI1 kinase domain were strongly dominant negative in the regulation of meristem development. Furthermore, we show that CLV1 expressed within the pedicel can partially replace the function of the ERECTA receptor kinase. We propose the presence of multiple receptors that regulate meristem development in a functionally related manner whose interactions are driven by the extracellular domains and whose activation requires the kinase domain. PMID:12724544
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Tharp, Andra Teten; Schumacher, Julie A.; McLeish, Alison C.; Samper, Rita E.; Coffey, Scott F.
2013-01-01
The current study employs dominance analysis to assess the relative importance of three constructs—hostility, impulsiveness, and emotional dysregulation (difficulties managing one’s emotions when experiencing negative emotion or distress)—in explaining psychological, physical, and sexual intimate partner violence (IPV) perpetration by men seeking alcohol treatment. A sample of 121 predominantly White, heterosexual men (average age 33.28, range = 18 - 62) enrolled in residential substance abuse treatment completed measures of emotional dysregulation, hostility, and impulsiveness, which are three highly related constructs identified as risk factors for both substance use disorders and IPV. The constructs collectively accounted for 20-25% of the variance in each form of IPV. Because impulsiveness, hostility, and emotional dysregulation are highly correlated, dominance analysis was used to examine which factor most strongly predicted each form of IPV. Dominance analysis findings favored hostility as a predictor of physical IPV perpetration, and impulsiveness as a predictor of sexual and psychological IPV perpetration. Differential associations between the constructs and each form of IPV may be used to inform assessment and treatment planning of men who abuse alcohol. Better understanding, preventing, and treating male-to-female IPV will protect women from the far-reaching consequences of this violence. PMID:23990693
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NASA Astrophysics Data System (ADS)
Bhattacharya, Bhaskar Deb; Hwang, Jiang-Shiou; Sarkar, Santosh Kumar; Rakhsit, Dibyendu; Murugan, K.; Tseng, Li-Chun
2015-01-01
Spatial and temporal distribution of community structure and seasonal distribution of mesozooplankton (MZ; 20-200 μm) in the context of environmental parameters were studied in the coastal waters of Indian Sundarban wetland formed at the confluence of Hugli (Ganges) River estuary, India. The work has been aimed for better understanding of its ecological characteristics in terms of the most dominant mesozooplankton group in a tropical mesomacrotidal setting. Samples were collected from four sampling sites of different hydrodynamic set up using a ring trawl net (Hydro-Bios No. 438 700, mesh size 200 μm) equipped with a calibrated flowmeter and both water and plankton samples were analyzed by standard methods. Distribution of MZ showed bimodality with two peak periods, primary peak during April coinciding with maximum number of copepod species (974 ind. m- 3) and the secondary one during August. Copepod was the most dominant taxon where the calanoids formed bulk of the biomass representing 33 species of 7 genera, while cyclopoids formed the next dominant group comprising 4 species of 3 genera followed by 4 monogeneric harpacticoid species. Results of correlation matrix revealed that two copepod families Acartiidae and Pseudodiaptomidae maintain negative relationship with other six families indicating that they form a group by themselves. Results of multiple regression analysis reveal that salinity, chlorophyll-a and transparency are the potential hydrological factors in the distribution and existence of the dominant copepods and total chaetognaths. An overall high diversity index values (max. 3.21) was associated with high richness index (4.39) and high evenness index (0.96) at the site of the mouth of the estuary. In terms of feeding guild, the herbivore copepods were dominant followed by omnivores. Cluster analysis confirmed an overall dominance of the calanoid copepod Bestiolina similis as a solitary group for all the sites. The chaetognath Sagitta bedoti was perennial in distribution where the contribution of juvenile form (recognized as Stage I) was dominant. Among the other MZ, hydromedusae, ctenophore, sergestid and mysid were also encountered contributing insignificant part of the total density. A long-term decadal change in copepod community was pronounced which might be due to climate-induced environmental changes which also modulate the physicochemical characteristics of water.
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Pogmore, Alex-Rose; Seistrup, Kenneth H; Strahl, Henrik
2018-04-01
Rather than being homogenous diffusion-dominated structures, biological membranes can exhibit areas with distinct composition and characteristics, commonly termed as lipid domains. Arguably the most comprehensively studied examples in bacteria are domains formed by cardiolipin, which have been functionally linked to protein targeting, the cell division process and the mode of action of membrane-targeting antimicrobials. Cardiolipin domains were originally identified in the Gram-negative model organism Escherichia coli based on preferential staining by the fluorescent membrane dye nonylacridine orange (NAO), and later reported to also exist in other Gram-negative and -positive bacteria. Recently, the lipid-specificity of NAO has been questioned based on studies conducted in E. coli. This prompted us to reanalyse cardiolipin domains in the Gram-positive model organism Bacillus subtilis. Here we show that logarithmically growing B. subtilis does not form microscopically detectable cardiolipin-specific lipid domains, and that NAO is not a specific stain for cardiolipin in this organism.
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2006-07-01
the skeletal muscle-specific muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor, Activin...and rates of breast cancer initiation and progression. 15. SUBJECT TERMS Breast cancer, skeletal muscle, myostatin , MPA, DMBA, Activin receptor 16...including interleukins, Insulin-like Growth Factor (IGF) isoforms, IGF-binding proteins and myostatin . To determine the effect of skeletal muscle mass
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Shi, Wen; Riquelme, Manuel A; Gu, Sumin; Jiang, Jean X
2018-03-21
Elevated oxidized stress contributes to lens cataracts, and gap junctions play important roles in maintaining lens transparency. As well as forming gap junctions, connexin (Cx) proteins also form hemichannels. Here, we report a new mechanism whereby hemichannels mediate transport of reductant glutathione into lens fiber cells and protect cells against oxidative stress. We found that Cx50 (also known as GJA8) hemichannels opened in response to H 2 O 2 in lens fiber cells but that transport through the channels was inhibited by two dominant-negative mutants in Cx50, Cx50P88S, which inhibits transport through both gap junctions and hemichannels, and Cx50H156N, which only inhibits transport through hemichannels and not gap junctions. Treatment with H 2 O 2 increased the number of fiber cells undergoing apoptosis, and this increase was augmented with dominant-negative mutants that disrupted both hemichannels formed from Cx46 (also known as GJA3) and Cx50, while Cx50E48K, which only impairs gap junctions, did not have such an effect. Moreover, hemichannels mediate uptake of glutathione, and this uptake protected lens fiber cells against oxidative stress, while hemichannels with impaired transport had less protective benefit from glutathione. Taken together, these results show that oxidative stress activates connexin hemichannels in the lens fiber cells and that hemichannels likely protect lens cell against oxidative damage through transporting extracellular reductants. © 2018. Published by The Company of Biologists Ltd.
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Lihoradova, Olga; Kalveram, Birte; Indran, Sabarish V.; Lokugamage, Nandadeva; Juelich, Terry L.; Hill, Terence E.; Tseng, Chien-Te K.; Gong, Bin; Fukushi, Shuetsu; Morikawa, Shigeru; Freiberg, Alexander N.
2012-01-01
Rift Valley fever virus (RVFV), belonging to the genus Phlebovirus, family Bunyaviridae, is endemic to sub-Saharan Africa and causes a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. MP-12 is the only RVFV strain excluded from the select-agent rule and handled at a biosafety level 2 (BSL2) laboratory. MP-12 encodes a functional major virulence factor, the NSs protein, which contributes to its residual virulence in pregnant ewes. We found that 100% of mice subcutaneously vaccinated with recombinant MP-12 (rMP12)-murine PKRN167 (mPKRN167), which encodes a dominant-negative form of mouse double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in place of NSs, were protected from wild-type (wt) RVFV challenge, while 72% of mice vaccinated with MP-12 were protected after challenge. rMP12-mPKRN167 induced alpha interferon (IFN-α) in sera, accumulated RVFV antigens in dendritic cells at the local draining lymph nodes, and developed high levels of neutralizing antibodies, while parental MP-12 induced neither IFN-α nor viral-antigen accumulation at the draining lymph node yet induced a high level of neutralizing antibodies. The present study suggests that the expression of a dominant-negative PKR increases the immunogenicity and efficacy of live-attenuated RVFV vaccine, which will lead to rational design of safe and highly immunogenic RVFV vaccines for livestock and humans. PMID:22573861
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Zulianello, Laurence; Kaneko, Kiyotoshi; Scott, Michael; Erpel, Susanne; Han, Dong; Cohen, Fred E.; Prusiner, Stanley B.
2000-01-01
Polymorphic basic residues near the C terminus of the prion protein (PrP) in humans and sheep appear to protect against prion disease. In heterozygotes, inhibition of prion formation appears to be dominant negative and has been simulated in cultured cells persistently infected with scrapie prions. The results of nuclear magnetic resonance and mutagenesis studies indicate that specific substitutions at the C-terminal residues 167, 171, 214, and 218 of PrPC act as dominant-negative, inhibitors of PrPSc formation (K. Kaneko et al., Proc. Natl. Acad. Sci. USA 94:10069–10074, 1997). Trafficking of substituted PrPC to caveaola-like domains or rafts by the glycolipid anchor was required for the dominant-negative phenotype; interestingly, amino acid replacements at multiple sites were less effective than single-residue substitutions. To elucidate which domains of PrPC are responsible for dominant-negative inhibition of PrPSc formation, we analyzed whether N-terminally truncated PrP(Q218K) molecules exhibited dominant-negative effects in the conversion of full-length PrPC to PrPSc. We found that the C-terminal domain of PrP is not sufficient to impede the conversion of the full-length PrPC molecule and that N-terminally truncated molecules (with residues 23 to 88 and 23 to 120 deleted) have reduced dominant-negative activity. Whether the N-terminal region of PrP acts by stabilizing the C-terminal domain of the molecule or by modulating the binding of PrPC to an auxiliary molecule that participates in PrPSc formation remains to be established. PMID:10756050
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Nacke, Lennart E; Nacke, Anne; Lindley, Craig A
2009-10-01
In recent years, an aging demographic majority in the Western world has come to the attention of the game industry. The recently released "brain-training" games target this population, and research investigating gameplay experience of the elderly using this game form is lacking. This study employs a 2 x 2 mixed factorial design (age group: young and old x game form: paper and Nintendo DS) to investigate effects of age and game form on usability, self-assessment, and gameplay experience in a supervised field study. Effectiveness was evaluated in task completion time, efficiency as error rate, together with self-assessment measures (arousal, pleasure, dominance) and game experience (challenge, flow, competence, tension, positive and negative affect). Results indicate players, regardless of age, are more effective and efficient using pen-and-paper than using a Nintendo DS console. However, the game is more arousing and induces a heightened sense of flow in digital form for gamers of all ages. Logic problem-solving challenges within digital games may be associated with positive feelings for the elderly but with negative feelings for the young. Thus, digital logic-training games may provide positive gameplay experience for an aging Western civilization.
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A unified engineering model of the first stroke in downward negative lightning
NASA Astrophysics Data System (ADS)
Nag, Amitabh; Rakov, Vladimir A.
2016-03-01
Each stroke in a negative cloud-to-ground lightning flash is composed of downward leader and upward return stroke processes, which are usually modeled individually. The first stroke leader is stepped and starts with preliminary breakdown (PB) which is often viewed as a separate process. We present the first unified engineering model for computing the electric field produced by a sequence of PB, stepped leader, and return stroke processes, serving to transport negative charge to ground. We assume that a negatively charged channel extends downward in a stepped fashion during both the PB and leader stages. Each step involves a current wave that propagates upward along the newly formed channel section. Once the leader attaches to ground, an upward propagating return stroke neutralizes the charge deposited along the channel. Model-predicted electric fields are in reasonably good agreement with simultaneous measurements at both near (hundreds of meters, electrostatic field component is dominant) and far (tens of kilometers, radiation field component is dominant) distances from the lightning channel. Relations between the features of computed electric field waveforms and model input parameters are examined. It appears that peak currents associated with PB pulses are similar to return stroke peak currents, and the observed variation of electric radiation field peaks produced by leader steps at different heights above ground is influenced by the ground corona space charge.
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Yang, G-X; Sun, Y; Tsuneyama, K; Zhang, W; Leung, P S C; He, X-S; Ansari, A A; Bowlus, C; Ridgway, W M; Gershwin, M E
2016-08-01
During chronic inflammation, interleukin (IL)-22 expression is up-regulated in both CD4 and CD8 T cells, exerting a protective role in infections. However, in autoimmunity, IL-22 appears to have either a protective or a pathogenic role in a variety of murine models of autoimmunity and, by extrapolation, in humans. It is not clear whether IL-22 itself mediates inflammation or is a by-product of inflammation. We have taken advantage of the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice that develop both inflammatory bowel disease and autoimmune cholangitis and studied the role and the biological function of IL-22 by generating IL-22(-/-) dnTGF-βRII mice. Our data suggest that the influence of IL-22 on autoimmunity is determined in part by the local microenvironment. In particular, IL-22 deficiency exacerbates tissue injury in inflammatory bowel disease, but has no influence on either the hepatocytes or cholangiocytes in the same model. These data take on particular significance in the previously defined effects of IL-17A, IL-12p40 and IL-23p19 deficiency and emphasize that, in colitis, there is a dominant role of IL-23/T helper type 17 (Th17) signalling. Furthermore, the levels of IL-22 are IL-23-dependent. The use of cytokine therapy in patients with autoimmune disease has significant potential, but must take into account the overlapping and often promiscuous effects that can theoretically exacerbate inflammation. © 2016 British Society for Immunology.
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Coastal urbanisation affects microbial communities on a dominant marine holobiont.
Marzinelli, Ezequiel M; Qiu, Zhiguang; Dafforn, Katherine A; Johnston, Emma L; Steinberg, Peter D; Mayer-Pinto, Mariana
2018-01-01
Host-associated microbial communities play a fundamental role in the life of eukaryotic hosts. It is increasingly argued that hosts and their microbiota must be studied together as 'holobionts' to better understand the effects of environmental stressors on host functioning. Disruptions of host-microbiota interactions by environmental stressors can negatively affect host performance and survival. Substantial ecological impacts are likely when the affected hosts are habitat-forming species (e.g., trees, kelps) that underpin local biodiversity. In marine systems, coastal urbanisation via the addition of artificial structures is a major source of stress to habitat formers, but its effect on their associated microbial communities is unknown. We characterised kelp-associated microbial communities in two of the most common and abundant artificial structures in Sydney Harbour-pier-pilings and seawalls-and in neighbouring natural rocky reefs. The kelp Ecklonia radiata is the dominant habitat-forming species along 8000 km of the temperate Australian coast. Kelp-associated microbial communities on pilings differed significantly from those on seawalls and natural rocky reefs, possibly due to differences in abiotic (e.g., shade) and biotic (e.g., grazing) factors between habitats. Many bacteria that were more abundant on kelp on pilings belonged to taxa often associated with macroalgal diseases, including tissue bleaching in Ecklonia . There were, however, no differences in kelp photosynthetic capacity between habitats. The observed differences in microbial communities may have negative effects on the host by promoting fouling by macroorganisms or by causing and spreading disease over time. This study demonstrates that urbanisation can alter the microbiota of key habitat-forming species with potential ecological consequences.
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Hu, Liyan; Pandey, Amit V; Eggimann, Sandra; Rüfenacht, Véronique; Möslinger, Dorothea; Nuoffer, Jean-Marc; Häberle, Johannes
2013-11-29
Argininosuccinic aciduria (ASA) is an autosomal recessive urea cycle disorder caused by deficiency of argininosuccinate lyase (ASL) with a wide clinical spectrum from asymptomatic to severe hyperammonemic neonatal onset life-threatening courses. We investigated the role of ASL transcript variants in the clinical and biochemical variability of ASA. Recombinant proteins for ASL wild type, mutant p.E189G, and the frequently occurring transcript variants with exon 2 or 7 deletions were (co-)expressed in human embryonic kidney 293T cells. We found that exon 2-deleted ASL forms a stable truncated protein with no relevant activity but a dose-dependent dominant negative effect on enzymatic activity after co-expression with wild type or mutant ASL, whereas exon 7-deleted ASL is unstable but seems to have, nevertheless, a dominant negative effect on mutant ASL. These findings were supported by structural modeling predictions for ASL heterotetramer/homotetramer formation. Illustrating the physiological relevance, the predominant occurrence of exon 7-deleted ASL was found in two patients who were both heterozygous for the ASL mutant p.E189G. Our results suggest that ASL transcripts can contribute to the highly variable phenotype in ASA patients if expressed at high levels. Especially, the exon 2-deleted ASL variant may form a heterotetramer with wild type or mutant ASL, causing markedly reduced ASL activity.
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Blouin, Ashley M; Stern, Anna L; Han, Sungho; Theberge, Florence R; Wang, Chuansong; During, Matthew J; Baraban, Jay M; Reti, Irving M
2013-08-01
The medial prefrontal cortex (mPFC) plays a key role in extinction learning. Previously, we found that expression of a neuronal activity-regulated pentraxin (Narp) dominant-negative construct in the mPFC of mice blocked extinction of morphine-conditioned place preference. To further investigate the role of mPFC Narp in the extinction of drug seeking, we tested whether mPFC Narp is necessary for the extinction of heroin self-administration in rats. Specifically, we injected an adeno-associated viral vector expressing a dominant-negative form of Narp (NarpN) into the infralimbic region of the mPFC of rats and compared lever presses during extinction to those of rats injected with a control virus. In contrast to our previous study, we found that injection of NarpN did not affect extinction of heroin self-administration. Our findings suggest that mPFC Narp is necessary for extinction of opiate seeking in the Pavlovian-conditioned place preference paradigm but not in the operant paradigm of drug self-administration.
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Hepatic p38α regulates gluconeogenesis by suppressing AMPK.
Jing, Yanyan; Liu, Wei; Cao, Hongchao; Zhang, Duo; Yao, Xuan; Zhang, Shengjie; Xia, Hongfeng; Li, Dan; Wang, Yu-cheng; Yan, Jun; Hui, Lijian; Ying, Hao
2015-06-01
It is proposed that p38 is involved in gluconeogenesis, however, the genetic evidence is lacking and precise mechanisms remain poorly understood. We sought to delineate the role of hepatic p38α in gluconeogenesis during fasting by applying a loss-of-function genetic approach. We examined fasting glucose levels, performed pyruvate tolerance test, imaged G6Pase promoter activity, as well as determined the expression of gluconeogenic genes in mice with a targeted deletion of p38α in liver. Results were confirmed both in vivo and in vitro by using an adenoviral dominant-negative form of p38α (p38α-AF) and the constitutively active mitogen-activated protein kinase 6, respectively. Adenoviral dominant-negative form of AMP-activated protein kinase α (DN-AMPKα) was employed to test our proposed model. Mice lacking hepatic p38α exhibited reduced fasting glucose level and impaired gluconeogenesis. Interestingly, hepatic deficiency of p38α did not result in an alteration in CREB phosphorylation, but led to an increase in AMPKα phosphorylation. Adenoviral DN-AMPKα could abolish the effect of p38α-AF on gluconeogenesis. Knockdown of up-steam transforming growth factor β-activated kinase 1 decreased the AMPKα phosphorylation induced by p38α-AF, suggesting a negative feedback loop. Consistently, inverse correlations between p38 and AMPKα phosphorylation were observed during fasting and in diabetic mouse models. Importantly, adenoviral p38α-AF treatment ameliorated hyperglycemia in diabetic mice. Our study provides evidence that hepatic p38α functions as a negative regulator of AMPK signaling in maintaining gluconeogenesis, dysregulation of this regulatory network contributes to unrestrained gluconeogenesis in diabetes, and hepatic p38α could be a drug target for hyperglycemia. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Trémeau, Fabien; Antonius, Daniel; Todorov, Alexander; Rebani, Yasmina; Ferrari, Kelsey; Lee, Sang Han; Calderone, Daniel; Nolan, Karen A; Butler, Pamela; Malaspina, Dolores; Javitt, Daniel C
2016-04-30
Although social cognition deficits have been associated with schizophrenia, social trait judgments - or first impressions - have rarely been studied. These first impressions, formed immediately after looking at a person's face, have significant social consequences. Eighty-one individuals with schizophrenia or schizoaffective disorder and 62 control subjects rated 30 neutral faces on 10 positive or negative traits: attractive, mean, trustworthy, intelligent, dominant, fun, sociable, aggressive, emotionally stable and weird. Compared to controls, patients gave higher ratings for positive traits as well as for negative traits. Patients also demonstrated more ambivalence in their ratings. Patients who were exhibiting paranoid symptoms assigned higher intensity ratings for positive social traits than non-paranoid patients. Social trait ratings were negatively correlated with everyday problem solving skills in patients. Although patients appeared to form impressions of others in a manner similar to controls, they tended to assign higher scores for both positive and negative traits. This may help explain the social deficits observed in schizophrenia: first impressions of higher degree are harder to correct, and ambivalent attitudes may impair the motivation to interact with others. Consistent with research on paranoia and self-esteem, actively-paranoid patients' positive social traits judgments were of higher intensity than non-paranoid patients'. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer
2005-10-01
overexpressed (Figure 8B). This result is significant for two reasons. First, it provides a mechanistic explanation for how FOXO-1, activated by SIRT1 ...transcription (Figure 4c). This result was confirmed when we used the dominant-negative form of SIRT1 to inhibit its activity (Figure 4d). SIRT-1DN protein... activated by SIRT1 , can act to Figure 3 (a) Androgen increases the IGF-IR protein level in LNCaP. LNCaP cells were grown in the charcoal–dextran
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Autosomal Dominant Growth Hormone Deficiency (Type II).
Alatzoglou, Kyriaki S; Kular, Dalvir; Dattani, Mehul T
2015-06-01
Isolated growth hormone deficiency (IGHD) is the commonest pituitary hormone deficiency resulting from congenital or acquired causes, although for most patients its etiology remains unknown. Among the known factors, heterozygous mutations in the growth hormone gene (GH1) lead to the autosomal dominant form of GHD, also known as type II GHD. In many cohorts this is the commonest form of congenital isolated GHD and is mainly caused by mutations that affect the correct splicing of GH-1. These mutations cause skipping of the third exon and lead to the production of a 17.5-kDa GH isoform that exerts a dominant negative effect on the secretion of the wild type GH. The identification of these mutations has clinical implications for the management of patients, as there is a well-documented correlation between the severity of the phenotype and the increased expression of the 17.5-kDa isoform. Patients with type II GHD have a variable height deficit and severity of GHD and may develop additional pituitary hormone defiencies over time, including ACTH, TSH and gonadotropin deficiencies. Therefore, their lifelong follow-up is recommended. Detailed studies on the effect of heterozygous GH1 mutations on the trafficking, secretion and action of growth hormone can elucidate their mechanism on a cellular level and may influence future treatment options for GHD type II.
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Yokota, Aya; Takeuchi, Emiko; Iizuka, Misao; Ikegami, Yuko; Takayama, Hajime; Shinohara, Nobukata
2005-01-01
Using a panel of transfectant B lymphoma cells expressing varying amounts of the mutant Fas together with the endogenous wild type Fas, semi-quantitative studies on the dominant negative effect of a murine mutant Fas molecule lacking death domain were carried out. In anti-Fas antibody-mediated induction of apoptosis, the mutant molecules exerted significant dominant-negative effect only when their expression level was comparable to or higher than that of wild type molecules, or when exposed to low amounts of the antibody. The inhibitory effect was accompanied by the failure in DISC formation in spite of Fas aggregation. When they were subjected to T cell-mediated Fas-based induction of apoptosis, however, the dominant negative effect was prominent such that the expression of even a small amount of the mutant molecules resulted in significant inhibition. Such a strong inhibitory effect explains the dominant phenotype of this type of mutant Fas molecules in ALPS heterozygous patients and also implies that the physiological effectors for Fas in vivo are cells, i.e., FasL-expressing activated T cells.
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Negative ion formation in potassium-nitromethane collisions.
Antunes, R; Almeida, D; Martins, G; Mason, N J; Garcia, G; Maneira, M J P; Nunes, Y; Limão-Vieira, P
2010-10-21
Ion-pair formation in gaseous nitromethane (CH(3)NO(2)) induced by electron transfer has been studied by investigating the products of collisions between fast potassium atoms and nitromethane molecules using a crossed molecular-beam technique. The negative ions formed in such collisions were analysed using time-of-flight mass spectroscopy. The six most dominant product anions are NO(2)(-), O(-), CH(3)NO(2)(-), OH(-), CH(2)NO(2)(-) and CNO(-). By using nitromethane-d(3) (CD(3)NO(2)), we found that previous mass 17 amu assignment to O(-) delayed fragment, is in the present experiment may be unambiguously assigned to OH(-). The formation of CH(2)NO(2)(-) may be explained in terms of dissociative electron attachment to highly vibrationally excited molecules.
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Experimental study on mechanism and shape characteristics of suspended flexible dam
NASA Astrophysics Data System (ADS)
Wang, Jian-zhong; Fan, Hong-xia; Zhu, Li-jun
2014-12-01
Hydraulic structures such as groin, longitudinal dike and seawall are common in water conservancy and water transportation engineering projects at home and abroad, which have long been dominated by solid mass structural form. With brush and stone as building materials, this kind of structure has an obvious engineering effect. However, it not only requires huge capital investments, but also has negative impacts on the ecological environment. The suspended flexible dam is an innovative engineering measure, and few theoretical and experimental researches of this type dam can be found at present. This paper studies the mechanism and shape characteristics of this dam and obtains the dynamic equilibrium equation of flexible dam, the float buoyancy expression, and the condition for transformation among three forms of the underwater shape of the dam. The results are valuable in engineering application and can be used as the reference for the future work due to the distinctive design philosophy, the small negative effects on environment and the consistency for sustainable development.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Resasco, Julian; et al,
2014-04-01
Abstract. Landscape corridors are commonly used to mitigate negative effects of habitat fragmentation, but concerns persist that they may facilitate the spread of invasive species. In a replicated landscape experiment of open habitat, we measured effects of corridors on the invasive fire ant, Solenopsis invicta, and native ants. Fire ants have two social forms: polygyne, which tend to disperse poorly but establish at high densities, and monogyne, which disperse widely but establish at lower densities. In landscapes dominated by polygyne fire ants, fire ant abundance was higher and native ant diversity was lower in habitat patches connected by corridors thanmore » in unconnected patches. Conversely, in landscapes dominated by monogyne fire ants, connectivity had no influence on fire ant abundance and native ant diversity. Polygyne fire ants dominated recently created landscapes, suggesting that these corridor effects may be transient. Our results suggest that corridors can facilitate invasion and they highlight the importance of considering species’ traits when assessing corridor utility.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Montrose, Kristopher; Krissansen, Geoffrey W., E-mail: gw.krissansen@auckland.ac.nz
Highlights: • A novel proteolysis targeting chimeric molecule (PROTAC) to treat hepatitis B. • The PROTAC antagonizes and destroys the X-protein of the hepatitis B virus. • The PROTAC is a fusion of the X-protein oligomerization and instability domains. • The oligomerization domain is a dominant-negative inhibitor of X-protein function. • X-protein-targeting PROTACs have potential to prevent hepatocellular carcinoma. - Abstract: The X-protein of the hepatitis B virus (HBV) is essential for virus infection and contributes to the development of HBV-induced hepatocellular carcinoma (HCC), a disease which causes more than one million deaths each year. Here we describe the designmore » of a novel PROTAC (proteolysis targeting chimeric molecule) capable of simultaneously inducing the degradation of the X-protein, and antagonizing its function. The PROTAC was constructed by fusing the N-terminal oligomerization and C-terminal instability domains of the X-protein to each other, and rendering them cell-permeable by the inclusion of a polyarginine cell-penetrating peptide (CPP). It was predicted that the oligomerization domain would bind the X-protein, and that the instability domain would cause the X-protein to be targeted for proteasomal degradation. Addition of the PROTAC to HepG2 liver cancer cells, engineered to express full-length and C-terminally truncated forms of the X-protein, resulted in the degradation of both forms of the X-protein. A cell-permeable stand-alone form of the oligomerization domain was taken up by HepG2 cells, and acted as a dominant-negative inhibitor, causing inhibition of X-protein-induced apoptosis. In summary, the PROTAC described here induces the degradation of the X-protein, and antagonizes its function, and warrants investigation in a preclinical study for its ability to prevent or treat HBV infection and/or the development of HCC.« less
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Yeates, Catherine J; Zwiefelhofer, Danielle J; Frank, C Andrew
2017-01-01
Homeostasis is a vital mode of biological self-regulation. The hallmarks of homeostasis for any biological system are a baseline set point of physiological activity, detection of unacceptable deviations from the set point, and effective corrective measures to counteract deviations. Homeostatic synaptic plasticity (HSP) is a form of neuroplasticity in which neurons and circuits resist environmental perturbations and stabilize levels of activity. One assumption is that if a perturbation triggers homeostatic corrective changes in neuronal properties, those corrective measures should be reversed upon removal of the perturbation. We test the reversibility and limits of HSP at the well-studied Drosophila melanogaster neuromuscular junction (NMJ). At the Drosophila NMJ, impairment of glutamate receptors causes a decrease in quantal size, which is offset by a corrective, homeostatic increase in the number of vesicles released per evoked presynaptic stimulus, or quantal content. This process has been termed presynaptic homeostatic potentiation (PHP). Taking advantage of the GAL4/GAL80 TS /UAS expression system, we triggered PHP by expressing a dominant-negative glutamate receptor subunit at the NMJ. We then reversed PHP by halting expression of the dominant-negative receptor. Our data show that PHP is fully reversible over a time course of 48-72 h after the dominant-negative glutamate receptor stops being genetically expressed. As an extension of these experiments, we find that when glutamate receptors are impaired, neither PHP nor NMJ growth is reliably sustained at high culturing temperatures (30-32°C). These data suggest that a limitation of homeostatic signaling at high temperatures could stem from the synapse facing a combination of challenges simultaneously.
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Misra, Maya; Guo, Taomei; Bobb, Susan C.; Kroll, Judith F.
2013-01-01
Behavioral and event-related potential (ERP) measures are reported for a study in which relatively proficient Chinese-English bilinguals named identical pictures in each of their two languages. Production occurred only in Chinese (the first language, L1) or only in English (the second language, L2) in a given block with the order counterbalanced across participants. The repetition of pictures across blocks was expected to produce facilitation in the form of faster responses and more positive ERPs. However, we hypothesized that if both languages are activated when naming one language alone, there might be evidence of inhibition of the stronger L1 to enable naming in the weaker L2. Behavioral data revealed the dominance of Chinese relative to English, with overall faster and more accurate naming performance in L1 than L2. However, reaction times for naming in L1 after naming in L2 showed no repetition advantage and the ERP data showed greater negativity when pictures were named in L1 following L2. This greater negativity for repeated items suggests the presence of inhibition rather than facilitation alone. Critically, the asymmetric negativity associated with the L1 when it followed the L2 endured beyond the immediate switch of language, implying long-lasting inhibition of the L1. In contrast, when L2 naming followed L1, both behavioral and ERP evidence produced a facilitatory pattern, consistent with repetition priming. Taken together, the results support a model of bilingual lexical production in which candidates in both languages compete for selection, with inhibition of the more dominant L1 when planning speech in the less dominant L2. We discuss the implications for modeling the scope and time course of inhibitory processes. PMID:24222718
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Zwiefelhofer, Danielle J.
2017-01-01
Abstract Homeostasis is a vital mode of biological self-regulation. The hallmarks of homeostasis for any biological system are a baseline set point of physiological activity, detection of unacceptable deviations from the set point, and effective corrective measures to counteract deviations. Homeostatic synaptic plasticity (HSP) is a form of neuroplasticity in which neurons and circuits resist environmental perturbations and stabilize levels of activity. One assumption is that if a perturbation triggers homeostatic corrective changes in neuronal properties, those corrective measures should be reversed upon removal of the perturbation. We test the reversibility and limits of HSP at the well-studied Drosophila melanogaster neuromuscular junction (NMJ). At the Drosophila NMJ, impairment of glutamate receptors causes a decrease in quantal size, which is offset by a corrective, homeostatic increase in the number of vesicles released per evoked presynaptic stimulus, or quantal content. This process has been termed presynaptic homeostatic potentiation (PHP). Taking advantage of the GAL4/GAL80TS/UAS expression system, we triggered PHP by expressing a dominant-negative glutamate receptor subunit at the NMJ. We then reversed PHP by halting expression of the dominant-negative receptor. Our data show that PHP is fully reversible over a time course of 48–72 h after the dominant-negative glutamate receptor stops being genetically expressed. As an extension of these experiments, we find that when glutamate receptors are impaired, neither PHP nor NMJ growth is reliably sustained at high culturing temperatures (30–32°C). These data suggest that a limitation of homeostatic signaling at high temperatures could stem from the synapse facing a combination of challenges simultaneously. PMID:29255795
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Tacheau, Charlotte; Fontaine, Juliette; Loy, Jennifer; Mauviel, Alain; Verrecchia, Franck
2008-12-01
One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.
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INTERNALIZATION AND DEGRADATION OF THE GLUTAMATE TRANSPORTER GLT-1 IN RESPONSE TO PHORBOL ESTER
Susarla, Bala T.S.; Robinson, Michael B.
2008-01-01
Activation of protein kinase C (PKC) decreases the activity and cell surface expression of the predominant forebrain glutamate transporter, GLT-1. In the present study, C6 glioma were used as a model system to define the mechanisms that contribute to this decrease in cell surface expression and to determine the fate of internalized transporter. As was previously observed, phorbol 12-myristate 13-acetate (PMA) caused a decrease in biotinylated GLT-1. This effect was blocked by sucrose or by co-expression with a dominant-negative variant of dynamin 1, and it was attenuated by co-expression with a dominant-negative variant of the clathrin heavy chain. Depletion of cholesterol with methyl-β-cyclodextrin, co-expression with a dominant-negative caveolin-1 mutant (Cav1/S80E), co-expression with dominant-negative variants of Eps15 (epidermal-growth-factor receptor pathway substrate clone 15), or co-expression with dominant-negative Arf6 (T27N) had no effect on the PMA-induced loss of biotinylated GLT-1. Long-term treatment with PMA caused a time-dependent loss of biotinylated GLT-1 and decreased the levels of GLT-1 protein. Inhibitors of lysosomal degradation (chloroquine or ammonium chloride) or co-expression with a dominant-negative variant of a small GTPase implicated in trafficking to lysosomes (Rab7) prevented the PMA-induced decrease in protein and caused an intracellular accumulation of GLT-1. These results suggest that the PKC-induced redistribution of GLT-1 is dependent upon clathrin-mediated endocytosis. These studies identify a novel mechanism by which the levels of GLT-1 could be rapidly down-regulated via lysosomal degradation. The possibility that this mechanism may contribute to the loss of GLT-1 observed after acute insults to the CNS is discussed. PMID:17919781
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Combinatorial events of insertion sequences and ICE in Gram-negative bacteria.
Toleman, Mark A; Walsh, Timothy R
2011-09-01
The emergence of antibiotic and antimicrobial resistance in Gram-negative bacteria is incremental and linked to genetic elements that function in a so-called 'one-ended transposition' manner, including ISEcp1, ISCR elements and Tn3-like transposons. The power of these elements lies in their inability to consistently recognize one of their own terminal sequences, while recognizing more genetically distant surrogate sequences. This has the effect of mobilizing the DNA sequence found adjacent to their initial location. In general, resistance in Gram-negatives is closely linked to a few one-off events. These include the capture of the class 1 integron by a Tn5090-like transposon; the formation of the 3' conserved segment (3'-CS); and the fusion of the ISCR1 element to the 3'-CS. The structures formed by these rare events have been massively amplified and disseminated in Gram-negative bacteria, but hitherto, are rarely found in Gram-positives. Such events dominate current resistance gene acquisition and are instrumental in the construction of large resistance gene islands on chromosomes and plasmids. Similar combinatorial events appear to have occurred between conjugative plasmids and phages constructing hybrid elements called integrative and conjugative elements or conjugative transposons. These elements are beginning to be closely linked to some of the more powerful resistance mechanisms such as the extended spectrum β-lactamases, metallo- and AmpC type β-lactamases. Antibiotic resistance in Gram-negative bacteria is dominated by unusual combinatorial mistakes of Insertion sequences and gene fusions which have been selected and amplified by antibiotic pressure enabling the formation of extended resistance islands. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Cheng, Sy-Chyi; Bhat, Suhail Muzaffar; Shiea, Jentaie
2017-07-01
Flame atmospheric pressure chemical ionization (FAPCI) combined with negative electrospray ionization (ESI) mass spectrometry was developed to detect the ion/molecule reactions (IMRs) products between nitric acid (HNO3) and negatively charged amino acid, angiotensin I (AI) and angiotensin II (AII), and insulin ions. Nitrate and HNO3-nitrate ions were detected in the oxyacetylene flame, suggesting that a large quantity of nitric acid (HNO3) was produced in the flame. The HNO3 and negatively charged analyte ions produced by a negative ESI source were delivered into each arm of a Y-shaped stainless steel tube where they merged and reacted. The products were subsequently characterized with an ion trap mass analyzer attached to the exit of the Y-tube. HNO3 showed the strongest affinity to histidine and formed (Mhistidine-H+HNO3)- complex ions, whereas some amino acids did not react with HNO3 at all. Reactions between HNO3 and histidine residues in AI and AII resulted in the formation of dominant [MAI-H+(HNO3)]- and [MAII-H+(HNO3)]- ions. Results from analyses of AAs and insulin indicated that HNO3 could not only react with basic amino acid residues, but also with disulfide bonds to form [M-3H+(HNO3)n]3- complex ions. This approach is useful for obtaining information about the number of basic amino acid residues and disulfide bonds in peptides and proteins.
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Selective resputtering of bismuth in sputtered Bi-Sr-Ca-Cu-O films
NASA Astrophysics Data System (ADS)
Grace, J. M.; McDonald, D. B.; Reiten, M. T.; Olson, J.; Kampwirth, R. T.; Gray, K. E.
1991-10-01
We present studies using a dc magnetron in an on-axis configuration to sputter Bi-Sr-Ca-Cu-O films from a composite target. These studies show that bismuth can be preferentially resputtered. The influence of ozone, molecular oxygen, and total pressure on the resputtering of bismuth is investigated and discussed. Ozone, in low concentrations, can dramatically affect the degree of resputtering. By comparing the effects of molecular oxygen and ozone, some insight is gained regarding the possible mechanisms of negative ion formation in the magnetron environment. Based on our results we suggest that molecular oxygen can bring about resputtering primarily by forming O+2, which collides with the target to produce energetic negative oxygen ions. In contrast, ozone may form negative ions by electron impact in the dark space above the target, giving rise to lower-energy negative ions, which can traverse the plasma unneutralized and can be stopped with an applied bias on the sample block. With no added oxidant, negative oxygen ions from the target oxygen may dominate the background resputtering. Similarity is found between our results and those for similar studies on Y-Ba-Cu-O by other workers. Bismuth in Bi-Sr-Ca-Cu-O behaves as barium in Y-Ba-Cu-O with regards to preferential resputtering; furthermore, the response of strontium, calcium, and copper to oxygen in sputtered Bi-Sr-Ca-Cu-O is similar to what is observed for copper in Y-Ba-Cu-O.
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Cheng, Sy-Chyi; Bhat, Suhail Muzaffar; Shiea, Jentaie
2017-07-01
Flame atmospheric pressure chemical ionization (FAPCI) combined with negative electrospray ionization (ESI) mass spectrometry was developed to detect the ion/molecule reactions (IMRs) products between nitric acid (HNO 3 ) and negatively charged amino acid, angiotensin I (AI) and angiotensin II (AII), and insulin ions. Nitrate and HNO 3 -nitrate ions were detected in the oxyacetylene flame, suggesting that a large quantity of nitric acid (HNO 3 ) was produced in the flame. The HNO 3 and negatively charged analyte ions produced by a negative ESI source were delivered into each arm of a Y-shaped stainless steel tube where they merged and reacted. The products were subsequently characterized with an ion trap mass analyzer attached to the exit of the Y-tube. HNO 3 showed the strongest affinity to histidine and formed (M histidine -H+HNO 3 ) - complex ions, whereas some amino acids did not react with HNO 3 at all. Reactions between HNO 3 and histidine residues in AI and AII resulted in the formation of dominant [M AI -H+(HNO 3 )] - and [M AII -H+(HNO 3 )] - ions. Results from analyses of AAs and insulin indicated that HNO 3 could not only react with basic amino acid residues, but also with disulfide bonds to form [M-3H+(HNO 3 ) n ] 3- complex ions. This approach is useful for obtaining information about the number of basic amino acid residues and disulfide bonds in peptides and proteins. Graphical Abstract ᅟ.
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Irion, Uwe; Frohnhöfer, Hans Georg; Krauss, Jana; Çolak Champollion, Tuǧba; Maischein, Hans-Martin; Geiger-Rudolph, Silke; Weiler, Christian; Nüsslein-Volhard, Christiane
2014-01-01
Interactions between all three pigment cell types are required to form the stripe pattern of adult zebrafish (Danio rerio), but their molecular nature is poorly understood. Mutations in leopard (leo), encoding Connexin 41.8 (Cx41.8), a gap junction subunit, cause a phenotypic series of spotted patterns. A new dominant allele, leotK3, leads to a complete loss of the pattern, suggesting a dominant negative impact on another component of gap junctions. In a genetic screen, we identified this component as Cx39.4 (luchs). Loss-of-function alleles demonstrate that luchs is required for stripe formation in zebrafish; however, the fins are almost not affected. Double mutants and chimeras, which show that leo and luchs are only required in xanthophores and melanophores, but not in iridophores, suggest that both connexins form heteromeric gap junctions. The phenotypes indicate that these promote homotypic interactions between melanophores and xanthophores, respectively, and those cells instruct the patterning of the iridophores. DOI: http://dx.doi.org/10.7554/eLife.05125.001 PMID:25535837
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Reith, A D; Ellis, C; Maroc, N; Pawson, T; Bernstein, A; Dubreuil, P
1993-01-01
Point mutations in highly conserved amino acid residues in the catalytic domain of the Kit receptor tyrosine kinase (RTK) are responsible for the coat color, fertility and hematopoietic defects of mice bearing mutant alleles at the dominant white-spotting (W) locus. The dominant nature of structural Kit mutations suggests that expression of other kinase-defective RTKs might also specifically interfere with signal transduction by normal receptors. To test this possibility, we have investigated the functional consequences of introducing analogous mutations into the RTK encoded by the c-fms proto-oncogene. Both Fms37 (glu582-->lys) and Fms42 (asp776-->asn) mutant proteins, corresponding to the strongly dominant-negative W37 and W42 mutant c-kit alleles, had undetectable in vitro kinase activity and were unable to transform Rat-2 fibroblasts in the presence of exogenous CSF-1. Moreover, expression of Fms37 or Fms42 proteins in Rat-2 cells specifically inhibited anchorage-independent growth mediated by the normal Fms receptor in the presence of exogenous CSF-1 and conferred a dominant loss of Fms-associated PI3-kinase activity on CSF-1 stimulation. Mutant RTKs, bearing point substitutions identical to those present in mild or severe W mutants, may provide a generally applicable strategy for inducing dominant loss of function defects in RTK-mediated signalling pathways.
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Negative frequency-dependent selection between Pasteuria penetrans and its host Meloidogyne arenaria
USDA-ARS?s Scientific Manuscript database
In negative frequency-dependant selection (NFDS), parasite genotypes capable of infecting the numerically dominant host genotype are favored, while host genotypes resistant to the dominant parasite genotype are favored, creating a cyclical pattern of resistant genotypes in the host population and, a...
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Selective Suppression of Endothelial Cell Apoptosis by the High Molecular Weight Form of Adiponectin
Kobayashi, Hideki; Ouchi, Noriyuki; Kihara, Shinji; Walsh, Kenneth; Kumada, Masahiro; Abe, Yuki; Funahashi, Tohru; Matsuzawa, Yuji
2015-01-01
Adiponectin is an adipocyte-derived, antiatherogenic protein that is present in serum as three isoforms. Total adiponectin levels are decreased in obese or diabetic humans or animal models. This study was designed to elucidate the relative isoform distribution of adiponectin in human disease states and identify the active form of adiponectin toward vascular endothelial cells. The percentage of high molecular weight form (HMW) per total adiponectin was significantly lower in patients with coronary artery disease than control subjects, whereas the hexamer form was similar and the trimer form was significantly higher. During weight reduction in obese subjects, the HMW form increased and the trimer and hexamer forms decreased. Recombinant adiponectin dose-dependently suppressed apoptosis and caspase-3 activity in human umbilical vein endothelial cells (HUVECs). Transduction with dominant-negative AMP-activated protein kinase (AMPK) abolished the suppressive effect of adiponectin on HUVECs. Gel filtration chromatography was used to separate the adiponectin isoforms, and the antiapoptotic effect toward HUVECs was only observed with the HMW form. These data suggest that HMW adiponectin specifically confers the vascular-protective activities of this adipocytokine. PMID:14752031
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Dantas, Vitor G L; Raval, Manmeet H; Ballesteros, Angela; Cui, Runjia; Gunther, Laura K; Yamamoto, Guilherme L; Alves, Leandro Ucela; Bueno, André Silva; Lezirovitz, Karina; Pirana, Sulene; Mendes, Beatriz C A; Yengo, Christopher M; Kachar, Bechara; Mingroni-Netto, Regina C
2018-06-07
Whole-exome sequencing of samples from affected members of two unrelated families with late-onset non-syndromic hearing loss revealed a novel mutation (c.2090 T > G; NM_017433) in MYO3A. The mutation was confirmed in 36 affected individuals, showing autosomal dominant inheritance. The mutation alters a single residue (L697W or p.Leu697Trp) in the motor domain of the stereocilia protein MYO3A, leading to a reduction in ATPase activity, motility, and an increase in actin affinity. MYO3A-L697W showed reduced filopodial actin protrusion initiation in COS7 cells, and a predominant tipward accumulation at filopodia and stereocilia when coexpressed with wild-type MYO3A and espin-1, an actin-regulatory MYO3A cargo. The combined higher actin affinity and duty ratio of the mutant myosin cause increased retention time at stereocilia tips, resulting in the displacement of the wild-type MYO3A protein, which may impact cargo transport, stereocilia length, and mechanotransduction. The dominant negative effect of the altered myosin function explains the dominant inheritance of deafness.
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Langsrud, S; Moen, B; Møretrø, T; Løype, M; Heir, E
2016-02-01
The microbiota surviving sanitation of salmon-processing conveyor belts was identified and its growth dynamics further investigated in a model mimicking processing surfaces in such plants. A diverse microbiota dominated by Gram-negative bacteria was isolated after regular sanitation in three salmon processing plants. A cocktail of 14 bacterial isolates representing all genera isolated from conveyor belts (Listeria, Pseudomonas, Stenotrophomonas, Brochothrix, Serratia, Acinetobacter, Rhodococcus and Chryseobacterium) formed stable biofilms on steel coupons (12°C, salmon broth) of about 10(9) CFU cm(-2) after 2 days. High-throughput sequencing showed that Listeria monocytogenes represented 0·1-0·01% of the biofilm population and that Pseudomonas spp dominated. Interestingly, both Brochothrix sp. and a Pseudomonas sp. dominated in the surrounding suspension. The microbiota surviving sanitation is dominated by Pseudomonas spp. The background microbiota in biofilms inhibit, but do not eliminate L. monocytogenes. The results highlights that sanitation procedures have to been improved in the salmon-processing industry, as high numbers of a diverse microbiota survived practical sanitation. High-throughput sequencing enables strain level studies of population dynamics in biofilm. © 2015 The Society for Applied Microbiology.
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Culiver, Adam; Garrison, J Craig; Creed, Kalyssa M; Conway, John E; Goto, Shiho; Werner, Sherry
2018-01-24
Numerous studies have reported kinematic data on baseball pitchers using 3D motion analysis, but no studies to date have correlated this data with clinical outcome measures. To examine the relationship among Y Balance Test-Lower Quarter (YBT-LQ) composite scores, musculoskeletal characteristics of the hip and pitching kinematics in NCAA Division I baseball pitchers. Cross-sectional. 3D motion analysis laboratory. 19 healthy male collegiate baseball pitchers. Internal and external hip passive range of motion (PROM); hip abduction strength; YBT-LQ composite scores; kinematic variables of the pitching motion. Stride length demonstrated a moderate positive correlation with dominant limb YBT-LQ composite score (r=0.524, p=0.018) and non-dominant limb YBT-LQ composite score (r=0.550, p=0.012), and a weak positive correlation with normalized time to maximal humerus velocity (r=0.458, p=0.043). Stride length had a moderate negative correlation with normalized time to maximal thorax velocity (r= -0.522, p=0.018) and dominant hip TRM (r= -0.660, p=0.002), and had a strong negative correlation with normalized time from SFC to maximal knee flexion (r= -0.722, p<0.001). Dominant limb YBT-LQ composite score had a weak negative correlation with hip abduction strength difference (r= -0.459, p=0.042) and normalized time to maximal thorax velocity (r= -0.468, p=0.037), as well as a moderate negative correlation with dominant hip TRM (r= -0.160, p=0.004). Non-dominant limb YBT-LQ composite score demonstrated a weak negative correlation with normalized time to maximal thorax velocity (r= -0.450, p=0.046) and had a moderate negative correlation with dominant hip TRM (r= -0.668, p=0.001). Hip abduction strength difference demonstrated a weak positive correlation with dominant hip TRM (r=0.482, p=0.032). Dominant hip TRM had a moderate positive correlation with normalized time to maximal thorax velocity (r=0.484, p=0.031). There were no other significant relationships between the remaining variables. YBT-LQ is a clinical measure which can be used to correlate with hip musculoskeletal characteristics and pitching kinematics in NCAA Division I pitchers.
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Nunes, Paula; Haines, Nicola; Kuppuswamy, Venkat; Fleet, David J.
2006-01-01
N-ethylmaleimide sensitive factor (NSF) can dissociate the soluble NSF attachment receptor (SNARE) complex, but NSF also participates in other intracellular trafficking functions by virtue of SNARE-independent activity. Drosophila that express a neural transgene encoding a dominant-negative form of NSF2 show an 80% reduction in the size of releasable synaptic vesicle pool, but no change in the number of vesicles in nerve terminal boutons. Here we tested the hypothesis that vesicles in the NSF2 mutant terminal are less mobile. Using a combination of genetics, pharmacology, and imaging we find a substantial reduction in vesicle mobility within the nerve terminal boutons of Drosophila NSF2 mutant larvae. Subsequent analysis revealed a decrease of filamentous actin in both NSF2 dominant-negative and loss-of-function mutants. Lastly, actin-filament disrupting drugs also decrease vesicle movement. We conclude that a factor contributing to the NSF mutant phenotype is a reduction in vesicle mobility, which is associated with decreased presynaptic F-actin. Our data are consistent with a model in which actin filaments promote vesicle mobility and suggest that NSF participates in establishing or maintaining this population of actin. PMID:16914524
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NASA Astrophysics Data System (ADS)
Campbell, Timothy; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya; Ogata, Shuji; Rodgers, Stephen
1999-06-01
Oxidation of aluminum nanoclusters is investigated with a parallel molecular-dynamics approach based on dynamic charge transfer among atoms. Structural and dynamic correlations reveal that significant charge transfer gives rise to large negative pressure in the oxide which dominates the positive pressure due to steric forces. As a result, aluminum moves outward and oxygen moves towards the interior of the cluster with the aluminum diffusivity 60% higher than that of oxygen. A stable 40 Å thick amorphous oxide is formed; this is in excellent agreement with experiments.
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The Sound of Dominance: Vocal Precursors of Perceived Dominance during Interpersonal Influence.
ERIC Educational Resources Information Center
Tusing, Kyle James; Dillard, James Price
2000-01-01
Determines the effects of vocal cues on judgments of dominance in an interpersonal influence context. Indicates that mean amplitude and amplitude standard deviation were positively associated with dominance judgments, whereas speech rate was negatively associated with dominance judgments. Finds that mean fundamental frequency was positively…
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Alpine treeline of western North America: Linking organism-to-landscape dynamics
Malanson, George P.; Butler, David R.; Fagre, Daniel B.; Walsh, Stephen J; Tomback, Diana F.; Daniels, Lori D.; Resler, Lynn M.; Smith, William K.; Weiss, Daniel J.; Peterson, David L.; Bunn, Andrew G.; Hiemstra, Christopher A.; Liptzin, Daniel; Bourgeron, Patrick S.; Shen, Zehao; Millar, Constance I.
2007-01-01
Although the ecological dynamics of the alpine treeline ecotone are influenced by climate, it is an imperfect indicator of climate change. Mechanistic processes that shape the ecotone—seed rain, seed germination, seedling establishment and subsequent tree growth form, or, conversely tree dieback—depend on microsite patterns. Growth forms affect wind and snow, and so develop positive and negative feedback loops that create these microsites. As a result, complex landscape patterns are generated at multiple spatial scales. Although these mechanistic processes are fundamentally the same for all forest-tundra ecotones across western North America, factors such as prior climate, underlying geology and geomorphology, and genetic constraints of dominant tree species lead to geographic differences in the responses of particular ecotones to climate change.
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Gorynia, Inge; Schwaiger, Markus; Heinz, Andreas
2014-12-01
Based on the previous findings, it has been assumed that in schizophrenia patients, eye dominance and cannabis use will affect negative symptoms and intermanual coordination (IMC), an index of interhemispheric communication. But eye dominance, specifically the clinical findings for it, has been neglected in schizophrenia research. We therefore investigated its effects in 52 right-handed (36 right-eyed and 16 left-eyed) and 51 left-handed (35 left-eyed and 16 right-eyed) schizophrenia in-patients without and with drug use. Eye dominance affected IMC in all schizophrenia patients. When comparing right- and left-handers, we found that this result was only significant in the right-handed patients and in the smaller subgroup without drug use. In the right-handers, left eye dominance-like left-handedness-was associated with higher values in IMC and less pronounced manifestation of negative symptoms, right eye dominance was not. Thus, left-eyed right-handers may be more closely related to left-handers than to right-handers. In accordance with the results from the literature, we suggest that these findings are due to better interhemispheric connections and less impairment of white matter structures, especially in right-hemispheric regions. Moreover, cannabis use was related to higher scores in IMC and less pronounced negative symptoms, but only in the right-eyed and not in the left-eyed right-handers or in the left-handers. Hence, differences in eye dominance and handedness may be partially responsible for different results in interhemispheric connections among cannabis users. In conclusion, both eye dominance and use of cannabis should be taken into account when assessing clinical symptoms in schizophrenia patients.
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How Power Mechanism Influence Channel Bilateral Opportunism
NASA Astrophysics Data System (ADS)
Tian, Yu; Chen, Shaodan
In the background of marketing channel power asymmetry structure, this article discuss the relation between power dominant member’s use of power mechanism and the opportunism behavior of both Power disadvantage member and the power dominant member itself, and test whether distributive fairness perception and procedural fairness perception have moderate effects on this relation. The result shows that, the power dominant member’s use of coercive power will increase the opportunistic tendency of both sides; in contrast, the power dominant member’s use of noncorecive power will inhibit such tendency. Distributive fairness perception and procedural fairness perception negatively moderate the relation between power dominant member’s use of noncorecive power and power disadvantage member’s opportunism. Procedural fairness perception also negatively moderates the relation between power dominant member’s use of coercive power and the other side’s opportunism.
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The structural basis of the dominant negative phenotype of the Gαi1β1γ2 G203A/A326S heterotrimer
Liu, Ping; Jia, Ming-zhu; Zhou, X Edward; De Waal, Parker W; Dickson, Bradley M; Liu, Bo; Hou, Li; Yin, Yan-ting; Kang, Yan-yong; Shi, Yi; Melcher, Karsten; Xu, H Eric; Jiang, Yi
2016-01-01
Aim: Dominant negative mutant G proteins have provided critical insight into the mechanisms of G protein-coupled receptor (GPCR) signaling, but the mechanisms underlying the dominant negative characteristics are not completely understood. The aim of this study was to determine the structure of the dominant negative Gαi1β1γ2 G203A/A326S complex (Gi-DN) and to reveal the structural basis of the mutation-induced phenotype of Gαi1β1γ2. Methods: The three subunits of the Gi-DN complex were co-expressed with a baculovirus expression system. The Gi-DN heterotrimer was purified, and the structure of its complex with GDP was determined through X-ray crystallography. Results: The Gi-DN heterotrimer structure revealed a dual mechanism underlying the dominant negative characteristics. The mutations weakened the hydrogen bonding network between GDP/GTP and the binding pocket residues, and increased the interactions in the Gα-Gβγ interface. Concomitantly, the Gi-DN heterotrimer adopted a conformation, in which the C-terminus of Gαi and the N-termini of both the Gβ and Gγ subunits were more similar to the GPCR-bound state compared with the wild type complex. From these structural observations, two additional mutations (T48F and D272F) were designed that completely abolish the GDP binding of the Gi-DN heterotrimer. Conclusion: Overall, the results suggest that the mutations impede guanine nucleotide binding and Gα-Gβγ protein dissociation and favor the formation of the G protein/GPCR complex, thus blocking signal propagation. In addition, the structure provides a rationale for the design of other mutations that cause dominant negative effects in the G protein, as exemplified by the T48F and D272F mutations. PMID:27498775
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Fitzgerald, Kerry D.; Semler, Bert L.
2013-01-01
Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. PMID:23830997
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Sabourin, Jessica; Le Gal, Loïc; Saurwein, Lisa; Haefliger, Jacques-Antoine; Raddatz, Eric; Allagnat, Florent
2015-01-01
Store-operated Ca2+ channels (SOCs) are voltage-independent Ca2+ channels activated upon depletion of the endoplasmic reticulum Ca2+ stores. Early studies suggest the contribution of such channels to Ca2+ homeostasis in insulin-secreting pancreatic β-cells. However, their composition and contribution to glucose-stimulated insulin secretion (GSIS) remains unclear. In this study, endoplasmic reticulum Ca2+ depletion triggered by acetylcholine (ACh) or thapsigargin stimulated the formation of a ternary complex composed of Orai1, TRPC1, and STIM1, the key proteins involved in the formation of SOCs. Ca2+ imaging further revealed that Orai1 and TRPC1 are required to form functional SOCs and that these channels are activated by STIM1 in response to thapsigargin or ACh. Pharmacological SOCs inhibition or dominant negative blockade of Orai1 or TRPC1 using the specific pore mutants Orai1-E106D and TRPC1-F562A impaired GSIS in rat β-cells and fully blocked the potentiating effect of ACh on secretion. In contrast, pharmacological or dominant negative blockade of TRPC3 had no effect on extracellular Ca2+ entry and GSIS. Finally, we observed that prolonged exposure to supraphysiological glucose concentration impaired SOCs function without altering the expression levels of STIM1, Orai1, and TRPC1. We conclude that Orai1 and TRPC1, which form SOCs regulated by STIM1, play a key role in the effect of ACh on GSIS, a process that may be impaired in type 2 diabetes. PMID:26494622
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Rosenthal-Stott, Harriet E. S.; Dicks, Rea E.; Fielding, Lois S.
2015-01-01
We examined whether self-generated (status updates) or other-generated (wall-posts) information on Facebook influenced the impression formed of the target individual. Along with examining reliance on particular types of information, we explored the valence (positive/ neutral/ negative) of the information, as reliance on self-generated or other-generated information may depend on whether self-presentation is perceived (i.e., presenting oneself positively / not negatively). Self-presentation may be perceived if the targets have positive/ neutral statuses, while negative statuses would indicate a lack of self-presentation. In line with previous research, participants should rely on other-generated information (wall-posts) to form an impression when participants are viewed to have self-presented (positive / neutral status updates), as this information could be viewed as unreliable. Forty participants rated nine Facebook profiles where statuses and wall-posts portrayed personality traits varying in valence. Each profile consisted of a neutral profile photo, three status updates (all positive, negative, or neutral) and three wall-posts (all positive, negative, or neutral). Materials were established in two pilots. Impression formation was measured as perceived social, task, and physical attractiveness of the target individual. Participants also ranked the profiles for likeability. Supporting our expectations, other-generated information (wall-posts) dominated impression formation for social attractiveness when self-generated information (status updates) was positive/ neutral. Task attractiveness was affected by information valence, regardless of source (self or other). Despite the inclusion of neutral photos, physical attractiveness was affected by self-generated information, with negative statuses lowering physical attractiveness. We suggest that these findings have implications for impression formation beyond the Facebook setting. The 557 traits analyzed in Pilot 1 are available as supporting information (S1 Dataset) and may be useful for other impression formation researchers. PMID:26087032
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Advection-dominated Inflow/Outflows from Evaporating Accretion Disks.
Turolla; Dullemond
2000-03-01
In this Letter we investigate the properties of advection-dominated accretion flows (ADAFs) fed by the evaporation of a Shakura-Sunyaev accretion disk (SSD). In our picture, the ADAF fills the central cavity evacuated by the SSD and extends beyond the transition radius into a coronal region. We find that, because of global angular momentum conservation, a significant fraction of the hot gas flows away from the black hole, forming a transsonic wind, unless the injection rate depends only weakly on radius (if r2sigma&d2;~r-xi, xi<1&solm0;2). The Bernoulli number of the inflowing gas is negative if the transition radius is less, similar100 Schwarzschild radii, so matter falling into the hole is gravitationally bound. The ratio of inflowing to outflowing mass is approximately 1/2, so in these solutions the accretion rate is of the same order as in standard ADAFs and much larger than in advection-dominated inflow/outflow models. The possible relevance of evaporation-fed solutions to accretion flows in black hole X-ray binaries is briefly discussed.
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Yool, Andrea J
2007-01-01
The neurogenic protein Drosophila big brain (BIB), which is involved in the process of neuroblast determination, and the water channel aquaporin-1 (AQP1) are among a subset of the major intrinsic protein (MIP) channels that have been found to show gated monovalent cation channel activity. A glutamate residue in the first transmembrane (M1) domain is conserved throughout the MIP family. Mutation of this residue to asparagine in BIB (E71N) knocks out ion channel activity, and when coexpressed with BIB wild-type as shown here generates a dominant-negative effect on ion channel function, measured in the Xenopus oocyte expression system using two-electrode voltage clamp. cRNAs for wild-type and mutant BIB or AQP1 channels were injected individually or as mixtures. The magnitude of the BIB ionic conductance response was greatly reduced by coexpression of the mutant E71N subunit, suggesting a dominant-negative mechanism of action. The analogous mutation in AQP1 (E17N) did not impair ion channel activation by cGMP, but did knock out water channel function, although not via a dominant-negative effect. This contrast in sensitivity between BIB and AQP1 to mutation of the M1 glutamate suggests the possibility of interesting structural differences in the molecular basis of the ion permeation between these two classes of channels. The dominant-negative construct of BIB could be a tool for testing a role for BIB ion channels during nervous system development in Drosophila. The neurogenic protein Drosophila big brain (BIB), which is involved in the process of neuroblast determination, and the water channel aquaporin-1 (AQP1) are among a subset of the major intrinsic protein (MIP) channels that have been found to show gated monovalent cation channel activity. A glutamate residue in the first transmembrane (M1) domain is conserved throughout the MIP family. Mutation of this residue to asparagine in BIB (E71N) knocks out ion channel activity, and when coexpressed with BIB wild-type as shown here generates a dominant-negative effect on ion channel function, measured in the Xenopus oocyte expression system using two-electrode voltage clamp. cRNAs for wild-type and mutant BIB or AQP1 channels were injected individually or as mixtures. The magnitude of the BIB ionic conductance response was greatly reduced by coexpression of the mutant E71N subunit, suggesting a dominant-negative mechanism of action. The analogous mutation in AQP1 (E17N) did not impair ion channel activation by cGMP, but did knock out water channel function, although not via a dominant-negative effect. This contrast in sensitivity between BIB and AQP1 to mutation of the M1 glutamate suggests the possibility of interesting structural differences in the molecular basis of the ion permeation between these two classes of channels. The dominant-negative construct of BIB could be a tool for testing a role for BIB ion channels during nervous system development in Drosophila.
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Racism and Health I: Pathways and Scientific Evidence.
Williams, David R; Mohammed, Selina A
2013-08-01
This article reviews the scientific research that indicates that despite marked declines in public support for negative racial attitudes in the United States, racism, in its multiple forms, remains embedded in American society. The focus of the article is on the review of empirical research that suggests that racism adversely affects the health of non-dominant racial populations in multiple ways. First, institutional racism developed policies and procedures that have reduced access to housing, neighborhood and educational quality, employment opportunities and other desirable resources in society. Second, cultural racism, at the societal and individual level, negatively affects economic status and health by creating a policy environment hostile to egalitarian policies, triggering negative stereotypes and discrimination that are pathogenic and fostering health damaging psychological responses such as stereotype threat and internalized racism. Finally, a large and growing body of evidence indicates that experiences of racial discrimination are an important type of psychosocial stressor that can lead to adverse changes in health status and altered behavioural patterns that increase health risks.
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Racism and Health I: Pathways and Scientific Evidence
Williams, David R.; Mohammed, Selina A.
2013-01-01
This article reviews the scientific research that indicates that despite marked declines in public support for negative racial attitudes in the United States, racism, in its multiple forms, remains embedded in American society. The focus of the article is on the review of empirical research that suggests that racism adversely affects the health of non-dominant racial populations in multiple ways. First, institutional racism developed policies and procedures that have reduced access to housing, neighborhood and educational quality, employment opportunities and other desirable resources in society. Second, cultural racism, at the societal and individual level, negatively affects economic status and health by creating a policy environment hostile to egalitarian policies, triggering negative stereotypes and discrimination that are pathogenic and fostering health damaging psychological responses such as stereotype threat and internalized racism. Finally, a large and growing body of evidence indicates that experiences of racial discrimination are an important type of psychosocial stressor that can lead to adverse changes in health status and altered behavioural patterns that increase health risks. PMID:24347666
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Gender differences in experiences of sexual harassment: data from a male-dominated environment.
Street, Amy E; Gradus, Jaimie L; Stafford, Jane; Kelly, Kacie
2007-06-01
The goal of this investigation was to examine gender differences in experiences of sexual harassment during military service and the negative mental health symptoms associated with these experiences. Female (n = 2,319) and male (n = 1,627) former reservists were surveyed about sexual harassment during their military service and current mental health symptoms. As expected, women reported a higher frequency of sexual harassment. Further, women had increased odds of experiencing all subtypes of sexual harassment. Being female conferred the greatest risk for experiencing the most serious forms of harassment. For both men and women, sexual harassment was associated with more negative current mental health. However, at higher levels of harassment, associations with some negative mental health symptoms were stronger for men than women. Although preliminary, the results of this investigation suggest that although women are harassed more frequently than men, clinicians must increase their awareness of the potential for sexual harassment among men in order to provide the best possible care to all victims of harassment. Copyright 2007 APA.
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Yakubchyk, Yury; Abramovici, Hanan; Maillet, Jean-Christian; Daher, Elias; Obagi, Christopher; Parks, Robin J.; Topham, Matthew K.; Gee, Stephen H.
2005-01-01
Syntrophins are scaffold proteins that regulate the subcellular localization of diacylglycerol kinase ζ (DGK-ζ), an enzyme that phosphorylates the lipid second-messenger diacylglycerol to yield phosphatidic acid. DGK-ζ and syntrophins are abundantly expressed in neurons of the developing and adult brain, but their function is unclear. Here, we show that they are present in cell bodies, neurites, and growth cones of cultured cortical neurons and differentiated N1E-115 neuroblastoma cells. Overexpression of DGK-ζ in N1E-115 cells induced neurite formation in the presence of serum, which normally prevents neurite outgrowth. This effect was independent of DGK-ζ kinase activity but dependent on a functional C-terminal PDZ-binding motif, which specifically interacts with syntrophin PDZ domains. DGK-ζ mutants with a blocked C terminus acted as dominant-negative inhibitors of outgrowth from serum-deprived N1E-115 cells and cortical neurons. Several lines of evidence suggest DGK-ζ promotes neurite outgrowth through association with the GTPase Rac1. DGK-ζ colocalized with Rac1 in neuronal processes and DGK-ζ-induced outgrowth was inhibited by dominant-negative Rac1. Moreover, DGK-ζ directly interacts with Rac1 through a binding site located within its C1 domains. Together with syntrophin, these proteins form a tertiary complex in N1E-115 cells. A DGK-ζ mutant that mimics phosphorylation of the MARCKS domain was unable to bind an activated Rac1 mutant (Rac1V12) and phorbol myristate acetate-induced protein kinase C activation inhibited the interaction of DGK-ζ with Rac1V12, suggesting protein kinase C-mediated phosphorylation of the MARCKS domain negatively regulates DGK-ζ binding to active Rac1. Collectively, these findings suggest DGK-ζ, syntrophin, and Rac1 form a regulated signaling complex that controls polarized outgrowth in neuronal cells. PMID:16055737
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An image is worth a thousand words: why nouns tend to dominate verbs in early word learning.
McDonough, Colleen; Song, Lulu; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick; Lannon, Robert
2011-03-01
Nouns are generally easier to learn than verbs (e.g., Bornstein, 2005; Bornstein et al., 2004; Gentner, 1982; Maguire, Hirsh-Pasek, & Golinkoff, 2006). Yet, verbs appear in children's earliest vocabularies, creating a seeming paradox. This paper examines one hypothesis about the difference between noun and verb acquisition. Perhaps the advantage nouns have is not a function of grammatical form class but rather related to a word's imageability. Here, word imageability ratings and form class (nouns and verbs) were correlated with age of acquisition according to the MacArthur-Bates Communicative Development Inventory (CDI) (Fenson et al., 1994). CDI age of acquisition was negatively correlated with words' imageability ratings. Further, a word's imageability contributes to the variance of the word's age of acquisition above and beyond form class, suggesting that at the beginning of word learning, imageability might be a driving factor.
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Russler-Germain, David A.; Spencer, David H.; Young, Margaret A.; Lamprecht, Tamara L.; Miller, Christopher A.; Fulton, Robert; Meyer, Matthew R.; Erdmann-Gilmore, Petra; Townsend, R. Reid; Wilson, Richard K.; Ley, Timothy J.
2014-01-01
Summary Somatic mutations in DNMT3A, which encodes a de novo DNA methyltransferase, are found in ~30% of normal karyotype acute myeloid leukemia (AML) cases. Most mutations are heterozygous and alter R882 within the catalytic domain (most commonly R882H), suggesting the possibility of dominant negative consequences. The methyltransferase activity of R882H DNMT3A is reduced by ~80% compared to the WT enzyme. In vitro mixing of WT and R882H DNMT3A does not affect the WT activity but co-expression of the two proteins in cells profoundly inhibits the WT enzyme by disrupting its ability to homotetramerize. AML cells with the R882H mutation have severely reduced de novo methyltransferase activity and focal hypomethylation at specific CpGs throughout AML cell genomes. PMID:24656771
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Measurement of the Drell-Yan angular distribution in the dimuon channel using 2011 CMS data
NASA Astrophysics Data System (ADS)
Silvers, David I.
The angular distributions of muons produced by the Drell-Yan process are measured as a function of dimuon transverse momentum in two ranges of rapidity. Events from pp collisions at sqrt( s) = 7 TeV were collected with the CMS detector using dimuon triggers and selected from data samples corresponding to 4.9 fb-1 of integrated luminosity. The two-dimensional angular distribution dN/dO of the negative muon in the Collins-Soper frame is fitted to determine the coefficients in a parametric form of the angular distribution. The measured coefficients are compared to next-to-leading order calculations. We observe that qq and leading order qg production dominate the Drell-Yan process at pT (mumu) <55 GeV/c, while higher-order qg production dominates the Drell-Yan process for 55< pT (mumu) <120 GeV/c.
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NASA Astrophysics Data System (ADS)
Atila, Metin; Katselis, George; Chumala, Paulos; Luo, Yu
2016-10-01
Phospholipids generally dominate in bacterial lipids. The negatively charged nature of phospholipids renders bacteria susceptible to cationic antibiotic peptides. In comparison with Gram-negative bacteria, Gram-positive bacteria in general have much less zwitterionic phosphatidylethanolamine. However, they are known for producing aminoacylated phosphatidylglycerol (PG), especially positively charged l-lysyl-PG, which is catalyzed by lysyl-PG synthase MprF, which appears to have a broad range of specificity for l-aminoacyl transfer RNAs. In addition, many Gram-positive bacteria also have a dlt-gene-coded d-alanylation pathway for lipoteichoic acids and wall teichoic acids covalently attached to a glycolipid or peptidoglycan. d-Alanylation also masks the dominant negative charge of the phosphate-rich polymers of teichoic acids. Using mass spectrometry, we have recently observed that precursor scans in negative mode for deprotonated amino acid fragments were most sensitive for ester-linked amino acids. Such a scan for precursors generating an m/ z 145 lysyl anion revealed lysyl-PG as well as an additional species 100 m/ z units greater than lysyl-PG. This unexpected species corresponded precisely to the expected mass of N-succinylated lysyl-PG. Tandem mass spectrometry revealed a precise match to the fragmentation pattern of this putative new species. PG, lysyl-PG, and N-succinyl-lysyl-PG may form a complete loop of charge reversal from -1 to +1 and then back to -1. Analogous charge reversal by N-succinylation of lysine residues in the bacterial as well as eukaryotic proteomes has been recently discovered as a major posttranslational modification. Such modification in bacterial lipids is possibly catalyzed by an enzyme homologous to the enzymes that modify lysine residues in proteins.
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Local dominance of exotic plants declines with residence time: a role for plant–soil feedback?
Speek, Tanja A.A.; Schaminée, Joop H.J.; Stam, Jeltje M.; Lotz, Lambertus A.P.; Ozinga, Wim A.; van der Putten, Wim H.
2015-01-01
Recent studies have shown that introduced exotic plant species may be released from their native soil-borne pathogens, but that they become exposed to increased soil pathogen activity in the new range when time since introduction increases. Other studies have shown that introduced exotic plant species become less dominant when time since introduction increases, and that plant abundance may be controlled by soil-borne pathogens; however, no study yet has tested whether these soil effects might explain the decline in dominance of exotic plant species following their initial invasiveness. Here we determine plant–soil feedback of 20 plant species that have been introduced into The Netherlands. We tested the hypotheses that (i) exotic plant species with a longer residence time have a more negative soil feedback and (ii) greater local dominance of the introduced exotic plant species correlates with less negative, or more positive, plant–soil feedback. Although the local dominance of exotic plant species decreased with time since introduction, there was no relationship of local dominance with plant–soil feedback. Plant–soil feedback also did not become more negative with increasing time since introduction. We discuss why our results may deviate from some earlier published studies and why plant–soil feedback may not in all cases, or not in all comparisons, explain patterns of local dominance of introduced exotic plant species. PMID:25770013
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Involvement of Clathrin-Mediated Endocytosis in Human Immunodeficiency Virus Type 1 Entry
Daecke, Jessica; Fackler, Oliver T.; Dittmar, Matthias T.; Kräusslich, Hans-Georg
2005-01-01
Productive entry of human immunodeficiency virus (HIV) is believed to occur by direct fusion at the plasma membrane. Endocytic uptake of HIV particles has been observed in several studies but is considered to be nonproductive, leading to virus degradation in the lysosome. We show here that endocytosis contributes significantly to productive HIV entry in HeLa cells by using trans dominant-negative mutants of dynamin and Eps15. Inducible expression of a dominant-negative mutant of dynamin in a CD4-positive HeLa cell line reduced HIV infection by 40 to 80%. This effect was independent of the infectious dose and was observed for three different isolates. Analysis of reverse transcription products by real-time PCR and of virus entry by delivery of a virion-associated Vpr-β-lactamase fusion protein revealed a similar reduction, indicating that the block occurred at the entry stage. A strong reduction of HIV entry was also observed upon transient transfection of a different trans dominant-negative variant of dynamin, and this reduction correlated with the relative inhibition of transferrin endocytosis. Expression of a dominant-negative variant of Eps15, which is specific for clathrin-dependent endocytosis, reduced HIV entry in HeLa cells by ca 95%, confirming the role of endocytosis for productive infection. In contrast, no effect was observed for a dominant-negative variant of caveolin. We conclude that dynamin-dependent, clathrin-mediated endocytosis can lead to productive entry of HIV in HeLa cells, suggesting this pathway as an alternative route of virus entry. PMID:15650184
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Positively charged particles in dusty plasmas.
Samarian, A A; Vaulina, O S; Nefedov, A P; Fortov, V E; James, B W; Petrov, O F
2001-11-01
The trapping of dust particles has been observed in a dc abnormal glow discharge dominated by electron attachment. A dust cloud of several tens of positively charged particles was found to form in the anode sheath region. An analysis of the experimental conditions revealed that these particles were positively charged due to emission process, in contrast to most other experiments on the levitation of dust particles in gas-discharge plasmas where negatively charged particles are found. An estimate of the particle charge, taking into account the processes of photoelectron and secondary electron emission from the particle surface, is in agreement with the experimental measured values.
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NIK and Cot cooperate to trigger NF-kappaB p65 phosphorylation.
Wittwer, Tobias; Schmitz, M Lienhard
2008-06-27
The serine/threonine kinase Cot triggers NF-kappaB-dependent transactivation and activation of various MAPKinases. Here we identify Cot as a novel p65 interacting protein kinase. Cot expression induces p65 phosphorylation at serines 536 and 468 in dependence from its kinase function. Accordingly, shRNA-mediated knockdown of Cot expression interferes with TNF-induced NF-kappaB-dependent gene expression. Also the C-terminally truncated, oncogenic form of Cot is able to trigger p65 phosphorylation. In vitro kinase assays and dominant negative mutants revealed that NIK functions downstream of Cot to mediate p65 phosphorylation.
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NASA Astrophysics Data System (ADS)
D'Hose, N.
2011-02-01
The study of exclusive reactions like Deeply Virtual Compton Scattering (DVCS) and Meson Production is one major part of the future COMPASS program in order to investigate nucleon structure through Generalised Parton Distributions (GPD). The high energy of the muon beam allows to measure the xB-dependence of the t-slope of the pure DVCS cross section and to study nucleon tomography. The use of positive and negative polarised muon beams allows to determine the Beam Charge and Spin Difference of the DVCS cross sections to access the real part of the Compton form factor related to the dominant GPD H.
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Lupton, S D; Brunton, L L; Kalberg, V A; Overell, R W
1991-06-01
The hygromycin phosphotransferase gene was fused in-frame with the herpes simplex virus type 1 thymidine kinase gene. The resulting fusion gene (termed HyTK) confers hygromycin B resistance for dominant positive selection and ganciclovir sensitivity for negative selection and provides a means by which these selectable phenotypes may be expressed and regulated as a single genetic entity.
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Dominant Negative Pleiotrophin Induces Tetraploidy and Aneuploidy in U87MG Human Glioblastoma Cells
Chang, Yunchao; Berenson, James R.; Wang, Zhaoyi; Deuel, Thomas F.
2007-01-01
Summary Pleiotrophin (PTN, Ptn) is an 18 kD secretory cytokine that is expressed in many human cancers, including glioblastoma. In previous experiments, interruption of the constitutive PTN signaling in human U87MG glioblastoma cells that inappropriately express endogenous Ptn reversed their rapid growth in vitro and their malignant phenotype in vivo. To seek a mechanism for the effect of the dominant negative PTN, flow cytometry was used to compare the profiles of U87MG cells and four clones of U87MG cells that express the dominant negative PTN (U87MG/PTN 1–40 cells); here, we report that the dominant negative PTN in U87MG cells induces tetraploidy and aneuploidy and arrests the tetraploid and aneuploid cells in the G1 phase of the cell cycle. The data suggest that PTN signaling may have a critical role in chromosomal segregation and cell cycle progression; the data suggest induction of tetraploidy and aneuploidy in U87MG glioblastoma cells may be an important mechanism that contributes to the loss of the malignant phenotype of U87MG cells. PMID:17067552
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Negative ion kinetics in RF glow discharges
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gottscho, R.A.; Gacbe, C.E.
1986-04-01
Using temporally and spatially resolved laser spectroscopy, the authors have determined the identities, approximate concentrations, effects on the local field, and kinetics of formation and loss of negative ions in RF discharges. CI/sup -/ and BCI/sub 3//sup -/ are the dominant negative ions found in low-frequency discharges through CI/sub 2/ and BCI/sub 3/, respectively. The electron affinity for CI is measured to be 3.6118 +- 0.0005 eV. Negative ion kinetics are strongly affected by application of the RF field. Formation of negative ions by attachment of slow electrons in RF discharges is governed by the extent and duration of electronmore » energy relaxation. Similarly, destruction of negative ions by collisional detachment and field extraction is dependent upon ion energy modulation. Thus, at low frequency, the anion density peaks at the beginning of the anodic and cathodic half-cycles after electrons have attached but before detachment and extraction have had time to occur. At higher frequencies, electrons have insufficient time to attach before they are reheated and the instantaneous anion density in the sheath is greatly reduced. When the negative ion density is comparable to the positive ion density, the plasma potential is observed to lie below the anode potential, double layers form between sheath and plasma, and anions and electrons are accelerated by large sheath fields to electrode surfaces.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hashimoto, Muneaki, E-mail: muneaki@juntendo.ac.jp; Nara, Takeshi, E-mail: tnara@juntendo.ac.jp; Enomoto, Masahiro, E-mail: menomoto@uhnres.utoronto.ca
Inositol 1,4,5-trisphosphate receptor (IP{sub 3}R) is a key regulator of intracellular Ca{sup 2+} concentration that release Ca{sup 2+} from Ca{sup 2+} stores in response to various external stimuli. IP{sub 3}R also works as a signal hub which form a platform for interacting with various proteins involved in diverse cell signaling. Previously, we have identified an IP{sub 3}R homolog in the parasitic protist, Trypanosoma cruzi (TcIP{sub 3}R). Parasites expressing reduced or increased levels of TcIP{sub 3}R displayed defects in growth, transformation, and infectivity. In the present study, we established parasitic strains expressing a dominant negative form of TcIP{sub 3}R, named DN-TcIP{submore » 3}R, to further investigate the physiological role(s) of TcIP{sub 3}R. We found that the growth of epimastigotes expressing DN-TcIP{sub 3}R was significantly slower than that of parasites with TcIP{sub 3}R expression levels that were approximately 65% of wild-type levels. The expression of DN-TcIP{sub 3}R in epimastigotes induced metacyclogenesis even in the normal growth medium. Furthermore, these epimastigotes showed the presence of dense mitochondria under a transmission electron microscope. Our findings confirm that TcIP{sub 3}R is crucial for epimastigote growth, as previously reported. They also suggest that a strong inhibition of the IP{sub 3}R-mediated signaling induces metacyclogenesis and that mitochondrial integrity is closely associated with this signaling. - Highlights: • We established T. cruzi strains expressing a dominant negative form of the TcIP{sub 3}R. • DN-TcIP{sub 3}R expression inhibits epimastigote growth and induces metacyclogenesis. • Microscopic analysis indicated TcIP{sub 3}R role in maintaining mitochondrial integrity. • Growth, but not microbial density, was altered by mammalian IP{sub 3}R inhibitor (2-APB).« less
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Wang, Shuyun; Huang, Qiaobing; Guo, Xiaohua; Brunk, Ulf T; Han, Jiahuai; Zhao, Keseng; Zhao, Ming
2010-08-01
Microvascular barrier damage, induced by thermal injury, imposes life-threatening problems owing to the pathophysiological consequences of plasma loss and impaired perfusion that finally may lead to multiple organ failure. The aim of the present study was to define the signaling role of selected mitogen-activated protein kinases (MAPKs) in general vessel hyperpermeability caused by burns and to look for a potential gene therapy. Rearrangement of cytoskeletons and cell tight junctions were evaluated by phalloidin labeling of actin and immunocytochemical demonstration of the ZO-1 protein, whereas blood vessel permeability was evaluated by a fluorescence ratio technique. The p38 MAPK inhibitor SB203580 largely blocked burn serum-induced stress-fiber formation and tight-junction damage. Using the adenoviral approach to transfect dominant negative forms of p38 MAPKs, we found that p38alpha and p38delta had similar effects. The in vivo part of the study showed that transfection of these two constructs significantly lowered general venular hyperpermeability and enhanced the survival of burned animals. Because the p38 MAPK pathway seems to play a crucial role in burn-induced vascular hyperpermeability, general transfection with p38 MAP dominant negative constructs might become a new therapeutic method to block burn-induced plasma leakage.
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Ferrer, Miriam; de Winter, Johan P; Mastenbroek, D C Jeroen; Curiel, David T; Gerritsen, Winald R; Giaccone, Giuseppe; Kruyt, Frank A E
2004-08-01
Fanconi anemia (FA) is a rare genetic disorder characterized by bone-marrow failure and cellular hypersensitivity to crosslinking agents, including cisplatin. Here, we studied the use of the FA pathway as a possible target for cancer gene therapy with the aim to sensitize tumor cells for cisplatin by interfering with the FA pathway. As proof-of-principle, FA and non-FA lymphoblast-derived tumors were grown subcutaneously in scid mice and treated with two different concentrations of cisplatin. As predicted, the antitumor response was considerably improved in FA tumors. An adenoviral vector encoding a dominant-negative form of FANCA, FANCA600DN, was generated that interfered with endogenous FANCA-FANCG interaction resulting in the disruption of the FA pathway as illustrated by disturbed FANCD2 monoubiquitination. A panel of cell lines, including non-small-cell lung cancer cells, could be sensitized approximately two- to three-fold for cisplatin after Ad.CMV.FANCA600DN infection that may increase upon enhanced infection efficiency. In conclusion, targeting the FA pathway may provide a novel strategy for the sensitization of solid tumors for cisplatin and, in addition, provides a tool for examining the role of the FA pathway in determining chemoresistance in different tumor types.
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Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy.
Luo, Ji; McMullen, Julie R; Sobkiw, Cassandra L; Zhang, Li; Dorfman, Adam L; Sherwood, Megan C; Logsdon, M Nicole; Horner, James W; DePinho, Ronald A; Izumo, Seigo; Cantley, Lewis C
2005-11-01
Class I(A) phosphoinositide 3-kinases (PI3Ks) are activated by growth factor receptors, and they regulate, among other processes, cell growth and organ size. Studies using transgenic mice overexpressing constitutively active and dominant negative forms of the p110alpha catalytic subunit of class I(A) PI3K have implicated the role of this enzyme in regulating heart size and physiological cardiac hypertrophy. To further understand the role of class I(A) PI3K in controlling heart growth and to circumvent potential complications from the overexpression of dominant negative and constitutively active proteins, we generated mice with muscle-specific deletion of the p85alpha regulatory subunit and germ line deletion of the p85beta regulatory subunit of class I(A) PI3K. Here we show that mice with cardiac deletion of both p85 subunits exhibit attenuated Akt signaling in the heart, reduced heart size, and altered cardiac gene expression. Furthermore, exercise-induced cardiac hypertrophy is also attenuated in the p85 knockout hearts. Despite such defects in postnatal developmental growth and physiological hypertrophy, the p85 knockout hearts exhibit normal contractility and myocardial histology. Our results therefore provide strong genetic evidence that class I(A) PI3Ks are critical regulators for the developmental growth and physiological hypertrophy of the heart.
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Jully, Babu; Vijayalakshmi, Ramshankar; Gopal, Gopisetty; Sabitha, Kesavan; Rajkumar, Thangarajan
2012-11-12
Ewing's sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor. In the present study, we have further characterized the junction region of the EWS-FLI1 fusion protein. In-silico model of EWS-FLI1 fusion protein was analysed for ligand binding sites, and a putative region (amino acid (aa) 251-343 of the type 1 fusion protein) in the vicinity of the fusion junction was cloned and expressed using bacterial expression. The recombinant protein was characterized by Circular Dichroism (CD). We then expressed aa 251-280 ectopically in Ewing's sarcoma cell-line and its effect on cell proliferation, tumorigenicity and expression of EWS-FLI1 target genes were analysed. Our modelling analysis indicated that Junction region (aa 251-343) encompasses potential ligand biding sites in the EWS-FLI1 protein and when expressed in bacteria was present as soluble form. Ectopically expressing this region in Ewing's sarcoma cells inhibited tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative biological effect. Junction region can be exploited further as target for drug development in future to specifically target EWS-FLI1 in Ewing's Sarcoma.
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Gabor, K A; Charette, J R; Pietraszewski, M J; Wingfield, D J; Shim, J S; Millard, P J; Kim, C H
2015-08-01
Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Molday, Robert S; Molday, Laurie L; Loewen, Christopher J R
2004-01-01
Peripherin 2 is a photoreceptor-specific membrane protein implicated in outer segment disk morphogenesis and linked to various retinopathies including autosomal dominant retinitis pigmentosa (ADRP). Peripherin 2 and ROM1 assemble as a mixture of core noncovalent homomeric and heteromeric tetramers that further link together through disulfide bonds to form higher order oligomers. These complexes are critical for disk rim formation and outer segment structure through interaction with the cGMP-gated channel and other photoreceptor proteins. We have examined the role of subunit assembly in peripherin 2 targeting to disks, outer segment structure, and photoreceptor degeneration by examining molecular and cellular properties of peripherin 2 mutants in COS-1 cells and transgenic Xenopus laevis rod photoreceptors. Wild-type (WT) and the ADRP-linked P216L mutant were transported and incorporated into newly formed outer segment disks of transgenic X. laevis. The P216L mutant, however, induced progressive outer segment instability and photoreceptor degeneration possibly through the introduction of a new N-linked oligosaccharide chain. In contrast, the C214S and L185P disease-linked, tetramerization-defective mutants, were retained in the inner segment, but did not affect outer segment structure or induce photoreceptor degeneration. Together, these results indicate that peripherin 2 mutations can cause ADRP either through a deficiency in WT peripherin 2 (C214S, 1.185P) or by a dominant negative effect on disk stability (P216L).
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NASA Astrophysics Data System (ADS)
Ivanov, Konstantin; Pinchuk, Irina; Gorodnichev, Roman; Polyanskaya, Lubov
2016-04-01
Methods establishment of soil microbial cells size estimation called from the importance of current needs of research in microbial ecology. Some of the methods need to be improved for more detailed view of changes happen in microbiome of terrestrial ecosystems. The combination of traditional microscopy methods, fluorescence and filtration in addition to cutting-edge DNA analysis gives a wide range of the approaches for soil microbial ecologists in their research questions. In the most of the cases the bacterial cells size is limited of the natural conditions such as lack of nutrients or stress factors due to heterogeneity of soil system. In the samples of soils, lakes and rivers sediments, snow and rain water the bacterial cells were detected minimally of 0.2 microns. We established the combination of the cascade filtration and fluorescent microscopy for complex analysis of different terrestrial ecosystems and various soil types. Our modification based on the use of successively filtered soil suspension for collection of microbes by the membrane pores decrease. Combination with fluorescence microscopy and DNA analysis via FISH method gave the presentation of microbial interactions and review of ecological strategies of soil microorganisms. Humus horizons of primitive arctic soil were the most favorable for bacterial growth. Quantified biomass of soil bacteria depends on the dominance of cells with specific dimensions caused of stress factors. The average bacterial size of different soil varied from 0.23 to 0.38 microns, however in humus horizons of arctic soil we detected the contrast dominance of the bigger bacterial cells sized of 1.85 microns. Fungi in this case contributed to increase the availability of organic matter for bacteria because the fungal mycelium forms the appreciable part of microbial biomass of primitive arctic soil. The dominant content of bigger bacterial cells in forest and fallow soil as well as the opposite situation in arable soils caused by the availability of nutrients (glucose) and the degree of agricultural anthropogenic stress. Various combinations of factors such as stressful conditions (anaerobiosis, acidity and temperature) influenced on bacterial size. The decrease of these stress factors resulted in return to the original bacterial cell size in soil. Furthermore the modification of gram-negative bacteria quantification was performed and combined with FISH method and DNA extraction. We established the methodological comparison of gram-negative bacteria groups in aerobic and anaerobic conditions. Due to absence of significant difference between the most frequent soil gram-negative bacteria groups we concluded the important ecological role of gram-negative bacteria as common group of microorganisms in natural polymer degradation. Depending on nutrient (glucose, cellulose, chitin) gram-negative bacteria competed with actinomyces for available nutrients at the different time, what explained by the ecological flexibility of this soil bacteria group. The experiments showed expressed faster chitinolytic activity of soil gram-negative bacteria compare to actinomyces. Thus our approaches to use the combination both traditional and cutting-edge methods, forms the unique basement for various research and mostly open the wide doors to design new scientific experiments in ecology of terrestrial ecosystems and especially in soil microbial ecology.
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Tara L. Keyser
2012-01-01
Growth dominance provides a quantitative description of the relative contribution of individual trees to stand growth. Positive dominance occurs when the largest individuals account for a greater proportion of growth period increment than total biomass. Conversely, negative dominance occurs when the smallest trees account for a greater proportion of the growth period...
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C-terminal oligomerization of podocin mediates interallelic interactions.
Stráner, Pál; Balogh, Eszter; Schay, Gusztáv; Arrondel, Christelle; Mikó, Ágnes; L'Auné, Gerda; Benmerah, Alexandre; Perczel, András; K Menyhárd, Dóra; Antignac, Corinne; Mollet, Géraldine; Tory, Kálmán
2018-07-01
Interallelic interactions of membrane proteins are not taken into account while evaluating the pathogenicity of sequence variants in autosomal recessive disorders. Podocin, a membrane-anchored component of the slit diaphragm, is encoded by NPHS2, the major gene mutated in hereditary podocytopathies. We formerly showed that its R229Q variant is only pathogenic when trans-associated to specific 3' mutations and suggested the causal role of an abnormal C-terminal dimerization. Here we show by FRET analysis and size exclusion chromatography that podocin oligomerization occurs exclusively through the C-terminal tail (residues 283-382): principally through the first C-terminal helical region (H1, 283-313), which forms a coiled coil as shown by circular dichroism spectroscopy, and through the 332-348 region. We show the principal role of the oligomerization sites in mediating interallelic interactions: while the monomer-forming R286Tfs*17 podocin remains membranous irrespective of the coexpressed podocin variant identity, podocin variants with an intact H1 significantly influence each other's localization (r 2 = 0.68, P = 9.2 × 10 -32 ). The dominant negative effect resulting in intracellular retention of the pathogenic F344Lfs*4-R229Q heterooligomer occurs in parallel with a reduction in the FRET efficiency, suggesting the causal role of a conformational rearrangement. On the other hand, oligomerization can also promote the membrane localization: it can prevent the endocytosis of F344Lfs*4 or F344* podocin mutants induced by C-terminal truncation. In conclusion, C-terminal oligomerization of podocin can mediate both a dominant negative effect and interallelic complementation. Interallelic interactions of NPHS2 are not restricted to the R229Q variant and have to be considered in compound heterozygous individuals. Copyright © 2018 Elsevier B.V. All rights reserved.
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Fitzgerald, Kerry D; Semler, Bert L
2013-09-01
Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. Copyright © 2013 Elsevier B.V. All rights reserved.
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Michalopoulos, Ioannis; Sideridou, Maria; Tsimaratou, Katerina; Christodoulou, Ioannis; Pyrillou, Katerina; Gorgoulis, Vassilis; Vlahopoulos, Spiros; Zoumpourlis, Vassilis
2012-01-01
Estrogen receptors (ER), namely ERα and ERβ, are hormone-activated transcription factors with an important role in carcinogenesis. In the present study, we aimed at elucidating the implication of ERα in skin cancer, using chemically-induced mouse skin tumours, as well as cell lines representing distinct stages of mouse skin oncogenesis. First, using immunohistochemical staining we showed that ERα is markedly increased in aggressive mouse skin tumours in vivo as compared to the papilloma tumours, whereas ERβ levels are low and become even lower in the aggressive spindle tumours of carcinogen-treated mice. Then, using the multistage mouse skin carcinogenesis model, we showed that ERα gradually increases during promotion and progression stages of mouse skin carcinogenesis, peaking at the most aggressive stage, whereas ERβ levels only slightly change throughout skin carcinogenesis. Stable transfection of the aggressive, spindle CarB cells with a dominant negative form of ERα (dnERα) resulted in reduced ERα levels and reduced binding to estrogen responsive elements (ERE)-containing sequences. We characterized two highly conserved EREs on the mouse ERα promoter through which dnERα decreased endogenous ERα levels. The dnERα-transfected CarB cells presented altered protein levels of cytoskeletal and cell adhesion molecules, slower growth rate and impaired anchorage-independent growth in vitro, whereas they gave smaller tumours with extended latency period of tumour onset in vivo. Our findings suggest an implication of ERα in the aggressiveness of spindle mouse skin cancer cells, possibly through regulation of genes affecting cell shape and adhesion, and they also provide hints for the effective targeting of spindle cancer cells by dnERα. PMID:22870269
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Insulin stimulates the expression of the SHARP-1 gene via multiple signaling pathways.
Takagi, K; Asano, K; Haneishi, A; Ono, M; Komatsu, Y; Yamamoto, T; Tanaka, T; Ueno, H; Ogawa, W; Tomita, K; Noguchi, T; Yamada, K
2014-06-01
The rat enhancer of split- and hairy-related protein-1 (SHARP-1) is a basic helix-loop-helix transcription factor. An issue of whether SHARP-1 is an insulin-inducible transcription factor was examined. Insulin rapidly increased the level of SHARP-1 mRNA both in vivo and in vitro. Then, signaling pathways involved with the increase of SHARP-1 mRNA by insulin were determined in H4IIE rat hepatoma cells. Pretreatments with LY294002, wortmannin, and staurosporine completely blocked the induction effect, suggesting the involvement of both phosphoinositide 3-kinase (PI 3-K) and protein kinase C (PKC) pathways. In fact, overexpression of a dominant negative form of atypical protein kinase C lambda (aPKCλ) significantly decreased the induction of the SHARP-1 mRNA. In addition, inhibitors for the small GTPase Rac or Jun N-terminal kinase (JNK) also blocked the induction of SHARP-1 mRNA by insulin. Overexpression of a dominant negative form of Rac1 prevented the activation by insulin. Furthermore, actinomycin D and cycloheximide completely blocked the induction of SHARP-1 mRNA by insulin. Finally, when a SHARP-1 expression plasmid was transiently transfected with various reporter plasmids into H4IIE cells, the promoter activity of PEPCK reporter plasmid was specifically decreased. Thus, we conclude that insulin induces the SHARP-1 gene expression at the transcription level via a both PI 3-K/aPKCλ/JNK- and a PI 3-K/Rac/JNK-signaling pathway; protein synthesis is required for this induction; and that SHARP-1 is a potential repressor of the PEPCK gene expression. © Georg Thieme Verlag KG Stuttgart · New York.
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Carprofen Induction of p75NTR Dependent Apoptosis via the p38 MAPK Pathway in Prostate Cancer Cells
Khwaja, Fatima S.; Quann, Emily J.; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel
2008-01-01
The p75NTR functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we demonstrated that treatment with R-flurbiprofen or ibuprofen induced p75NTR expression in several prostate cancer cell lines leading to p75NTR mediated decreased survival. Utilizing the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico data base of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75NTR levels and inhibition of cell survival. Prostate (PC-3, DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75NTR associated loss of survival than breast (MCF7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant negative form of p75NTR prior to carprofen treatment partially rescued cell survival demonstrating a cause and effect relationship between carprofen induction of p75NTR levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF7 and 3T3 cells. Furthermore, siRNA knockdown of the p38 MAPK protein prevented induction of p75NTR by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 minute. Expression of a dominant negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75NTR protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75NTR dependent apoptosis via the p38 MAPK pathway in prostate cancer cells. PMID:18974393
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Lo, Ting Ling; Yusoff, Permeen; Fong, Chee Wai; Guo, Ke; McCaw, Ben J; Phillips, Wayne A; Yang, He; Wong, Esther Sook Miin; Leong, Hwei Fen; Zeng, Qi; Putti, Thomas Choudary; Guy, Graeme R
2004-09-01
Sprouty (Spry) proteins were found to be endogenous inhibitors of the Ras/mitogen-activated protein kinase pathway that play an important role in the remodeling of branching tissues. We investigated Spry expression levels in various cancers and found that Spry1 and Spry2 were down-regulated consistently in breast cancers. Such prevalent patterns of down-regulation may herald the later application of these isoforms as tumor markers that are breast cancer specific and more profound than currently characterized markers. Spry1 and 2 were expressed specifically in the luminal epithelial cells of breast ducts, with higher expression during stages of tissue remodeling when the epithelial ducts are forming and branching. These findings suggest that Sprys might be involved as a modeling counterbalance and surveillance against inappropriate epithelial expansion. The abrogation of endogenous Spry activity in MCF-7 cells by the overexpression of a previously characterized dominant-negative mutant of Spry, hSpry2Y55F resulted in enhanced cell proliferation in vitro. The hSpry2Y55F stably expressing cells also formed larger and greater number of colonies in the soft-agar assay. An in vivo nude mice assay showed a dramatic increase in the tumorigenic potential of hSpry2Y55F stable cells. The consistent down-regulation of Spry1 and 2 in breast cancer and the experimental evidence using a dominant-negative hSpry2Y55F indicate that Spry proteins may actively maintain tissue integrity that runs amok when their expression is decreased below normal threshold levels. This alludes to a previously unrecognized role for Sprys in cancer development.
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Warner, Timothy A.; Shen, Wangzhen; Huang, Xuan; Liu, Zhong; Macdonald, Robert L.; Kang, Jing-Qiong
2016-01-01
Genetic epilepsy is a common disorder with phenotypic variation, but the basis for the variation is unknown. Comparing the molecular pathophysiology of mutations in the same epilepsy gene may provide mechanistic insights into the phenotypic heterogeneity. GABRG2 is an established epilepsy gene, and mutations in it produce epilepsy syndromes with varying severities. The disease phenotype in some cases may be caused by simple loss of subunit function (functional haploinsufficiency), while others may be caused by loss-of-function plus dominant negative suppression and other cellular toxicity. Detailed molecular defects and the corresponding seizures and related comorbidities resulting from haploinsufficiency and dominant negative mutations, however, have not been compared. Here we compared two mouse models of GABRG2 loss-of-function mutations associated with epilepsy with different severities, Gabrg2+/Q390X knockin (KI) and Gabrg2+/- knockout (KO) mice. Heterozygous Gabrg2+/Q390XKI mice are associated with a severe epileptic encephalopathy due to a dominant negative effect of the mutation, while heterozygous Gabrg2+/- KO mice are associated with mild absence epilepsy due to simple haploinsufficiency. Unchanged at the transcriptional level, KI mice with severe epilepsy had neuronal accumulation of mutant γ2 subunits, reduced remaining functional wild-type subunits in dendrites and synapses, while KO mice with mild epilepsy had no intracellular accumulation of the mutant subunits and unaffected biogenesis of the remaining wild-type subunits. Consequently, KI mice with dominant negative mutations had much less wild-type receptor expression, more severe seizures and behavioural comorbidities than KO mice. This work provides insights into the pathophysiology of epilepsy syndrome heterogeneity and designing mechanism-based therapies. PMID:27340224
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NASA Astrophysics Data System (ADS)
Su, Wan-Ching; Chang, Ting-Chang; Liao, Po-Yung; Chen, Yu-Jia; Chen, Bo-Wei; Hsieh, Tien-Yu; Yang, Chung-I.; Huang, Yen-Yu; Chang, Hsi-Ming; Chiang, Shin-Chuan; Chang, Kuan-Chang; Tsai, Tsung-Ming
2017-03-01
This paper investigates the degradation behavior of InGaZnO thin film transistors (TFTs) under negative bias illumination stress (NBIS). TFT devices with two different source and drain layouts were exanimated: one having a parallel format electrode and the other with UI format electrode. UI means that source/drain electrodes shapes is defined as a forked-shaped structure. The I-V curve of the parallel electrode exhibited a symmetric degradation under forward and reverse sweeping in the saturation region after 1000 s NBIS. In contrast, the I-V curve of the UI electrode structure under similar conditions was asymmetric. The UI electrode structure also shows a stretch-out phenomenon in its C-V measurement. Finally, this work utilizes the ISE-Technology Computer Aided Design (ISE-TCAD) system simulations, which simulate the electron field and IV curves, to analyze the mechanisms dominating the parallel and UI device degradation behaviors.
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NASA Astrophysics Data System (ADS)
Kaya, Ismet I.
2007-03-01
A ballistic conductor is restricted to have positive three terminal resistance just as a Drude conductor. Intercarrier scattering does not influence the conductivity of the latter transport regime and does not exist in the former. However, as the electron energies increased, in the intermediate regime, single or few intercarrier scattering events starts to dominate the transport properties of a conductor with sufficiently small dimensions. A three-terminal device formed by two electrostatic barriers crossing an asymmetrically patterned two dimensional electron gas displays an unusual potential depression at the middle contact, yielding absolute negative resistance. The device displays momentum and current transfer ratios that far exceed unity. The observed reversal of the current or potential in the middle terminal is interpreted as the analog of Bernoulli's effect in a Fermi liquid. The results are explained by directional scattering of electrons in two dimensions.
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Left-hand dominance in children: Prevalence and maternal stereotypes in a South-east Nigerian city.
Uwaezuoke, Samuel N; Eke, Christopher B; Nwobi, Emmanuel A
2015-01-01
The objectives of the study are to estimate the prevalence of left-hand dominance among children of selected mothers in an urban city and to determine the mothers' stereotypes about left-handedness. A cross-sectional study of mothers (N = 222) selected by systematic random sampling was done. The mothers were interviewed with structured questionnaires. Data were analyzed with appropriate descriptive statistics on SPSS. The estimated prevalence of left-hand dominance in their children was 7.52%. A left-handed mother was more likely to have a left-handed child. A substantial number of the mothers held negative stereotypes about left-hand dominance and showed a good knowledge about other types of handedness with a significant difference in the responses between right-handers and left-handers. The prevalence of left-hand dominance in their children supports previous reports which show that left-handedness usually occurs in less than 10% of the population. The mothers' negative stereotypes signify the likelihood of stigmatizing the children with this hand dominance.
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NASA Astrophysics Data System (ADS)
Sanger, Demas S.; Haneishi, Hideaki; Miyake, Yoichi
1995-08-01
This paper proposed a simple and automatic method for recognizing the light sources from various color negative film brands by means of digital image processing. First, we stretched the image obtained from a negative based on the standardized scaling factors, then extracted the dominant color component among red, green, and blue components of the stretched image. The dominant color component became the discriminator for the recognition. The experimental results verified that any one of the three techniques could recognize the light source from negatives of any film brands and all brands greater than 93.2 and 96.6% correct recognitions, respectively. This method is significant for the automation of color quality control in color reproduction from color negative film in mass processing and printing machine.
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Soylu Yalcinkaya, Nur; Estrada-Villalta, Sara; Adams, Glenn
2017-01-01
Most research links (racial) essentialism to negative intergroup outcomes. We propose that this conclusion reflects both a narrow conceptual focus on biological/genetic essence and a narrow research focus from the perspective of racially dominant groups. We distinguished between beliefs in biological and cultural essences, and we investigated the implications of this distinction for support of social justice policies (e.g., affirmative action) among people with dominant (White) and subordinated (e.g., Black, Latino) racial identities in the United States. Whereas, endorsement of biological essentialism may have similarly negative implications for social justice policies across racial categories, we investigated the hypothesis that endorsement of cultural essentialism would have different implications across racial categories. In Studies 1a and 1b, we assessed the properties of a cultural essentialism measure we developed using two samples with different racial/ethnic compositions. In Study 2, we collected data from 170 participants using an online questionnaire to test the implications of essentialist beliefs for policy support. Consistent with previous research, we found that belief in biological essentialism was negatively related to policy support for participants from both dominant and subordinated categories. In contrast, the relationship between cultural essentialism and policy support varied across identity categories in the hypothesized way: negative for participants from the dominant category but positive for participants from subordinated categories. Results suggest that cultural essentialism may provide a way of identification that subordinated communities use to mobilize support for social justice. PMID:28611723
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Calcium-Mediated Apoptosis and Apoptotic Sensitization in Prostate Cancer
2003-06-01
tyrosine phosphatase, PTP1B . To study their direct involvement in apoptosis and signaling, PC cells were transfected with dominant negative caspase 7...and inducible constructs of activated PTP1B B. Dominant negative caspase 7 suppressed activation of endogenous caspase 7 by calcium ionophore...supporting a role for its recruitment into the calcium initiated apoptotic process. Activated PTP1B expression (but not a phosphatase-dead mutant
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Fanzani, Alessandro; Stoppani, Elena; Gualandi, Laura; Giuliani, Roberta; Galbiati, Ferruccio; Rossi, Stefania; Fra, Anna; Preti, Augusto; Marchesini, Sergio
2007-10-30
Caveolin-3 (Cav-3) is the main scaffolding protein present in myofiber caveolae. We transfected C2C12 myoblasts with dominant negative forms of Cav-3, P104L or DeltaTFT, respectively, which cause the limb-girdle muscular dystrophy 1-C. Both these forms triggered Cav-3 loss during C2C12 cell differentiation. The P104L mutation reduced myofiber formation by impaired AKT signalling, accompanied by dramatic expression of the E3 ubiquitin ligase Atrogin. On the other hand, the DeltaTFT mutation triggered hypertrophic myotubes sustained by prolonged AKT activation, but independent of increased levels of follistatin and interleukin 4 expression. These data suggest that separated mutations within the same dystrophy-related gene may cause muscle degeneration through different mechanisms.
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Bulleri, Fabio; Couraudon-Réale, Marine; Lison de Loma, Thierry; Claudet, Joachim
2013-01-01
Shifts in dominance from corals to macroalgae are occurring in many coral reefs worldwide. Macroalgal canopies, while competing for space with coral colonies, may also form a barrier to herbivorous and corallivorous fish, offering protection to corals. Thus, corals could either suffer from enhanced competition with canopy-forming and understorey macroalgae or benefit from predator exclusion. Here, we tested the hypothesis that the effects of the brown, canopy-forming macroalga, Turbinaria ornata, on the survival and growth of corals can vary according to its cover, to the presence or absence of herbivorous and corallivorous fish and to the morphological types of corals. Over a period of 66 days, two coral species differing in growth form, Acropora pulchra and Porites rus, were exposed to three different covers of T. ornata (absent versus medium versus high), in the presence or absence of fish. Irrespective of the cover of T. ornata, fish exclusion reduced mortality rates of A. pulchra. Following fish exclusion, a high cover of T. ornata depressed the growth of this branched coral, whilst it had no effect when fish species were present. P. rus suffered no damage from corallivorous fish, but its growth was decreased by high covers of T. ornata, irrespective of the presence or absence of fish. These results show that negative effects of T. ornata on some coral species are subordinate to those of fish predation and are, therefore, likely to manifest only on reefs severely depleted of predators. In contrast, space dominance by T. ornata may decrease the growth of other coral species regardless of predation intensity. In general, this study shows that susceptibility to predation may determine the severity of the effects of canopy-forming macroalgae on coral growth.
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NASA Technical Reports Server (NTRS)
Rejmankova, E.; Pope, K. O.; Roberts, D. R.; Lege, M. G.; Andre, R.; Greico, J.; Alonzo, Y.
1998-01-01
Surveys of larval habitats of Anopheles vestitipennis and Anopheles punctimacula were conducted in Belize, Central America. Habitat analysis and classification resulted in delineation of eight habitat types defined by dominant life forms and hydrology. Percent cover of tall dense macrophytes, shrubs, open water, and pH were significantly different between sites with and without An. vestitipennis. For An. punctimacula, percent cover of tall dense macrophytes, trees, detritus, open water, and water depth were significantly different between larvae positive and negative sites. The discriminant function for An. vestitipennis correctly predicted the presence of larvae in 65% of sites and correctly predicted the absence of larvae in 88% of sites. The discriminant function for An. punctimacula correctly predicted 81% of sites for the presence of larvae and 45% for the absence of larvae. Canonical discriminant analysis of the three groups of habitats (An. vestitipennis positive; An. punctimacula positive; all negative) confirmed that while larval habitats of An. punctimacula are clustered in the tree dominated area, larval habitats of An. vestitipennis were found in both tree dominated and tall dense macrophyte dominated environments. The forest larval habitats of An. vestitipennis and An. punctimacula seem to be randomly distributed among different forest types. Both species tend to occur in denser forests with more detritus, shallower water, and slightly higher pH. Classification of dry season (February) SPOT multispectral satellite imagery produced 10 land cover types with the swamp forest and tall dense marsh classes being of particular interest. The accuracy assessment showed that commission errors for the tall, dense marsh and swamp forest appeared to be minor; but omission errors were significant, especially for the swamp forest (perhaps because no swamp forests are flooded in February). This means that where the classification indicates there are An. vestitipennis breeding sites, they probably do exist; but breeding sites in many locations are not identified and could be more abundant than indicated.
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Embodiment of abstract concepts: good and bad in right- and left-handers.
Casasanto, Daniel
2009-08-01
Do people with different kinds of bodies think differently? According to the body-specificity hypothesis, people who interact with their physical environments in systematically different ways should form correspondingly different mental representations. In a test of this hypothesis, 5 experiments investigated links between handedness and the mental representation of abstract concepts with positive or negative valence (e.g., honesty, sadness, intelligence). Mappings from spatial location to emotional valence differed between right- and left-handed participants. Right-handers tended to associate rightward space with positive ideas and leftward space with negative ideas, but left-handers showed the opposite pattern, associating rightward space with negative ideas and leftward with positive ideas. These contrasting mental metaphors for valence cannot be attributed to linguistic experience, because idioms in English associate good with right but not with left. Rather, right- and left-handers implicitly associated positive valence more strongly with the side of space on which they could act more fluently with their dominant hands. These results support the body-specificity hypothesis and provide evidence for the perceptuomotor basis of even the most abstract ideas.
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Shinkuma, Satoru; Guo, Zongyou; Christiano, Angela M
2016-05-17
Genome editing with engineered site-specific endonucleases involves nonhomologous end-joining, leading to reading frame disruption. The approach is applicable to dominant negative disorders, which can be treated simply by knocking out the mutant allele, while leaving the normal allele intact. We applied this strategy to dominant dystrophic epidermolysis bullosa (DDEB), which is caused by a dominant negative mutation in the COL7A1 gene encoding type VII collagen (COL7). We performed genome editing with TALENs and CRISPR/Cas9 targeting the mutation, c.8068_8084delinsGA. We then cotransfected Cas9 and guide RNA expression vectors expressed with GFP and DsRed, respectively, into induced pluripotent stem cells (iPSCs) generated from DDEB fibroblasts. After sorting, 90% of the iPSCs were edited, and we selected four gene-edited iPSC lines for further study. These iPSCs were differentiated into keratinocytes and fibroblasts secreting COL7. RT-PCR and Western blot analyses revealed gene-edited COL7 with frameshift mutations degraded at the protein level. In addition, we confirmed that the gene-edited truncated COL7 could neither associate with normal COL7 nor undergo triple helix formation. Our data establish the feasibility of mutation site-specific genome editing in dominant negative disorders.
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A Novel Method to Screen for Dominant Negative ATM Mutations in Familial Breast Cancer
2005-04-01
carry dominant negative mutation in ATM due to natural variation amongst LCLs. Microarrays have been performed to determine differences in gene expression... genes that are altered in their expression in ATMmutation carriers. The validation of this data in carriers of different ATM mutation indicated that the...heterozygous carriers of T727 1 G mutation display a gene expression phenotype that appears identical to carriers of protein truncating mutations in
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Surface charge effects in protein adsorption on nanodiamonds
NASA Astrophysics Data System (ADS)
Aramesh, M.; Shimoni, O.; Ostrikov, K.; Prawer, S.; Cervenka, J.
2015-03-01
Understanding the interaction of proteins with charged diamond nanoparticles is of fundamental importance for diverse biomedical applications. Here we present a thorough study of protein binding, adsorption kinetics and structure on strongly positively (hydrogen-terminated) and negatively (oxygen-terminated) charged nanodiamond particles using a quartz crystal microbalance by dissipation and infrared spectroscopy. By using two model proteins (bovine serum albumin and lysozyme) of different properties (charge, molecular weight and rigidity), the main driving mechanism responsible for the protein binding to the charged nanoparticles was identified. Electrostatic interactions were found to dominate the protein adsorption dynamics, attachment and conformation. We developed a simple electrostatic model that can qualitatively explain the observed adsorption behaviour based on charge-induced pH modifications near the charged nanoparticle surfaces. Under neutral conditions, the local pH around the positively and negatively charged nanodiamonds becomes very high (11-12) and low (1-3) respectively, which has a profound impact on the protein charge, hydration and affinity to the nanodiamonds. Small proteins (lysozyme) were found to form multilayers with significant conformational changes to screen the surface charge, while larger proteins (albumin) formed monolayers with minor conformational changes. The findings of this study provide a step forward toward understanding and eventually predicting nanoparticle interactions with biofluids.Understanding the interaction of proteins with charged diamond nanoparticles is of fundamental importance for diverse biomedical applications. Here we present a thorough study of protein binding, adsorption kinetics and structure on strongly positively (hydrogen-terminated) and negatively (oxygen-terminated) charged nanodiamond particles using a quartz crystal microbalance by dissipation and infrared spectroscopy. By using two model proteins (bovine serum albumin and lysozyme) of different properties (charge, molecular weight and rigidity), the main driving mechanism responsible for the protein binding to the charged nanoparticles was identified. Electrostatic interactions were found to dominate the protein adsorption dynamics, attachment and conformation. We developed a simple electrostatic model that can qualitatively explain the observed adsorption behaviour based on charge-induced pH modifications near the charged nanoparticle surfaces. Under neutral conditions, the local pH around the positively and negatively charged nanodiamonds becomes very high (11-12) and low (1-3) respectively, which has a profound impact on the protein charge, hydration and affinity to the nanodiamonds. Small proteins (lysozyme) were found to form multilayers with significant conformational changes to screen the surface charge, while larger proteins (albumin) formed monolayers with minor conformational changes. The findings of this study provide a step forward toward understanding and eventually predicting nanoparticle interactions with biofluids. Electronic supplementary information (ESI) available: The FTIR spectrum of nanodiamonds, QCM-D profiles of 50 nm nanodiamond adsorption on silica surfaces, QCM-D profiles of protein desorption after rinsing with water (rinsing experiment) and the full FTIR spectrum of proteins before and after adsorption on ND particles. See DOI: 10.1039/c5nr00250h
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Strain, Elisabeth M A; Thomson, Russell J; Micheli, Fiorenza; Mancuso, Francesco P; Airoldi, Laura
2014-11-01
Identifying the type and strength of interactions between local anthropogenic and other stressors can help to set achievable management targets for degraded marine ecosystems and support their resilience by identifying local actions. We undertook a meta-analysis, using data from 118 studies to test the hypothesis that ongoing global declines in the dominant habitat along temperate rocky coastlines, forests of canopy-forming algae and/or their replacement by mat-forming algae are driven by the nonadditive interactions between local anthropogenic stressors that can be addressed through management actions (fishing, heavy metal pollution, nutrient enrichment and high sediment loads) and other stressors (presence of competitors or grazers, removal of canopy algae, limiting or excessive light, low or high salinity, increasing temperature, high wave exposure and high UV or CO2 ), not as easily amenable to management actions. In general, the cumulative effects of local anthropogenic and other stressors had negative effects on the growth and survival of canopy-forming algae. Conversely, the growth or survival of mat-forming algae was either unaffected or significantly enhanced by the same pairs of stressors. Contrary to our predictions, the majority of interactions between stressors were additive. There were however synergistic interactions between nutrient enrichment and heavy metals, the presence of competitors, low light and increasing temperature, leading to amplified negative effects on canopy-forming algae. There were also synergistic interactions between nutrient enrichment and increasing CO2 and temperature leading to amplified positive effects on mat-forming algae. Our review of the current literature shows that management of nutrient levels, rather than fishing, heavy metal pollution or high sediment loads, would provide the greatest opportunity for preventing the shift from canopy to mat-forming algae, particularly in enclosed bays or estuaries because of the higher prevalence of synergistic interactions between nutrient enrichment with other local and global stressors, and as such it should be prioritized. © 2014 John Wiley & Sons Ltd.
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First- and second-language phonological representations in the mental lexicon.
Sebastian-Gallés, Núria; Rodríguez-Fornells, Antoni; de Diego-Balaguer, Ruth; Díaz, Begoña
2006-08-01
Performance-based studies on the psychological nature of linguistic competence can conceal significant differences in the brain processes that underlie native versus nonnative knowledge of language. Here we report results from the brain activity of very proficient early bilinguals making a lexical decision task that illustrates this point. Two groups of Spanish-Catalan early bilinguals (Spanish-dominant and Catalan-dominant) were asked to decide whether a given form was a Catalan word or not. The nonwords were based on real words, with one vowel changed. In the experimental stimuli, the vowel change involved a Catalan-specific contrast that previous research had shown to be difficult for Spanish natives to perceive. In the control stimuli, the vowel switch involved contrasts common to Spanish and Catalan. The results indicated that the groups of bilinguals did not differ in their behavioral and event-related brain potential measurements for the control stimuli; both groups made very few errors and showed a larger N400 component for control nonwords than for control words. However, significant differences were observed for the experimental stimuli across groups: Specifically, Spanish-dominant bilinguals showed great difficulty in rejecting experimental nonwords. Indeed, these participants not only showed very high error rates for these stimuli, but also did not show an error-related negativity effect in their erroneous nonword decisions. However, both groups of bilinguals showed a larger correct-related negativity when making correct decisions about the experimental nonwords. The results suggest that although some aspects of a second language system may show a remarkable lack of plasticity (like the acquisition of some foreign contrasts), first-language representations seem to be more dynamic in their capacity of adapting and incorporating new information.
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Secondary eyewall formation in WRF simulations of Hurricanes Rita and Katrina (2005)
NASA Astrophysics Data System (ADS)
Abarca, Sergio F.; Corbosiero, Kristen L.
2011-04-01
An analysis is presented of two high-resolution hurricane simulations of Katrina and Rita (2005) that exhibited secondary eyewall formation (SEF). The results support the notion of vortex Rossby waves (VRWs) having an important role in SEF and suggest that VRW activity is a defining aspect of the moat. SEF occurs at a radius of ˜65 (80) km in Katrina (Rita), close to the hypothesized stagnation radius of VRWs. VRW activity appears to be the result of eye-eyewall mixing events, themselves a product of the release of barotropic instability. The convection in the radial region that becomes the moat is mainly in the form of VRWs propagating radially outward from the primary eyewall until the negative radial gradient of potential vorticity is no longer conducive for their propagation. These convectively coupled waves, originating and being expelled from the eyewall, are rotation dominated and have the coherency necessary to survive their passage through the strain-dominated region outside the eyewall.
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Ower, G D; Hunt, J; Sakaluk, S K
2017-02-01
Although the strength and form of sexual selection on song in male crickets have been studied extensively, few studies have examined selection on the morphological structures that underlie variation in males' song, particularly in wild populations. Geometric morphometric techniques were used to measure sexual selection on the shape, size and symmetry of both top and bottom tegmina in wild populations of sagebrush crickets, a species in which nuptial feeding by females imposes an unambiguous phenotypic marker on males. The size of the tegmina negatively covaried with song dominant frequency and positively covaried with song pulse duration. Sexual selection was more intense on the bottom tegmen, conceivably because it interacts more freely with the subtegminal airspace, which may play a role in song amplification. An expanded coastal/subcostal region was one of the phenotypes strongly favoured by disruptive selection on the bottom tegmen, an adaptation that may form a more effective seal with the thorax to prevent noise cancellation. Directional selection also favoured increased symmetry in tegminal shape. Assuming more symmetrical males are better able to buffer against developmental noise, the song produced by these males may make them more attractive to females. Despite the strong stabilizing selection documented previously on the dominant frequency of the song, stabilizing selection on the resonator that regulates dominant frequency was surprisingly absent. Nonetheless, wing morphology had an important influence on song structure and appears to be subject to significant linear and nonlinear sexual selection through female mate choice. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.
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Sandra, Dominiek
2010-01-01
Two experiments and two corpus studies focus on homophone dominance in the spelling of regularly inflected verb forms, the phenomenon that the higher-frequency homophone causes more intrusion errors on the lower-frequency one than vice versa. Experiment 1 was a speeded dictation task focusing on the Dutch imperative, a verb form whose formation rule is poorly known. A clear-cut effect of homophone dominance was found. This effect was equally strong when the target imperative was preceded by another imperative in the same sentence whose pronunciation reflected the spelling rule. Experiment 2 indicated that the effect of homophone dominance cannot be reduced to an effect of recency. Language users cannot discriminate a recently seen verb form when shown the two homophones. Instead, they choose the most frequent spelling pattern. In Corpus Study 1 a Google search on the world wide web revealed a sublexical effect of homophone dominance in the spelling errors on regular past tense forms. Corpus Study 2 demonstrated the validity of the search method. The sublexical effect of homophone dominance, involving units that cut across the stem-suffix boundary, lends itself naturally to a representational model of the connectionist or analogical processing tradition but is hard to reconcile with a rule-based account.
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McInerney, E M; Ince, B A; Shapiro, D J; Katzenellenbogen, B S
1996-12-01
We have characterized a human estrogen receptor (ER) mutant, V364E, which has a single amino acid substitution in its hormone-binding domain. This ER mutant is fully active or even superactive at saturating levels of estradiol (10(-8) M E2) yet has the capacity to act as a strong dominant negative inhibitor of the wild type ER. In transient transfection assays using ER-negative Chinese hamster ovary (CHO) cells and two different estrogen response element (ERE)-containing promoter reporter genes, V364E treated with 10(-8) M E2 exhibited approximately 250% and 100% of the activity of the wild type ER with these two promoter contexts, respectively. Despite the high activity of V364E when present alone in cells, coexpression of both V364E and wild type ER causes a significant decrease in overall ER-mediated transcriptional activity. On the TATA promoter, where V364E was more inhibitory, estrogen-stimulated activity was reduced by approximately 50% at a 1:1 ratio of mutant to wild type ER expression vector, and at a 10:1 ratio, 75% of ER activity was inhibited. V364E was expressed at lower levels than wild type ER and has a approximately 40-fold lower affinity for E2 compared with wild type ER. In promoter interference assays, V364E exhibited a strict dependence upon E2 for binding to an ERE. Surprisingly, even when V364E was unable to bind to ERE DNA (i.e. either at low E2 concentration or by mutation of its DNA-binding domain), this mutant retained full dominant negative activity. This highly active ER mutant is, thus, able to repress ER-mediated transcription when the mutant and wild type ER are present together in cells, even without DNA binding. Since competition for ERE binding and the formation of inactive heterodimers cannot fully account for the dominant negative activity of V364E, it is probable that altered interactions with proteins important in ER-mediated transcription play a key role in the repression of transcription by V364E. The properties and probable mechanism of action of V364E distinguish it from other previously described dominant negative inhibitors, in which competition for cis-acting DNA elements by transcriptionally inactive receptors played a large role in the resultant dominant negative phenotype.
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Lindow, Janet C; Dohrmann, Paul R; McHenry, Charles S
2015-07-03
Biophysical and structural studies have defined many of the interactions that occur between individual components or subassemblies of the bacterial replicase, DNA polymerase III holoenzyme (Pol III HE). Here, we extended our knowledge of residues and interactions that are important for the first step of the replicase reaction: the ATP-dependent formation of an initiation complex between the Pol III HE and primed DNA. We exploited a genetic selection using a dominant negative variant of the polymerase catalytic subunit that can effectively compete with wild-type Pol III α and form initiation complexes, but cannot elongate. Suppression of the dominant negative phenotype was achieved by secondary mutations that were ineffective in initiation complex formation. The corresponding proteins were purified and characterized. One class of mutant mapped to the PHP domain of Pol III α, ablating interaction with the ϵ proofreading subunit and distorting the polymerase active site in the adjacent polymerase domain. Another class of mutation, found near the C terminus, interfered with τ binding. A third class mapped within the known β-binding domain, decreasing interaction with the β2 processivity factor. Surprisingly, mutations within the β binding domain also ablated interaction with τ, suggesting a larger τ binding site than previously recognized. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Spin-phonon coupling and exchange interaction in Gd substituted YFe0.5Cr0.5O3
NASA Astrophysics Data System (ADS)
Singh, Karan; Sharma, Mohit K.; Mukherjee, K.
2018-02-01
We report the evolution of physical properties due to partial substitution of Gd on the Y site in a mixed metal oxide YFe0.5Cr0.5O3. This compound exhibits negative magnetization at low applied fields. Our investigations on Y1-xGdxFe0.5Cr0.5O3 (x = 0.0, 0.2, 0.4 and 0.6) compounds is carried out through magnetization and Raman spectroscopy studies. It is observed that even with 20% Gd substitution, the negative magnetization observed in YFe0.5Cr0.5O3 is suppressed. Due to magnetic rare earth ion Gd3+, additional exchange interaction of the form Gd-O-Fe/Cr dominates the magnetic interaction arising due to the transition metal ions. This results in positive magnetization in Gd-substituted compounds. Temperature dependent Raman spectroscopy along with magnetization studies revealed that the observed shifts of Raman mode is due to spin-phonon coupling. Hardening of Raman mode observed below 240 K in YFe0.5Cr0.5O3 weakens and softening of phonon modes was observed for Y0.4Gd0.6Fe0.5Cr0.5O3 compound. This implies that additional magnetic interactions due to Gd ions play a dominating role in dictating the behavior of the Gd-substituted compounds.
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Sharma, Geeta; Noohu, Majumi Mohamad
2014-09-01
Cryotherapy, in the form of ice massge is used to reduce inflammation after acute musculoskeletal injury or trauma. The potential negative effects of ice massage on proprioception are unknown, despite equivocal evidence supporting its effectiveness. The purpose of the study was to test the influence of cooling on weight discrimination ability and hence the performance in footballers. The study was of same subject experimental design (pretest-posttest design). Thirty male collegiate football players, whose mean age was 21.07 years, participated in the study. The participants were assessed for two functional performance tests, single leg hop test and crossed over hop test and weight discrimination ability before and after ice massage for 5 minutes on hamstrings muscle tendon. Pre cooling scores of Single Leg Hop Test of the dominant leg in the subjects was 166.65 (± 10.16) cm and post cooling scores of the dominant leg was 167.25 (± 11.77) cm. Pre cooling scores of Crossed Over Hop Test of the dominant leg in the subjects was 174.14 (± 8.60) cm and post cooling scores of the dominant leg was 174.45 (± 9.28) cm. Pre cooling scores of Weight Discrimination Differential Threshold of the dominant leg in the subjects was 1.625 ± 1.179 kg compared with post cooling scores of the dominant leg 1.85 (± 1.91) kg. Pre cooling scores of single leg hop and crossed over hop test of the dominant leg in the subjects compared with post cooling scores of the dominant leg showed no significant differences and it was also noted that the weight discrimination ability (weight discrimination differential threshold) didn't show any significant difference. All the values are reported as mean ± SD. This study provides additional evidence that proprioceptive acuity in the hamstring muscles (biceps femoris) remains largely unaffected after ice application to the hamstrings tendon (biceps femoris).
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Fernández, E N; Legarra, A; Martínez, R; Sánchez, J P; Baselga, M
2017-06-01
Inbreeding generates covariances between additive and dominance effects (breeding values and dominance deviations). In this work, we developed and applied models for estimation of dominance and additive genetic variances and their covariance, a model that we call "full dominance," from pedigree and phenotypic data. Estimates with this model such as presented here are very scarce both in livestock and in wild genetics. First, we estimated pedigree-based condensed probabilities of identity using recursion. Second, we developed an equivalent linear model in which variance components can be estimated using closed-form algorithms such as REML or Gibbs sampling and existing software. Third, we present a new method to refer the estimated variance components to meaningful parameters in a particular population, i.e., final partially inbred generations as opposed to outbred base populations. We applied these developments to three closed rabbit lines (A, V and H) selected for number of weaned at the Polytechnic University of Valencia. Pedigree and phenotypes are complete and span 43, 39 and 14 generations, respectively. Estimates of broad-sense heritability are 0.07, 0.07 and 0.05 at the base versus 0.07, 0.07 and 0.09 in the final generations. Narrow-sense heritability estimates are 0.06, 0.06 and 0.02 at the base versus 0.04, 0.04 and 0.01 at the final generations. There is also a reduction in the genotypic variance due to the negative additive-dominance correlation. Thus, the contribution of dominance variation is fairly large and increases with inbreeding and (over)compensates for the loss in additive variation. In addition, estimates of the additive-dominance correlation are -0.37, -0.31 and 0.00, in agreement with the few published estimates and theoretical considerations. © 2017 Blackwell Verlag GmbH.
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Synthesis of monopolar ultrasound pulses for therapy: the frequency-compounding transducer.
Lin, Kuang-Wei; Hall, Timothy L; McGough, Robert J; Xu, Zhen; Cain, Charles A
2014-07-01
In diagnostic ultrasound, broadband transducers capable of short acoustic pulse emission and reception can improve axial resolution and provide sufficient bandwidth for harmonic imaging and multi-frequency excitation techniques. In histotripsy, a cavitation-based ultrasound therapy, short acoustic pulses (<2 cycles) can produce precise tissue ablation wherein lesion formation only occurs when the applied peak negative pressure exceeds an intrinsic threshold of the medium. This paper investigates a frequency compounding technique to synthesize nearly monopolar (half-cycle) ultrasound pulses. More specifically, these pulses were generated using a custom transducer composed of 23 individual relatively-broadband piezoceramic elements with various resonant frequencies (0.5, 1, 1.5, 2, and 3 MHz). Each frequency component of the transducer was capable of generating 1.5-cycle pulses with only one high-amplitude negative half-cycle using a custom 23-channel high-voltage pulser. By varying time delays of individual frequency components to allow their principal peak negative peaks to arrive at the focus of the transducer constructively, destructive interference occurs elsewhere in time and space, resulting in a monopolar pulse approximation with a dominant negative phase (with measured peak negative pressure [P-]: peak positive pressure [P+] = 4.68: 1). By inverting the excitation pulses to individual elements, monopolar pulses with a dominant positive phase can also be generated (with measured P+: P- = 4.74: 1). Experiments in RBC phantoms indicated that monopolar pulses with a dominant negative phase were able to produce very precise histotripsy-type lesions using the intrinsic threshold mechanism. Monopolar pulses with a dominant negative phase can inhibit shock scattering during histotripsy, leading to more predictable lesion formation using the intrinsic threshold mechanism, while greatly reducing any constructive interference, and potential hot-spots elsewhere. Moreover, these monopolar pulses could have many potential benefits in ultrasound imaging, including axial resolution improvement, speckle reduction, and contrast enhancement in pulse inversion imaging.
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Bacterial Biofilms in Chronic Rhinosinusitis and Their Implications for Clinical Management.
Karunasagar, Abhilasha; Garag, Santosh S; Appannavar, Suma B; Kulkarni, Raghavendra D; Naik, Ashok S
2018-03-01
To study the microbiological profile in patients with chronic rhino-sinusitis. To correlate disease severity with the presence of biofilms and host risk factors. To assess outcome of Sinus Surgery 2 weeks post operatively in terms of presence of bacteria and their ability to form biofilm. Prospective study. 50 cases of chronic rhino-sinusitis requiring Functional Endoscopic Sinus Surgery admitted in SDM Hospital, Dharwad, Karnataka were studied using intra-operative mucosal samples for microbiological analysis. The organisms isolated were tested for biofilm forming ability using three in vitro tests. Severity of disease was assessed using SNOT 22 scoring system. Of 50 cases studied, 66% showed presence of chronic rhino-sinusitis with polyposis and had higher SNOT scores compared to those without polyps. Bacterial isolates were obtained from only 17 samples. Staphylococcus species was isolated from 16 samples and Klebsiella pneumoniae from one. 11 Staph spp. isolates showed biofilm forming ability in vitro. Postoperative events in 3 cases yielded biofilm-forming Staphylococcus. Staphylococcus was the most dominant organism isolated and 11 isolates were biofilm formers. Thus the detection of biofilm forming organisms can be considered as a negative prognostic indicator and should forewarn the surgeon about the risk of recurrence.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Liwei; Yang, Jin Kuk; Kabaleeswaran, Venkataraman
The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program. Mutations in Fas that disrupt the DISC cause autoimmune lymphoproliferative syndrome (ALPS). Here we show that the Fas-FADD death domain (DD) complex forms an asymmetric oligomeric structure composed of 5-7 Fas DD and 5 FADD DD, whose interfaces harbor ALPS-associated mutations. Structure-based mutations disrupt the Fas-FADD interaction in vitro and in living cells; the severity of a mutation correlates with the number of occurrences of a particular interaction in the structure. The highly oligomeric structure explains the requirementmore » for hexameric or membrane-bound FasL in Fas signaling. It also predicts strong dominant negative effects from Fas mutations, which are confirmed by signaling assays. The structure optimally positions the FADD death effector domain (DED) to interact with the caspase-8 DED for caspase recruitment and higher-order aggregation.« less
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Sinusoidal input describing function for hysteresis followed by elementary backlash
NASA Technical Reports Server (NTRS)
Ringland, R. F.
1976-01-01
The author proposes a new sinusoidal input describing function which accounts for the serial combination of hysteresis followed by elementary backlash in a single nonlinear element. The output of the hysteresis element drives the elementary backlash element. Various analytical forms of the describing function are given, depending on the a/A ratio, where a is the half width of the hysteresis band or backlash gap, and A is the amplitude of the assumed input sinusoid, and on the value of the parameter representing the fraction of a attributed to the backlash characteristic. The negative inverse describing function is plotted on a gain-phase plot, and it is seen that a relatively small amount of backlash leads to domination of the backlash character in the describing function. The extent of the region of the gain-phase plane covered by the describing function is such as to guarantee some form of limit cycle behavior in most closed-loop systems.
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The Relative Salience of Daily and Enduring Influences on Off-Job Reactions to Work Stress.
Calderwood, Charles; Ackerman, Phillip L
2016-12-01
Work stress is an important determinant of employee health and wellness. The occupational health community is recognizing that one contributor to these relationships may be the presence of negative off-job reactivity to work, which we argue involves continued thoughts directed towards work (cognitive reactivity), continued negative mood stemming from work (affective reactivity), and the alteration of post-work behaviours in response to work factors (behavioural reactivity). We explored the relative contributions of daily work stressors, affective traits, and subjective job stress perceptions to negative off-job reactivity. These relationships were evaluated in a study of hospital nurses (n = 75), who completed trait measures and then provided self-assessments of daily work stress and off-job reactions for four work days. The results of several multilevel analyses indicated that a main-effects model best described the data when predicting cognitive, affective, and behavioural reactivity from daily work stressors, affective traits, and subjective job stress perceptions. A series of multilevel dominance analyses revealed that subjective job stress perceptions dominated the prediction of behavioural reactivity, while trait negative affect dominated the prediction of affective reactivity. Theoretical implications and the relative salience of daily and enduring contributors to negative off-job reactivity are discussed. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
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Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome.
Franken, Romy; den Hartog, Alexander W; Radonic, Teodora; Micha, Dimitra; Maugeri, Alessandra; van Dijk, Fleur S; Meijers-Heijboer, Hanne E; Timmermans, Janneke; Scholte, Arthur J; van den Berg, Maarten P; Groenink, Maarten; Mulder, Barbara J M; Zwinderman, Aeilko H; de Waard, Vivian; Pals, Gerard
2015-04-01
It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome. However, treatment response is highly variable. This study investigates losartan effectiveness in genetically classified subgroups. In this predefined substudy of COMPARE, Marfan patients were randomized to daily receive losartan 100 mg or no losartan. Aortic root dimensions were measured by MRI at baseline and after 3 years. FBN1 mutations were classified based on fibrillin-1 protein effect into (1) haploinsufficiency, decreased amount of normal fibrillin-1, or (2) dominant negative, normal fibrillin-1 abundance with mutant fibrillin-1 incorporated in the matrix. A pathogenic FBN1 mutation was found in 117 patients, of whom 79 patients were positive for a dominant negative mutation (67.5%) and 38 for a mutation causing haploinsufficiency (32.5%). Baseline characteristics between treatment groups were similar. Overall, losartan significantly reduced aortic root dilatation rate (no losartan, 1.3±1.5 mm/3 years, n=59 versus losartan, 0.8±1.4 mm/3 years, n=58; P=0.009). However, losartan reduced only aortic root dilatation rate in haploinsufficient patients (no losartan, 1.8±1.5 mm/3 years, n=21 versus losartan 0.5±0.8 mm/3 years, n=17; P=0.001) and not in dominant negative patients (no losartan, 1.2±1.7 mm/3 years, n=38 versus losartan 0.8±1.3 mm/3 years, n=41; P=0.197). Marfan patients with haploinsufficient FBN1 mutations seem to be more responsive to losartan therapy for inhibition of aortic root dilatation rate compared with dominant negative patients. Additional treatment strategies are needed in Marfan patients with dominant negative FBN1 mutations. http://www.trialregister.nl/trialreg/index.asp; Unique Identifier: NTR1423. © 2015 American Heart Association, Inc.
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Stress axis regulation during social ascension in a group-living cichlid fish.
Culbert, Brett M; Gilmour, Kathleen M; Balshine, Sigal
2018-06-19
Animals living in groups often form social hierarchies, with characteristic behaviours and physiologies associated with rank. However, when social opportunities arise and a subordinate ascends into a dominant position, quick adjustments are necessary to secure this position. Such periods of social transition are typically associated with elevated glucocorticoid production, but the precise regulation of the stress axis during these occasions is not well understood. Using the group-living cichlid, Neolamprologus pulcher, the effects of social ascension on the stress axis were assessed. Ascenders rapidly filled experimentally created vacancies, adopting a dominant behavioural phenotype within 72 h-elevating aggression, activity, and workload, while receiving high rates of affiliative behaviours from their group members. Despite assuming behavioural dominance within their groups, ascenders displayed higher cortisol levels than dominants three days post-ascension. Additionally, compared to subordinates, ascenders had increased transcript abundance of steroidogenic acute regulatory protein (star) and cytochrome p450 side-chain cleavage enzyme (p450scc) in the head kidney, indicating activation of the stress axis. Cortisol levels were lowest in ascenders that displayed low rates of aggression, potentially reflecting the reestablishment of social stability in these groups. Increased transcript abundance of both glucocorticoid receptors (gr1 and gr2) in the brain's preoptic area (POA) of ascenders compared to dominants suggested an enhanced capacity for cortisol regulation via negative feedback. Our results reveal a regulatory cascade of behavioural and physiological interactions and highlight the importance of investigating the underlying mechanisms regulating the stress axis. Copyright © 2018. Published by Elsevier Inc.
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NASA Astrophysics Data System (ADS)
Husemann, B.; Davis, T. A.; Jahnke, K.; Dannerbauer, H.; Urrutia, T.; Hodge, J.
2017-09-01
We present single-dish 12CO(1-0) and 12CO(2-1) observations for 14 low-redshift quasi-stellar objects (QSOs). In combination with optical integral field spectroscopy, we study how the cold gas content relates to the star formation rate (SFR) and black hole accretion rate. 12CO(1-0) is detected in 8 of 14 targets and 12CO(2-1) is detected in 7 out of 11 cases. The majority of disc-dominated QSOs reveal gas fractions and depletion times matching normal star-forming systems. Two gas-rich major mergers show clear starburst signatures with higher than average gas fractions and shorter depletion times. Bulge-dominated QSO hosts are mainly undetected in 12CO(1-0), which corresponds, on average, to lower gas fractions than in disc-dominated counterparts. Their SFRs, however, imply shorter than average depletion times and higher star formation efficiencies. Negative QSO feedback through removal of cold gas seems to play a negligible role in our sample. We find a trend between black hole accretion rate and total molecular gas content for disc-dominated QSOs when combined with literature samples. We interpret this as an upper envelope for the nuclear activity and it is well represented by a scaling relation between the total and circumnuclear gas reservoir accessible for accretion. Bulge-dominated QSOs significantly differ from that scaling relation and appear uncorrelated with the total molecular gas content. This could be explained either by a more compact gas reservoir, blown out of the gas envelope through outflows, or a different interstellar medium phase composition.
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Cui, Liang-Wei; Sun, Qing-Lei; Li, Bao-Guo
2014-05-01
Different types of dominance hierarchies reflect different social relationships in primates. In this study, we clarified the hierarchy and social relationships in a one-male unit of captive Rhinopithecus bieti observed between August 1998 and March 1999. Mean frequency of agonistic behaviour among adult females was 0.13 interactions per hour. Adult females exhibited a linear hierarchy with a reversal of 10.9%, indicating an unstable relationship; therefore, R. bieti appears to be a relaxed/tolerant species. The lack of a relationship between the agonistic ratio of the adult male towards adult females and their ranks indicated that males did not show increased aggression towards low-ranking females. Differentiated female affiliative relationships were loosely formed in terms of the male, and to some extent influenced by female estrus, implying that relationships between the male and females is influenced by estrus and not rank alone. A positive correlation between the agonistic ratio of adult females and their ranks showed that the degree to which one female negatively impacted others decreased with reduction in rank. Similarly, a positive correlation between the agonistic ratio of females and differences in rank suggests that a female had fewer negative effects on closely ranked individuals than distantly ranked ones. These data indicate that rank may influence relationships between females. A steeper slope of regression between the agonistic ratio and inter-female rank differences indicated that the extent of the power difference in high-ranking females exerting negative effects on low-ranking ones was larger during the mating season than the birth season, suggesting that rank may influence the mating success of females.
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CUI, Liang-Wei; SUN, Qing-Lei; LI, Bao-Guo
2014-01-01
Different types of dominance hierarchies reflect different social relationships in primates. In this study, we clarified the hierarchy and social relationships in a one-male unit of captive Rhinopithecus bieti observed between August 1998 and March 1999. Mean frequency of agonistic behaviour among adult females was 0.13 interactions per hour. Adult females exhibited a linear hierarchy with a reversal of 10.9%, indicating an unstable relationship; therefore, R. bieti appears to be a relaxed/tolerant species. The lack of a relationship between the agonistic ratio of the adult male towards adult females and their ranks indicated that males did not show increased aggression towards low-ranking females. Differentiated female affiliative relationships were loosely formed in terms of the male, and to some extent influenced by female estrus, implying that relationships between the male and females is influenced by estrus and not rank alone. A positive correlation between the agonistic ratio of adult females and their ranks showed that the degree to which one female negatively impacted others decreased with reduction in rank. Similarly, a positive correlation between the agonistic ratio of females and differences in rank suggests that a female had fewer negative effects on closely ranked individuals than distantly ranked ones. These data indicate that rank may influence relationships between females. A steeper slope of regression between the agonistic ratio and inter-female rank differences indicated that the extent of the power difference in high-ranking females exerting negative effects on low-ranking ones was larger during the mating season than the birth season, suggesting that rank may influence the mating success of females. PMID:24866491
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Farías, María E; Rascovan, Nicolás; Toneatti, Diego M; Albarracín, Virginia H; Flores, María R; Poiré, Daniel G; Collavino, Mónica M; Aguilar, O Mario; Vazquez, Martin P; Polerecky, Lubos
2013-01-01
We describe stromatolites forming at an altitude of 3570 m at the shore of a volcanic lake Socompa, Argentinean Andes. The water at the site of stromatolites formation is alkaline, hypersaline, rich in inorganic nutrients, very rich in arsenic, and warm (20-24°C) due to a hydrothermal input. The stromatolites do not lithify, but form broad, rounded and low-domed bioherms dominated by diatom frustules and aragonite micro-crystals agglutinated by extracellular substances. In comparison to other modern stromatolites, they harbour an atypical microbial community characterized by highly abundant representatives of Deinococcus-Thermus, Rhodobacteraceae, Desulfobacterales and Spirochaetes. Additionally, a high proportion of the sequences that could not be classified at phylum level showed less than 80% identity to the best hit in the NCBI database, suggesting the presence of novel distant lineages. The primary production in the stromatolites is generally high and likely dominated by Microcoleus sp. Through negative phototaxis, the location of these cyanobacteria in the stromatolites is controlled by UV light, which greatly influences their photosynthetic activity. Diatoms, dominated by Amphora sp., are abundant in the anoxic, sulfidic and essentially dark parts of the stromatolites. Although their origin in the stromatolites is unclear, they are possibly an important source of anaerobically degraded organic matter that induces in situ aragonite precipitation. To the best of our knowledge, this is so far the highest altitude with documented actively forming stromatolites. Their generally rich, diverse and to a large extent novel microbial community likely harbours valuable genetic and proteomic reserves, and thus deserves active protection. Furthermore, since the stromatolites flourish in an environment characterized by a multitude of extremes, including high exposure to UV radiation, they can be an excellent model system for studying microbial adaptations under conditions that, at least in part, resemble those during the early phase of life evolution on Earth.
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Farías, María E.; Rascovan, Nicolás; Toneatti, Diego M.; Albarracín, Virginia H.; Flores, María R.; Poiré, Daniel G.; Collavino, Mónica M.; Aguilar, O. Mario; Vazquez, Martin P.; Polerecky, Lubos
2013-01-01
We describe stromatolites forming at an altitude of 3570 m at the shore of a volcanic lake Socompa, Argentinean Andes. The water at the site of stromatolites formation is alkaline, hypersaline, rich in inorganic nutrients, very rich in arsenic, and warm (20–24°C) due to a hydrothermal input. The stromatolites do not lithify, but form broad, rounded and low-domed bioherms dominated by diatom frustules and aragonite micro-crystals agglutinated by extracellular substances. In comparison to other modern stromatolites, they harbour an atypical microbial community characterized by highly abundant representatives of Deinococcus-Thermus, Rhodobacteraceae, Desulfobacterales and Spirochaetes. Additionally, a high proportion of the sequences that could not be classified at phylum level showed less than 80% identity to the best hit in the NCBI database, suggesting the presence of novel distant lineages. The primary production in the stromatolites is generally high and likely dominated by Microcoleus sp. Through negative phototaxis, the location of these cyanobacteria in the stromatolites is controlled by UV light, which greatly influences their photosynthetic activity. Diatoms, dominated by Amphora sp., are abundant in the anoxic, sulfidic and essentially dark parts of the stromatolites. Although their origin in the stromatolites is unclear, they are possibly an important source of anaerobically degraded organic matter that induces in situ aragonite precipitation. To the best of our knowledge, this is so far the highest altitude with documented actively forming stromatolites. Their generally rich, diverse and to a large extent novel microbial community likely harbours valuable genetic and proteomic reserves, and thus deserves active protection. Furthermore, since the stromatolites flourish in an environment characterized by a multitude of extremes, including high exposure to UV radiation, they can be an excellent model system for studying microbial adaptations under conditions that, at least in part, resemble those during the early phase of life evolution on Earth. PMID:23308236
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NASA Astrophysics Data System (ADS)
Abdelhady, Ahmed Awad
2016-03-01
The negative impacts of degradation in the coastal zone of the Red Sea are becoming well known in upper portions of the trophic web (e.g., humans and fish), but are less well known among the benthic primary consumers. In addition, the degree to which heavy metals are entering the trophic web can be better-quantified using macrobenthos. Two-gastropod genera encompassing Echinolittorina subnodosa and Planaxis sulcatus from three different localities on the Egyptian coast of the Red Sea were examined in order to deduce the impact of environmental deterioration on the morphology of shells. The examined sites include clean pristine, slightly polluted, and markedly polluted rocky shores. Phosphate/lead industry is the main source of pollution in this zone. Because landmarks on the rugose Echinolittorina are difficult to define and to ensure finer resolution of the analyses, a newly 'grid-based' landmarks was implemented. Both Canonical Variate Analysis (CVA) and Thin Plate Spline (TPS) were particularly capable to capture and terrace the minor morphological variations accurately. Two phenotypes portioned among the environmentally different populations were recognized and interpreted as ecotypes with many intermediate forms. The first ecotype has a higher spire and smaller aperture and dominating the pristine site North of Marsa Alam, whereas the second ecotype has a globular shell shape with big aperture and dominating the markedly polluted site. The intermediate forms dominating the slightly polluted site. The shape differences are interpreted as an adaptive differentiation to different metal concentrations. As the morphological variation between the two-ecotypes of both taxa is still minors, and both ecotypes occur together with many intermediate forms, the phenotypic divergence stage has not yet accomplished. The gradational shape change among the investigated populations was positively correlated with index of Pollution (IP). As the human activities were the main driver of the phenotypic changes, hence anthropogenic impact may shift the evolution and/or the extinction rates.
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Al Khatib, Shadi; Keles, Sevgi; Garcia-Lloret, Maria; Karakoc-Aydiner, Elif; Reisli, Ismail; Artac, Hasibe; Camcioglu, Yildiz; Cokugras, Haluk; Somer, Ayper; Kutukculer, Necil; Yilmaz, Mustafa; Ikinciogullari, Aydan; Yegin, Olcay; Yüksek, Mutlu; Genel, Ferah; Kucukosmanoglu, Ercan; Baki, Ali; Bahceciler, Nerin N; Rambhatla, Anupama; Nickerson, Derek W; McGhee, Sean; Barlan, Isil B; Chatila, Talal
2009-08-01
The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired T(H)17 differentiation. To elucidate mechanisms underlying different forms of HIES. A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, respectively. Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired T(H)17 responses, but whereas STAT3 mutations abrogated early steps in T(H)17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired T(H)17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome.
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Margot, Heike; Stephan, Roger; Tasara, Taurai
2016-09-06
Fresh sprouted seeds have been associated with a number of large outbreaks caused by Salmonella and Shiga toxin-producing E. coli. However, the high number of commensal bacteria found on sprouted seeds hampers the detection of these pathogens. Knowledge about the composition of the sprout microbiome is limited. In this study, the microbiome of mungo bean sprouts and the impact of buffered peptone water (BPW) and Enterobacteriaceae enrichment broth (EE-broth)-based enrichment protocols on this microbiome were investigated. Assessments based on aerobic mesophilic colony counts showed similar increases in mungo bean sprout background flora levels independent of the enrichment protocol used. 16S rRNA sequencing revealed a mungo bean sprout microbiome dominated by Proteobacteria and Bacteroidetes. EE-broth enrichment of such samples preserved and increased Proteobacteria dominance while reducing Bacteroidetes and Firmicutes relative abundances. BPW enrichment, however, increased Firmicutes relative abundance while decreasing Proteobacteria and Bacteroidetes levels. Both enrichments also lead to various genus level changes within the Protobacteria and Firmicutes phyla. New insights into the microbiome associated with mungo bean sprout and how it is influenced through BPW and EE-broth-based enrichment strategies used for detecting Gram-negative pathogens were generated. BPW enrichment leads to Firmicutes and Proteobacteria dominance, whereas EE-broth enrichment preserves Proteobacteria dominance in the mungo bean sprout samples. By increasing the relative abundance of Firmicutes, BPW also increases the abundance of Gram-positive organisms including some that might inhibit recovery of Gram-negative pathogens. The use of EE-broth, although preserving and increasing the dominance of Proteobacteria, can also hamper the detection of lowly abundant Gram-negative target pathogens due to outgrowth of such organisms by the highly abundant non-target Proteobacteria genera comprising the mungo bean sprout associated background flora.
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Rashid, Ban Mousa; Rashid, Nawshirwan Gafoor; Schulz, Ansgar; Lahr, Georgia; Nore, Beston Faiek
2013-01-09
Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton. The absence or malfunction of osteoclasts is found to be strongly associated with the disease evolution. Currently, four clinically distinct forms of the disease have been recognized: the infantile autosomal recessive osteopetrosis, the malignant and the intermediate forms, and autosomal dominant osteopetrosis, type I and type II forms. The autosomal recessive types are the most severe forms with symptoms in very early childhood, whereas the autosomal dominant classes exhibit a heterogeneous trait with milder symptoms, often at later childhood or adulthood. Case 1 is the 12-year-old daughter (index patient) of an Iraqi-Kurdish family who, at the age of eight years, was diagnosed clinically to have mild autosomal dominant osteopetrosis. Presently, at 12-years old, she has severe complications due to the disease progression. In addition, the same family previously experienced the death of a female child in her late childhood. The deceased child had been misdiagnosed, at that time, with thalassemia major. In this report, we extended our investigation to identify the type of the inheritance patterns of osteopetrosis using molecular techniques, because consanguineous marriages exist within the family history. We have detected one heterozygous mutation in exon 15 of the Chloride Channel 7 gene in the index patient (Case 1), whereas other mutations were not detected in the associated genes TCIRG1, OSTM1, RANK, and RANKL. The missense mutation (CGG>TGG) located in exon 15 (c.1225C>T) of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T).Case 2 is the 16-year-old son (brother of the index patient) of the same family who was diagnosed clinically with mild autosomal dominant osteopetrosis. We have identified the same heterozygous mutation in exon 15 of the Chloride channel 7 gene in this patient (Case 2). The missense mutation (CGG>TGG) located in exon 15 (c.1225C>T) of the Chloride channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T).In addition to the clinical diagnosis of both cases, the missense mutation we identified in one allele of the Chloride channel 7 gene could be linked to autosomal dominant osteopetrosis-II because the symptoms appear in late childhood or adolescence. In this family, the molecular diagnosis was confirmed after identification of the same mutation in the older son (sibling). Furthermore, we detected that the father and his brother (the uncle) are carriers of the same mutation, whereas the mother and her sister (the aunt) do not carry any mutation of the Chloride channel 7 gene. Thus, the disease penetrance is at least 60% in the family. The mother and father are cousins and a further consanguineous marriage between the aunt and the uncle is not recommended because the dominant allele of the Chloride channel 7 gene will be transferred to the progeny. However, a similar risk is also expected following a marriage between the uncle and an unrelated woman. The p.R409W mutation in the Chloride channel 7 gene has not yet been described in the literature and it possibly has a dominant-negative impact on the protein.
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Modeling of surface-dominated plasmas: from electric thruster to negative ion source.
Taccogna, F; Schneider, R; Longo, S; Capitelli, M
2008-02-01
This contribution shows two important applications of the particle-in-cell/monte Carlo technique on ion sources: modeling of the Hall thruster SPT-100 for space propulsion and of the rf negative ion source for ITER neutral beam injection. In the first case translational degrees of freedom are involved, while in the second case inner degrees of freedom (vibrational levels) are excited. Computational results show how in both cases, plasma-wall and gas-wall interactions play a dominant role. These are secondary electron emission from the lateral ceramic wall of SPT-100 and electron capture from caesiated surfaces by positive ions and atoms in the rf negative ion source.
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Rasul, Golam; Glover, Karl D; Krishnan, Padmanaban G; Wu, Jixiang; Berzonsky, William A; Ibrahim, Amir M H
2015-12-01
Elevated level of late maturity α-amylase activity (LMAA) can result in low falling number scores, reduced grain quality, and downgrade of wheat (Triticum aestivum L.) class. A mating population was developed by crossing parents with different levels of LMAA. The F2 and F3 hybrids and their parents were evaluated for LMAA, and data were analyzed using the R software package 'qgtools' integrated with an additive-dominance genetic model and a mixed linear model approach. Simulated results showed high testing powers for additive and additive × environment variances, and comparatively low powers for dominance and dominance × environment variances. All variance components and their proportions to the phenotypic variance for the parents and hybrids were significant except for the dominance × environment variance. The estimated narrow-sense heritability and broad-sense heritability for LMAA were 14 and 54%, respectively. High significant negative additive effects for parents suggest that spring wheat cultivars 'Lancer' and 'Chester' can serve as good general combiners, and that 'Kinsman' and 'Seri-82' had negative specific combining ability in some hybrids despite of their own significant positive additive effects, suggesting they can be used as parents to reduce LMAA levels. Seri-82 showed very good general combining ability effect when used as a male parent, indicating the importance of reciprocal effects. High significant negative dominance effects and high-parent heterosis for hybrids demonstrated that the specific hybrid combinations; Chester × Kinsman, 'Lerma52' × Lancer, Lerma52 × 'LoSprout' and 'Janz' × Seri-82 could be generated to produce cultivars with significantly reduced LMAA level.
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Arresting a Torsin ATPase Reshapes the Endoplasmic Reticulum*
Rose, April E.; Zhao, Chenguang; Turner, Elizabeth M.; Steyer, Anna M.; Schlieker, Christian
2014-01-01
Torsins are membrane-tethered AAA+ ATPases residing in the nuclear envelope (NE) and endoplasmic reticulum (ER). Here, we show that the induction of a conditional, dominant-negative TorsinB variant provokes a profound reorganization of the endomembrane system into foci containing double membrane structures that are derived from the ER. These double-membrane sinusoidal structures are formed by compressing the ER lumen to a constant width of 15 nm, and are highly enriched in the ATPase activator LULL1. Further, we define an important role for a highly conserved aromatic motif at the C terminus of Torsins. Mutations in this motif perturb LULL1 binding, reduce ATPase activity, and profoundly limit the induction of sinusoidal structures. PMID:24275647
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Role of medial prefrontal cortex Narp in the extinction of morphine conditioned place preference.
Blouin, Ashley M; Han, Sungho; Pearce, Anne M; Cheng, Kailun; Lee, Jongah J; Johnson, Alexander W; Wang, Chuansong; During, Matthew J; Holland, Peter C; Shaham, Yavin; Baraban, Jay M; Reti, Irving M
2013-01-15
Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus (AAV) expressing wild-type (WT) Narp into the mPFC of Narp KO mice rescued the extinction and the injection of AAV expressing a dominant negative form of Narp (NarpN) into the mPFC of WT mice impaired the extinction of morphine CPP. These findings suggest that Narp in the mPFC mediates the extinction of morphine CPP.
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Ki, Bo-Min; Kim, Yu Mi; Jeon, Jun Min; Ryu, Hee Wook; Cho, Kyung-Suk
2017-12-28
Soil burial is the most widely used disposal method for infected pig carcasses, but composting has gained attention as an alternative disposal method because pig carcasses can be decomposed rapidly and safely by composting. To understand the pig carcass decomposition process in soil burial and by composting, pilot-scale test systems that simulated soil burial and composting were designed and constructed in the field. The envelope material samples were collected using special sampling devices without disturbance, and bacterial community dynamics were analyzed by high-throughput pyrosequencing for 340 days. Based on the odor gas intensity profiles, it was estimated that the active and advanced decay stages were reached earlier by composting than by soil burial. The dominant bacterial communities in the soil were aerobic and/or facultatively anaerobic gram-negative bacteria such as Pseudomonas, Gelidibacter, Mucilaginibacter , and Brevundimonas . However, the dominant bacteria in the composting system were anaerobic, thermophilic, endospore-forming, and/or halophilic gram-positive bacteria such as Pelotomaculum, Lentibacillus, Clostridium , and Caldicoprobacter . Different dominant bacteria played important roles in the decomposition of pig carcasses in the soil and compost. This study provides useful comparative date for the degradation of pig carcasses in the soil burial and composting systems.
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Mitofusin gain and loss of function drive pathogenesis in Drosophila models of CMT2A neuropathy.
El Fissi, Najla; Rojo, Manuel; Aouane, Aїcha; Karatas, Esra; Poliacikova, Gabriela; David, Claudine; Royet, Julien; Rival, Thomas
2018-06-13
Charcot-Marie-Tooth disease type 2A (CMT2A) is caused by dominant alleles of the mitochondrial pro-fusion factor Mitofusin 2 (MFN2). To address the consequences of these mutations on mitofusin activity and neuronal function, we generate Drosophila models expressing in neurons the two most frequent substitutions (R94Q and R364W, the latter never studied before) and two others localizing to similar domains (T105M and L76P). All alleles trigger locomotor deficits associated with mitochondrial depletion at neuromuscular junctions, decreased oxidative metabolism and increased mtDNA mutations, but they differently alter mitochondrial morphology and organization. Substitutions near or within the GTPase domain (R94Q, T105M) result in loss of function and provoke aggregation of unfused mitochondria. In contrast, mutations within helix bundle 1 (R364W, L76P) enhance mitochondrial fusion, as demonstrated by the rescue of mitochondrial alterations and locomotor deficits by over-expression of the fission factor DRP1. In conclusion, we show that both dominant negative and dominant active forms of mitofusin can cause CMT2A-associated defects and propose for the first time that excessive mitochondrial fusion drives CMT2A pathogenesis in a large number of patients. © 2018 The Authors.
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Phadnis, Nitin; Fry, James D
2005-09-01
The dominance of deleterious mutations has important consequences for phenomena such as inbreeding depression, the evolution of diploidy, and levels of natural genetic variation. Kacser and Burns' metabolic theory provides a paradigmatic explanation for why most large-effect mutations are recessive. According to the metabolic theory, the recessivity of large-effect mutations is a consequence of a diminishing-returns relationship between flux through a metabolic pathway and enzymatic activity at any step in the pathway, which in turn is an inevitable consequence of long metabolic pathways. A major line of support for this theory was the demonstration of a negative correlation between homozygous effects and dominance of mutations in Drosophila, consistent with a central prediction of the metabolic theory. Using data on gene deletions in yeast, we show that a negative correlation between homozygous effects and dominance of mutations exists for all major categories of genes analyzed, not just those encoding enzymes. The relationship between dominance and homozygous effects is similar for duplicated and single-copy genes and for genes whose products are members of protein complexes and those that are not. A complete explanation of dominance therefore requires either a generalization of Kacser and Burns' theory to nonenzyme genes or a new theory.
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Li, Chih-Ying; Waid-Ebbs, Julia; Velozo, Craig A.; Heaton, Shelley C.
2016-01-01
Primary Objective Social problem solving deficits characterize individuals with traumatic brain injury (TBI). Poor social problem solving interferes with daily functioning and productive lifestyles. Therefore, it is of vital importance to use the appropriate instrument to identify deficits in social problem solving for individuals with TBI. This study investigates factor structure and item-level psychometrics of the Social Problem Solving Inventory-Revised Short Form (SPSI-R:S), for adults with moderate and severe TBI. Research Design Secondary analysis of 90 adults with moderate and severe TBI who completed the SPSI-R:S. Methods and Procedures An exploratory factor analysis (EFA), principal components analysis (PCA) and Rasch analysis examined the factor structure and item-level psychometrics of the SPSI-R:S. Main Outcomes and Results The EFA showed three dominant factors, with positively worded items represented as the most definite factor. The other two factors are negative problem solving orientation and skills; and negative problem solving emotion. Rasch analyses confirmed the three factors are each unidimensional constructs. Conclusions The total score interpretability of the SPSI-R:S may be challenging due to the multidimensional structure of the total measure. Instead, we propose using three separate SPSI-R:S subscores to measure social problem solving for the TBI population. PMID:26052731
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Surface charge effects in protein adsorption on nanodiamonds.
Aramesh, M; Shimoni, O; Ostrikov, K; Prawer, S; Cervenka, J
2015-03-19
Understanding the interaction of proteins with charged diamond nanoparticles is of fundamental importance for diverse biomedical applications. Here we present a thorough study of protein binding, adsorption kinetics and structure on strongly positively (hydrogen-terminated) and negatively (oxygen-terminated) charged nanodiamond particles using a quartz crystal microbalance by dissipation and infrared spectroscopy. By using two model proteins (bovine serum albumin and lysozyme) of different properties (charge, molecular weight and rigidity), the main driving mechanism responsible for the protein binding to the charged nanoparticles was identified. Electrostatic interactions were found to dominate the protein adsorption dynamics, attachment and conformation. We developed a simple electrostatic model that can qualitatively explain the observed adsorption behaviour based on charge-induced pH modifications near the charged nanoparticle surfaces. Under neutral conditions, the local pH around the positively and negatively charged nanodiamonds becomes very high (11-12) and low (1-3) respectively, which has a profound impact on the protein charge, hydration and affinity to the nanodiamonds. Small proteins (lysozyme) were found to form multilayers with significant conformational changes to screen the surface charge, while larger proteins (albumin) formed monolayers with minor conformational changes. The findings of this study provide a step forward toward understanding and eventually predicting nanoparticle interactions with biofluids.
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Li, Chih-Ying; Waid-Ebbs, Julia; Velozo, Craig A; Heaton, Shelley C
2016-01-01
Social problem-solving deficits characterise individuals with traumatic brain injury (TBI), and poor social problem solving interferes with daily functioning and productive lifestyles. Therefore, it is of vital importance to use the appropriate instrument to identify deficits in social problem solving for individuals with TBI. This study investigates factor structure and item-level psychometrics of the Social Problem Solving Inventory-Revised: Short Form (SPSI-R:S), for adults with moderate and severe TBI. Secondary analysis of 90 adults with moderate and severe TBI who completed the SPSI-R:S was performed. An exploratory factor analysis (EFA), principal components analysis (PCA) and Rasch analysis examined the factor structure and item-level psychometrics of the SPSI-R:S. The EFA showed three dominant factors, with positively worded items represented as the most definite factor. The other two factors are negative problem-solving orientation and skills; and negative problem-solving emotion. Rasch analyses confirmed the three factors are each unidimensional constructs. It was concluded that the total score interpretability of the SPSI-R:S may be challenging due to the multidimensional structure of the total measure. Instead, we propose using three separate SPSI-R:S subscores to measure social problem solving for the TBI population.
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Leicht-Young, Stacey A.; Pavlovic, Noel B.; Adams, Jean V.
2012-01-01
Competitive interactions between native plants and nonnative, invasive plant species have been extensively studied; however, within degraded landscapes, the effect of interspecific interactions among invasive plants is less explored. We investigated a competitive interaction between two sympatric, invasive mustard species that have similar life history strategies and growth forms: garlic mustard and damesrocket. Greenhouse experiments using a full range of reciprocal density ratios were conducted to investigate interspecific competition. Garlic mustard had a negative effect on the final biomass, number of leaves, and relative growth rate in height of damesrocket. Survival of damesrocket was not negatively affected by interspecific competition with garlic mustard; however, garlic mustard showed higher mortality because of intraspecific competition. These results indicated that although garlic mustard has been observed to be the dominant species in this landscape, it may not completely outcompete damesrocket in all situations. Studies of invasive species in competition are important in degraded landscapes because this is the common situation in many natural areas.
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New sophistry: self-deception in the nursing academy.
Garrett, Bernard M
2016-07-01
In this essay, I advance an argument against the expansion and acceptance of postmodern metaphysical antirealist ideologies in the development of nursing theory in North America. I suggest mystical theoretical explanations of care, the rejection of empirical epistemology, and a return to divinity in nursing represent an intellectual dead end, as these ideas do little to help resolve real-world health issues and also negate the need for the academic discrimination of bad ideas. I examine some of the philosophical foundations of nursing theory and deconstruct some of the more preternatural theories that have become established as the dominant conventional wisdom in the academy. It is argued that this can be characterized as a form of self-deception, and overall has had a negative impact on advancement of the nursing profession and public health care. Reasons behind the widespread acceptance of these irrational theoretical stances in nursing and the ongoing support for mystical therapeutic interventions are explored. © 2016 John Wiley & Sons Ltd.
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Okita, P.M.; Shanks, Wayne C.
1992-01-01
Carbonate and sulfide minerals from the Molango, Mexico, and TaoJiang, China, Mn deposits display similar and distinctive ??34S and ??13C patterns in intervals of manganese carbonate mineralization. ??13C-values for Mn-bearing carbonate range from -17.8 to +0.5??? (PDB), with the most negative values occurring in high-grade ore zones that are composed predominantly of rhodochrosite. In contrast, calcite from below, within and above Mn-carbonate zones at Molango has ??13C???0??? (PDB). Markedly negative ??13C data indicate that a large proportion of the carbon in Mn-carbonates was derived from organic matter oxidation. Diagenetic reactions using MnO2 and SO2-4 to oxidize sedimentary organic matter were the principle causes of such 12C enrichment. Pyrite content and sulfide ?? 34S-values also show distinctive variations. In unmineralized rocks, very negative ??34S-values (avg. < -21??? CDT) and abundant pyrite content suggest that pyrite formed from diagenetic, bacteriogenic sulfate reduction. In contrast, Mn-bearing horizons typically contain only trace amounts of pyrite (e.g., <0.5 wt% S with ??34S-values 34S-enriched, in some cases to nearly the value for contemporaneous seawater. 34S-enriched pyrite from the Mn-carbonate intervals indicates sulfide precipitation in an environment that underwent extensive SO2-4 reduction, and was largely a closed system with regard to exchange of sulfate and dissolved sulfide with normal seawater. The occasional occurrence of 34S-depleted pyrite within Mn-carbonate zones dominated by 34S-enriched pyrite is evidence that closed-system conditions were intermittent and limited to local pore waters and did not involve entire sedimentary basins. Mn-carbonate precipitation may have occluded porosity in the surficial sediments, thus establishing an effective barrier to SO2-4 exchange with overlying seawater. Similar isotopic and mineralogic characteristics from both the Molango and TaoJiang deposits, widely separated in geologic time and space, suggest they were formed similarly by MnO2 precipitation at the margins of dysaerobic to anoxic marine basins. Mn-carbonate formed predominantly by early-diagenetic reduction of Mn-oxides via oxidation of organic matter in near-surface sediments. In addition to MnCO3 precipitation, organic matter oxidation reactions resulted in oxidation of FeS to Fe-oxides such as magnetite, maghemite and hematite. The latter process explains anomalously low pyrite content and abundant Fe-oxide minerals in ore zones dominated by rhodochrosite. ?? 1992.
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Novel autosomal dominant TNNT1 mutation causing nemaline myopathy.
Konersman, Chamindra G; Freyermuth, Fernande; Winder, Thomas L; Lawlor, Michael W; Lagier-Tourenne, Clotilde; Patel, Shailendra B
2017-11-01
Nemaline myopathy (NEM) is one of the three major forms of congenital myopathy and is characterized by diffuse muscle weakness, hypotonia, respiratory insufficiency, and the presence of nemaline rod structures on muscle biopsy. Mutations in troponin T1 (TNNT1) is 1 of 10 genes known to cause NEM. To date, only homozygous nonsense mutations or compound heterozygous truncating or internal deletion mutations in TNNT1 gene have been identified in NEM. This extended family is of historical importance as some members were reported in the 1960s as initial evidence that NEM is a hereditary disorder. Proband and extended family underwent Sanger sequencing for TNNT1. We performed RT-PCR and immunoblot on muscle to assess TNNT1 RNA expression and protein levels in proband and father. We report a novel heterozygous missense mutation of TNNT1 c.311A>T (p.E104V) that segregated in an autosomal dominant fashion in a large family residing in the United States. Extensive sequencing of the other known genes for NEM failed to identify any other mutant alleles. Muscle biopsies revealed a characteristic pattern of nemaline rods and severe myofiber hypotrophy that was almost entirely restricted to the type 1 fiber population. This novel mutation alters a residue that is highly conserved among vertebrates. This report highlights not only a family with autosomal dominant inheritance of NEM, but that this novel mutation likely acts via a dominant negative mechanism. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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Truncating SLC5A7 mutations underlie a spectrum of dominant hereditary motor neuropathies.
Salter, Claire G; Beijer, Danique; Hardy, Holly; Barwick, Katy E S; Bower, Matthew; Mademan, Ines; De Jonghe, Peter; Deconinck, Tine; Russell, Mark A; McEntagart, Meriel M; Chioza, Barry A; Blakely, Randy D; Chilton, John K; De Bleecker, Jan; Baets, Jonathan; Baple, Emma L; Walk, David; Crosby, Andrew H
2018-04-01
To identify the genetic cause of disease in 2 previously unreported families with forms of distal hereditary motor neuropathies (dHMNs). The first family comprises individuals affected by dHMN type V, which lacks the cardinal clinical feature of vocal cord paralysis characteristic of dHMN-VII observed in the second family. Next-generation sequencing was performed on the proband of each family. Variants were annotated and filtered, initially focusing on genes associated with neuropathy. Candidate variants were further investigated and confirmed by dideoxy sequence analysis and cosegregation studies. Thorough patient phenotyping was completed, comprising clinical history, examination, and neurologic investigation. dHMNs are a heterogeneous group of peripheral motor neuron disorders characterized by length-dependent neuropathy and progressive distal limb muscle weakness and wasting. We previously reported a dominant-negative frameshift mutation located in the concluding exon of the SLC5A7 gene encoding the choline transporter (CHT), leading to protein truncation, as the likely cause of dominantly-inherited dHMN-VII in an extended UK family. In this study, our genetic studies identified distinct heterozygous frameshift mutations located in the last coding exon of SLC5A7 , predicted to result in the truncation of the CHT C-terminus, as the likely cause of the condition in each family. This study corroborates C-terminal CHT truncation as a cause of autosomal dominant dHMN, confirming upper limb predominating over lower limb involvement, and broadening the clinical spectrum arising from CHT malfunction.
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Ito, Takuto; Kawazu, Hidetaka; Murata, Takayuki; Iwata, Seiko; Arakawa, Saki; Sato, Yoshitaka; Kuzushima, Kiyotaka; Goshima, Fumi; Kimura, Hiroshi
2014-01-01
Epstein–Barr virus (EBV) predominantly infects B cells and causes B-cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK-cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV-positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV-encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV-negative cells using the cells conditionally expressing LMP1, and on CAEBV-derived EBV-positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV-negative cell line. PMID:24799376
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Net Ecosystem Production and Actionable Negative Emissions Strategies
NASA Astrophysics Data System (ADS)
DeCicco, J. M.; Heo, J.
2016-12-01
Negative emissions strategies, designed to increase the rate at which carbon dioxide (CO2) and other greenhouse gases are removed from the atmosphere, are an important aspect of broader strategies for mitigating climate change. Not only is CO2 the dominant greenhouse gas and the one most intimately tied to existing commercial energy use, but it is also part of the global carbon cycle. On the order of 200 PgC•yr-1 circulates between the atmosphere and the major carbon stocks of the terrestrial biosphere, oceans and geosphere. Anthropogenic flows of roughly 10 PgC•yr-1 from fossil fuel use and 1 PgC•yr-1 from land-use change significantly exceed the Earth's natural carbon sink, and this imbalance causes the buildup of carbon in the atmosphere. In addition to strategies for reducing CO2 emissions, increasing negative emissions through carbon dioxide removal (CDR) is crucial for reducing carbon cycle imbalance in the near term as well as meeting long-term goals such as a 2°C limit. Terrestrial carbon management is important for both reducing emissions and enhancing sinks. Photosynthesis in terrestrial ecosystems is the form of CDR that is now most actionable, referring to mechanisms that can be economically implemented at meaningful scales without technology breakthroughs. Net ecosystem production (NEP) is a crucial metric for guiding CDR involving the terrestrial biosphere, including options such as bioenergy with carbon capture and storage (BECCS) and other forms of bio-based mitigation. We derive the necessary conditions for effective implementation of this category of negative emissions measures, emphasizing the importance of NEP measurement, baselines and appropriate methods of carbon accounting. We present a method for quantitative spatio-temporal analysis of land-use and land-cover changes for estimating landscape-scale NEP; provide a preliminary baseline NEP estimate for the continental United States; apply the method to reveal a cautionary tale regarding NEP and biofuel production; and discuss the implications for negative emissions research and public policy going forward.
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Spectral Evidence for Ionization in Air-Filled Glow Discharge Tubes: Application to Sprites
NASA Astrophysics Data System (ADS)
Armstrong, R. A.; Williams, E. R.; Golka, R. K.; Williams, D. R.
2001-12-01
The question of ionization in sprites and the evidence for VLF backscatter from sprites has motivated a quantitative spectral analysis of the various (classical) regions of the glow discharge tube under DC excitation and at air densities appropriate for sprites in the mesosphere. A PR-650 colorimeter (Photo Research, Inc.) has enabled calibrated irradiance measurements for localized zones along the axis of the discharge tube--in the dominantly blue negative glow, in the Faraday dark space and in the red/pink positive column. Consistent with historical nomenclature, nitrogen first and second positive emission is dominant in the positive column (associated with neutral N2), and nitrogen first negative emission, with a prominent peak at 4278 A, is dominant in the blue negative glow (associated with ionized N2+). Whereas nitrogen first and second positive emission are also detected in the negative glow, no spectral evidence for ionization (no 4279, no 3914, no Meinel) is found in the red/pink positive column. This negative result is attributed not to an absence of ionization in the positive column, but rather to a sparse population of N2+ relative to neutral nitrogen in this region, and to the prominent emission in the blue part of the spectrum due to nitrogen second positive. A similar interpretation may be appropriate for the time-integrated spectra from the red body of sprites, also lacking direct evidence for ionization.
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Identification and paleoclimatic significance of magnetite nanoparticles in soils
NASA Astrophysics Data System (ADS)
Ahmed, Imad A. M.; Maher, Barbara A.
2018-02-01
In the world-famous sediments of the Chinese Loess Plateau, fossil soils alternate with windblown dust layers to record monsoonal variations over the last ˜3 My. The less-weathered, weakly magnetic dust layers reflect drier, colder glaciations. The fossil soils (paleosols) contain variable concentrations of nanoscale, strongly magnetic iron oxides, formed in situ during the wetter, warmer interglaciations. Mineralogical identification of the magnetic soil oxides is essential for deciphering these key paleoclimatic records. Formation of magnetite, a mixed Fe2+/Fe3+ ferrimagnet, has been linked to soil redox oscillations, and thence to paleorainfall. An opposite hypothesis states that magnetite can only form if the soil is water saturated for significant periods in order for Fe3+ to be reduced to Fe2+, and suggests instead the temperature-dependent formation of maghemite, an Fe3+-oxide, much of which ages subsequently into hematite, typically aluminum substituted. This latter, oxidizing pathway would have been temperature, but not rainfall dependent. Here, through structural fingerprinting and scanning transmission electron microscopy and electron energy loss spectroscopy analysis, we prove that magnetite is the dominant soil-formed ferrite. Maghemite is present in lower concentrations, and shows no evidence of aluminum substitution, negating its proposed precursor role for the aluminum-substituted hematite prevalent in the paleosols. Magnetite dominance demonstrates that magnetite formation occurs in well-drained, generally oxidizing soils, and that soil wetting/drying oscillations drive the degree of soil magnetic enhancement. The magnetic variations of the Chinese Loess Plateau paleosols thus record changes in monsoonal rainfall, over timescales of millions of years.
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NASA Astrophysics Data System (ADS)
Rožman, Marko
2016-01-01
Glycosphingolipid fragmentation behavior was investigated by combining results from analysis of a series of negative ion tandem mass spectra and molecular modeling. Fragmentation patterns extracted from 75 tandem mass spectra of mainly acidic glycosphingolipid species (gangliosides) suggest prominent cleavage of the glycosidic bonds with retention of the glycosidic oxygen atom by the species formed from the reducing end (B and Y ion formation). Dominant product ions arise from dissociation of sialic acids glycosidic bonds whereas product ions resulting from cleavage of other glycosidic bonds are less abundant. Potential energy surfaces and unimolecular reaction rates of several low-energy fragmentation pathways leading to cleavage of glycosidic bonds were estimated in order to explain observed dissociation patterns. Glycosidic bond cleavage in both neutral (unsubstituted glycosyl group) and acidic glycosphingolipids was the outcome of the charge-directed intramolecular nucleophilic substitution (SN2) mechanism. According to the suggested mechanism, the nucleophile in a form of carboxylate or oxyanion attacks the carbon at position one of the sugar ring, simultaneously breaking the glycosidic bond and yielding an epoxide. For gangliosides, unimolecular reaction rates suggest that dominant product ions related to the cleavage of sialic acid glycosidic bonds are formed via direct dissociation channels. On the other hand, low abundant product ions related to the dissociation of other glycosidic bonds are more likely to be the result of sequential dissociation. Although results from this study mainly contribute to the understanding of glycosphingolipid fragmentation chemistry, some mechanistic findings regarding cleavage of the glycosidic bond may be applicable to other glycoconjugates.
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Forming Facial Expressions Influences Assessment of Others' Dominance but Not Trustworthiness.
Ueda, Yoshiyuki; Nagoya, Kie; Yoshikawa, Sakiko; Nomura, Michio
2017-01-01
Forming specific facial expressions influences emotions and perception. Bearing this in mind, studies should be reconsidered in which observers expressing neutral emotions inferred personal traits from the facial expressions of others. In the present study, participants were asked to make happy, neutral, and disgusted facial expressions: for "happy," they held a wooden chopstick in their molars to form a smile; for "neutral," they clasped the chopstick between their lips, making no expression; for "disgusted," they put the chopstick between their upper lip and nose and knit their brows in a scowl. However, they were not asked to intentionally change their emotional state. Observers judged happy expression images as more trustworthy, competent, warm, friendly, and distinctive than disgusted expression images, regardless of the observers' own facial expression. Observers judged disgusted expression images as more dominant than happy expression images. However, observers expressing disgust overestimated dominance in observed disgusted expression images and underestimated dominance in happy expression images. In contrast, observers with happy facial forms attenuated dominance for disgusted expression images. These results suggest that dominance inferred from facial expressions is unstable and influenced by not only the observed facial expression, but also the observers' own physiological states.
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NASA Astrophysics Data System (ADS)
Grodnitskaya, I. D.; Trusova, M. Yu.
2009-09-01
Two types of bogs were studied in Tomsk oblast—Maloe Zhukovskoe (an eutrophic peat low-moor bog) and Ozernoe (an oligotrophic peat high-moor bog). The gram-negative forms of Proteobacteria were found to be dominant and amounted to more than 40% of the total population of the microorganisms investigated. In the peat bogs, the population and diversity of the hydrolytic microbial complex, especially of the number of micromycetes, were lower than those in the mineral soils. The changes in the quantitative indices of the total microbiological activity of the bogs were established. The microbial biomass and the intensity of its respiration differed and were also related to the depth of the sampling. In the Zhukovskoe peat low-moor bog, the maximal biomass of heterotrophic microorganisms (154 μg of C/g of peat) was found in the aerobic zone at a depth of 0 to 10 cm. In the Ozernoe bog, the maximal biomass was determined in the zone of anaerobiosis at a depth of 300 cm (1947 μ g of C/g of peat). The molecular-genetic method was used for the determination of the spectrum of the methanogens. Seven unidentified dominant forms were revealed. The species diversity of the methanogens was higher in the oligotrophic high-moor bog than in the eutrophic low-moor bog.
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NASA Astrophysics Data System (ADS)
Molnár, Dániel Cs; Sargent, Mark T.; Delhaize, Jacinta; Delvecchio, Ivan; Smolčić, Vernesa; Novak, Mladen; Schinnerer, Eva; Zamorani, Giovanni; Bondi, Marco; Herrera-Ruiz, Noelia; Murphy, Eric J.; Vardoulaki, Eleni; Karim, Alexander; Leslie, Sarah; Magnelli, Benjamin; Carollo, C. Marcella; Middelberg, Enno
2018-03-01
Using infrared data from the Herschel Space Observatory and Karl G. Jansky Very Large Array 3 GHz observations in the COSMOS field, we investigate the redshift evolution of the infrared-radio correlation (IRRC) for star-forming galaxies (SFGs) we classify as either spheroid- or disc-dominated based on their morphology. The sample predominantly consists of disc galaxies with stellar mass ≳ 1010 M⊙, and residing on the star-forming main sequence (MS). After the removal of AGN using standard approaches, we observe a significant difference between the redshift evolution of the median IR/radio ratio \\overline{q}_{TIR} of (i) a sample of ellipticals, plus discs with a substantial bulge component (`spheroid-dominated' SFGs) and, (ii) virtually pure discs and irregular systems (`disc-dominated' SFGs). The spheroid-dominated population follows a declining \\overline{q}_{TIR} versus z trend similar to that measured in recent evolutionary studies of the IRRC. However, for disc-dominated galaxies, where radio and IR emission should be linked to star formation in the most straightforward way, we measure very little change in \\overline{q}_{TIR}. This suggests that low-redshift calibrations of radio emission as a star formation rate (SFR) tracer may remain valid out to at least z ≃ 1-1.5 for pure star-forming systems. We find that the different redshift evolution of qTIR for the spheroid- and disc-dominated sample is mainly due to an increasing radio excess for spheroid-dominated galaxies at z ≳ 0.8, hinting at some residual AGN activity in these systems. This finding demonstrates that in the absence of AGN, the IRRC is independent of redshift, and that radio observations can therefore be used to estimate SFRs at all redshifts for genuinely star-forming galaxies.
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Dominant-Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax
NASA Astrophysics Data System (ADS)
Sellman, Bret R.; Mourez, Michael; John Collier, R.
2001-04-01
The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.
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NASA Technical Reports Server (NTRS)
Margolis, Stephen B.; Sacksteder, Kurt (Technical Monitor)
2000-01-01
A pulsating form of hydrodynamic instability has recently been shown to arise during liquid-propellant deflagration in those parameter regimes where the pressure-dependent burning rate is characterized by a negative pressure sensitivity. This type of instability can coexist with the classical cellular, or Landau form of hydrodynamic instability, with the occurrence of either dependent on whether the pressure sensitivity is sufficiently large or small in magnitude. For the inviscid problem, it has been shown that, when the burning rate is realistically allowed to depend on temperature as well as pressure, sufficiently large values of the temperature sensitivity relative to the pressure sensitivity causes like pulsating form of hydrodynamic instability to become dominant. In that regime, steady, planar burning becomes intrinsically unstable to pulsating disturbances whose wave numbers are sufficiently small. This analysis is extended to the fully viscous case, where it is shown that although viscosity is stabilizing for intermediate and larger wave number perturbations, the intrinsic pulsating instability for small wave numbers remains. Under these conditions, liquid-propellant combustion is predicted to be characterized by large unsteady cells along the liquid/gas interface.
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A class of dynamin-like GTPases involved in the generation of the tubular ER network
Hu, Junjie; Shibata, Yoko; Zhu, Peng-Peng; Voss, Christiane; Rismanchi, Neggy; Prinz, William A.; Rapoport, Tom A.; Blackstone, Craig
2009-01-01
The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER shaping defects as a novel neuropathogenic mechanism. PMID:19665976
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The roles played by highly truncated splice variants of G protein-coupled receptors
2012-01-01
Alternative splicing of G protein-coupled receptor (GPCR) genes greatly increases the total number of receptor isoforms which may be expressed in a cell-dependent and time-dependent manner. This increased diversity of cell signaling options caused by the generation of splice variants is further enhanced by receptor dimerization. When alternative splicing generates highly truncated GPCRs with less than seven transmembrane (TM) domains, the predominant effect in vitro is that of a dominant-negative mutation associated with the retention of the wild-type receptor in the endoplasmic reticulum (ER). For constitutively active (agonist-independent) GPCRs, their attenuated expression on the cell surface, and consequent decreased basal activity due to the dominant-negative effect of truncated splice variants, has pathological consequences. Truncated splice variants may conversely offer protection from disease when expression of co-receptors for binding of infectious agents to cells is attenuated due to ER retention of the wild-type co-receptor. In this review, we will see that GPCRs retained in the ER can still be functionally active but also that highly truncated GPCRs may also be functionally active. Although rare, some truncated splice variants still bind ligand and activate cell signaling responses. More importantly, by forming heterodimers with full-length GPCRs, some truncated splice variants also provide opportunities to generate receptor complexes with unique pharmacological properties. So, instead of assuming that highly truncated GPCRs are associated with faulty transcription processes, it is time to reassess their potential benefit to the host organism. PMID:22938630
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Guedes Aguiar, Bruno; Padmanabhan, Prasad K; Dumas, Carole; Papadopoulou, Barbara
2018-06-12
Valosin-containing protein (VCP)/p97/Cdc48 is one of the best-characterised type II cytosolic AAA+ ATPases most known for their role in ubiquitin-dependent protein quality control. Here, we provide functional insights into the role of the Leishmania VCP/p97 homologue (LiVCP) in the parasite intracellular development. We demonstrate that although LiVCP is an essential gene, Leishmania infantum promastigotes can grow with less VCP. In contrast, growth of axenic and intracellular amastigotes is dramatically affected upon decreased LiVCP levels in heterozygous and temperature sensitive (ts) LiVCP mutants or the expression of dominant negative mutants known to specifically target the second conserved VCP ATPase domain, a major contributor of the VCP overall ATPase activity. Interestingly, these VCP mutants are also unable to survive heat stress, and a ts VCP mutant is defective in amastigote growth. Consistent with LiVCP's essential function in amastigotes, LiVCP messenger ribonucleic acid undergoes 3'Untranslated Region (UTR)-mediated developmental regulation, resulting in higher VCP expression in amastigotes. Furthermore, we show that parasite mutant lines expressing lower VCP levels or dominant negative VCP forms exhibit high accumulation of polyubiquitinated proteins and increased sensitivity to proteotoxic stress, supporting the ubiquitin-selective chaperone function of LiVCP. Together, these results emphasise the crucial role LiVCP plays under heat stress and during the parasite intracellular development. © 2018 John Wiley & Sons Ltd.
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Moreb, Eirik Adim; Hoover, Benjamin; Yaseen, Adam; Valyasevi, Nisakorn; Roecker, Zoe; Menacho-Melgar, Romel; Lynch, Michael D
2017-12-15
Phage-derived "recombineering" methods are utilized for bacterial genome editing. Recombineering results in a heterogeneous population of modified and unmodified chromosomes, and therefore selection methods, such as CRISPR-Cas9, are required to select for edited clones. Cells can evade CRISPR-Cas-induced cell death through recA-mediated induction of the SOS response. The SOS response increases RecA dependent repair as well as mutation rates through induction of the umuDC error prone polymerase. As a result, CRISPR-Cas selection is more efficient in recA mutants. We report an approach to inhibiting the SOS response and RecA activity through the expression of a mutant dominant negative form of RecA, which incorporates into wild type RecA filaments and inhibits activity. Using a plasmid-based system in which Cas9 and recA mutants are coexpressed, we can achieve increased efficiency and consistency of CRISPR-Cas9-mediated selection and recombineering in E. coli, while reducing the induction of the SOS response. To date, this approach has been shown to be independent of recA genotype and host strain lineage. Using this system, we demonstrate increased CRISPR-Cas selection efficacy with over 10 000 guides covering the E. coli chromosome. The use of dominant negative RecA or homologues may be of broad use in bacterial CRISPR-Cas-based genome editing where the SOS pathways are present.
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NASA Astrophysics Data System (ADS)
Kerrich, R.; Jia, Y.; Wyman, D.
2001-12-01
Mantle plume activity was more intense in the Archean and komatiite-basalt volcanic sequences are a major component of many Archean greenstone belts. Tholeiitic basalts compositionally resemble Phanerozoic and Recent ocean plateau basalts, such as those of Ontong Java and Iceland. However, komatiite-basalt sequences are tectonically imbricated with bimodal arc lavas and associated trench turbidites. Interfingering of komatiite flows with boninite series flows, and primitive to evolved arc basalts has recently been identified in the 2.7 Ga Abitibi greenstone belt, demonstrating spatially and temporally associated plume and arc magmatism. These observations are consistent with an intra-oceanic arc migrating and capturing an ocean plateau, where the plateau jams the arc and imbricated plateau-arc crust forms a greenstone belt orogen. Melting of shallowly subducted plateau basalt crust (high Ba, Th, LREE) accounts for the areally extensive and voluminous syntectonic tonalite batholiths. In contrast, the adakite-Mg-andesite-Niobium enriched basalt association found in Archean greenstone belts and Cenozoic arcs are melts of LREE depleted MORB slab. Buoyant residue from anomalously hot mantle plume melting at > 100km rises to couple with the composite plume-arc crust to form the distinctively thick and refractory Archean continental lithospheric mantle. New geochemical data for structurally hosted ultramafic units along the N. American Cordillera, from S. California to the Yukon, show that these are obducted slices of sub-arc lithospheric mantle. Negatively fractionated HREE with high Al2O3/TiO2 ratios signify prior melt extraction, and variably enriched Th and LREE with negative Nb anomalies a subduction component in a convergent margin. A secular decrease of mantle plume activity and temperature results in plume-arc dominated geodynamics in the Archean with shallow subduction and thick CLM, whereas Phanerozoic convergent margins are dominated by arc-continent, arc-terrane, and terrane-terrane collision with steep subduction resulting in narrow belts of granitoids and obduction of lithospheric mantle.
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Chiu, Yu-Hsin; Alvarez-Baron, Claudia; Kim, Eun Young
2010-01-01
Large-conductance Ca2+-activated K+ (BKCa) channels regulate the physiology of many cell types. A single vertebrate gene variously known as Slo1, KCa1.1, or KCNMA1 encodes the pore-forming subunits of BKCa channel but is expressed in a potentially very large number of alternative splice variants. Two splice variants of Slo1, Slo1VEDEC and Slo1QEERL, which differ at the extreme COOH terminus, show markedly different steady-state expression levels on the cell surface. Here we show that Slo1VEDEC and Slo1QEERL can reciprocally coimmunoprecipitate, indicating that they form heteromeric complexes. Moreover, coexpression of even small amounts of Slo1VEDEC markedly reduces surface expression of Slo1QEERL and total Slo1 as indicated by cell-surface biotinylation assays. The effects of Slo1VEDEC on steady-state surface expression can be attributed primarily to the last five residues of the protein based on surface expression of motif-swapped constructs of Slo1 in human embryonic kidney (HEK) 293T cells. In addition, the presence of the VEDEC motif at the COOH terminus of Slo1 channels is sufficient to confer a dominant-negative effect on cell surface expression of itself or other types of Slo1 subunits. Treating cells with short peptides containing the VEDEC motif increased surface expression of Slo1VEDEC channels transiently expressed in HEK293T cells and increased current through endogenous BKCa channels in mouse podocytes. Slo1VEDEC and Slo1QEERL channels are removed from the HEK293T cell surface with similar kinetics and to a similar extent, which suggests that the inhibitory effect of the VEDEC motif is exerted primarily on forward trafficking into the plasma membrane. PMID:20051533
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NF-κB Regulates Caspase-4 Expression and Sensitizes Neuroblastoma Cells to Fas-Induced Apoptosis
Yang, Hai-Jie; Wang, Mian; Wang, Lei; Cheng, Bin-Feng; Lin, Xiao-Yu; Feng, Zhi-Wei
2015-01-01
Found in neurons and neuroblastoma cells, Fas-induced apoptosis and accompanied activation of NF-κB signaling were thought to be associated with neurodegenerative diseases. However, the detailed functions of NF-κB activation in Fas killing and the effect of NF-κB activation on its downstream events remain unclear. Here, we demonstrated that agonistic Fas antibody induces cell death in a dose-dependent way and NF-κB signaling is activated as well, in neuroblastoma cells SH-EP1. Unexpectedly, NF-κB activation was shown to be pro-apoptotic, as suggested by the reduction of Fas-induced cell death with either a dominant negative form of IκBα (DN-IκBα) or an IκB kinase-specific inhibitor. To our interest, when analyzing downstream events of NF-κB signaling, we found that DN-IκBα only suppressed the expression of caspase-4, but not other caspases. Vice versa, enhancement of NF-κB activity by p65 (RelA) overexpression increased the expression of caspase-4 at both mRNA and protein levels. More directly, results from dual luciferase reporter assay demonstrated the regulation of caspase-4 promoter activity by NF-κB. When caspase-4 activity was blocked by its dominant negative (DN) form, Fas-induced cell death was substantially reduced. Consistently, the cleavage of PARP and caspase-3 induced by Fas was also reduced. In contrast, the cleavage of caspase-8 remained unaffected in caspase-4 DN cells, although caspase-8 inhibitor could rescue Fas-induced cell death. Collectively, these data suggest that caspase-4 activity is required for Fas-induced cell apoptosis and caspase-4 may act upstream of PARP and caspase-3 and downstream of caspase-8. Overall, we demonstrate that NF-κB can mediate Fas-induced apoptosis through caspase-4 protease, indicating that caspase-4 is a new mediator of NF-κB pro-apoptotic pathway in neuroblastoma cells. PMID:25695505
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Takeda, M; Saito, Y; Sekine, R; Onitsuka, I; Maeda, R; Maéno, M
2000-06-01
We demonstrated previously that Xmsx-1 is involved in mesoderm patterning along the dorso-ventral axis, under the regulation of BMP-4 signaling. When Xmsx-1 RNA was injected into the dorsal blastomeres, a mass of muscle tissue formed instead of notochord. This activity was similar to that of Xwnt-8 reported previously. In this study, we investigated whether the activity of Xmsx-1 is related to the ventralizing signal and myogenesis promoting factor, Xwnt-8. Whole-mount in situ hybridization showed that Xmsx-1, Xwnt-8, and XmyoD were expressed in overlapping areas, including the ventro-lateral marginal zone at mid-gastrula stage. The expression of XmyoD was induced by the ectopic expression of either Xmsx-1 or Xwnt-8 in dorsal blastomeres, and Xwnt-8 was induced by the ectopic expression of Xmsx-1. On the other hand, the expression of Xmsx-1 was not affected by the loading of pCSKA-Xwnt-8 or dominant-negative Xwnt-8 (DN-Xwnt-8) RNA. In addition, Xmsx-1 RNA did not abrogate the formation of notochord if coinjected with DN-Xwnt-8 RNA. These results suggest that Xmsx-1 functions upstream of the Xwnt-8 signal. Furthermore, the antagonistic function of Xmsx-1 to the expression of organizer genes, such as Xlim-1 and goosecoid, was shown by in situ hybridization analysis and luciferase reporter assay using the goosecoid promoter construct. Finally if Xmsx-1/VP-16 fusion RNA, which was expected to function as a dominant-negative Xmsx-1, was injected into ventral blastomeres, a partial secondary axis formed in a significant number of embryos. In such embryos, the activity of luciferase, under the control of goosecoid promoter sequence, was significantly elevated at gastrula stage. These results led us to conclude that Xmsx-1 plays a central role in establishing dorso-ventral axis in gastrulating embryo, by suppressing the expression of organizer genes.
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Sánchez-Valdepeñas, Carmen; Punzón, Carmen; San-Antonio, Belén; Martin, Angel G; Fresno, Manuel
2007-03-01
It has been shown that phosphorylation of p65/RelA and c-Rel plays a role in the regulation of transcriptional activity of NF-kappaB independent on IkappaB degradation. In this study, we show that anti CD3/CD28 activation induces the transactivation activity of both p65/RelA and c-Rel in T cells using Gal4 dependent assays. Moreover, protein kinase C (PKC)zeta, Cot kinase and NF-kappaB-inducing kinase (NIK) seem to be involved in those processes in a different manner. Thus, transfection of dominant negative forms of Cot and PKCzeta inhibits CD3/CD28 induction of Gal4-p65 transactivation, whereas the kinase inactive versions of the 3 kinases inhibit induction of Gal4-c-Rel. Cot induction of Gal4-c-Rel transactivating activity seems to be mediated sequentially through PKCzeta and NIK activation, since dominant negative form of NIK blocks Cot and PKCzeta induction, whereas kinase inactive PKCzeta only blocks Cot activity. In contrast, the contribution of NIK to the transactivation function of p65/RelA seems to be negligible and more importantly NIK-KD did not inhibit induction by Cot and PKCzeta. Besides, the enhancing effect of Cot on Gal4-p65 was not decreased in mouse embryo fibroblasts from NIK deficient aly/aly mice in contrast with a greatest reduction on Gal4-c-Rel. By using Ser to Ala mutants in p65 and c-Rel transactivation domains, PKCzeta and NIK activities seem to be dependent of a restricted set of Ser in both proteins. In contrast, the enhancing effect of Cot seems to be less dependent of a particular set of Ser residues being partially abrogated by mutation of several Ser residues.
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Khwaja, Fatima S; Quann, Emily J; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel
2008-11-01
The p75 neurotrophin receptor (p75(NTR)) functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75(NTR) expression in several prostate cancer cell lines leading to p75(NTR)-mediated decreased survival. Using the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico database of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75(NTR) levels and inhibition of cell survival. Prostate (PC-3 and DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75(NTR)-associated loss of survival than breast (MCF-7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant-negative form of p75(NTR) before carprofen treatment partially rescued cell survival, showing a cause-and-effect relationship between carprofen induction of p75(NTR) levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF-7 and 3T3 cells. Furthermore, small interfering RNA knockdown of the p38 mitogen-activated protein kinase (MAPK) protein prevented induction of p75(NTR) by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 min. Expression of a dominant-negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75(NTR) protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75(NTR)-dependent apoptosis via the p38 MAPK pathway in prostate cancer cells.
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NASA Astrophysics Data System (ADS)
Feigenbaum, Eyal; Hiszpanski, Anna M.
2017-07-01
A phase accumulation tracking (PAT) algorithm is proposed and demonstrated for the retrieval of the effective index of fishnet metamaterials (FMMs) in order to avoid the multi-branch uncertainty problem. This algorithm tracks the phase and amplitude of the dominant propagation mode across the FMM slab. The suggested PAT algorithm applies to resonant guided wave networks having only one mode that carries the light between the two slab ends, where the FMM is one example of this metamaterials sub-class. The effective index is a net effect of positive and negative accumulated phase in the alternating FMM metal and dielectric layers, with a negative effective index occurring when negative phase accumulation dominates.
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Yang, Xin; Ouyang, Hongsheng; Chen, Fuwang; Pang, Daxing; Dong, Meichen; Yang, Susu; Liu, Xiaoyun; Peng, Zhiyuan; Wang, Fei; Zhang, Xiao; Ren, Linzhu
2014-06-01
We examined the role of HMG-CoA reductase (HMGCR) during porcine circovirus 2 (PCV2) infection. The results demonstrated that levels of endogenous HMGCR were not significantly different in PCV2-infected cells and mock-infected cells. However, the level of phosphorylated HMGCR, an inactivated form of HMGCR, was increased in PCV2-infected cells. Furthermore, HMGCR was upregulated by overexpression, silenced by siRNA or inactivated using its dominant-negative form in PK-15 cells. The results showed that PCV2 infection was inhibited by HMGCR overexpression, whereas it was significantly increased in HMGCR-silenced cells and HMGCR inhibitor-treated cells. Moreover, there was a robust apoptotic response at 48 h post-infection (p.i.) in HMGCR-inactivated cells, and this response was significantly greater than that observed in PK-15 cells. A modest apoptotic response was also observed in HMGCR-silenced cells. Caspase-3 activity was also analysed in PCV2-infected cells at 48 h p.i. As expected, caspase-3 activity was significantly increased in HMGCR-inactivated and -silenced cells compared with PK-15 cells. PCV2 replication was dose-dependently increased in HMGCR-inactivated cells when treated with increasing amounts of caspase-3 inhibitor. Altogether, HMGCR was negatively associated with PCV2 infection and PCV2-induced apoptotic cell death. These data demonstrated that HMGCR can be used as a candidate target for PCV2 disease control and antivirus research. Furthermore, the cells generated in this study can be used to evaluate the potential effects of HMGCR on PCV2 replication. © 2014 The Authors.
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Chapman, Neil R; Webster, Gill A; Gillespie, Peter J; Wilson, Brian J; Crouch, Dorothy H; Perkins, Neil D
2002-01-01
Members of both Myc and nuclear factor kappaB (NF-kappaB) families of transcription factors are found overexpressed or inappropriately activated in many forms of human cancer. Furthermore, NF-kappaB can induce c-Myc gene expression, suggesting that the activities of these factors are functionally linked. We have discovered that both c-Myc and v-Myc can induce a previously undescribed, truncated form of the RelA(p65) NF-kappaB subunit, RelA(p37). RelA(p37) encodes the N-terminal DNA binding and dimerization domain of RelA(p65) and would be expected to function as a trans-dominant negative inhibitor of NF-kappaB. Surprisingly, we found that RelA(p37) no longer binds to kappaB elements. This result is explained, however, by the observation that RelA(p37), but not RelA(p65), forms a high-molecular-mass complex with c-Myc. These results demonstrate a previously unknown functional and physical interaction between RelA and c-Myc with many significant implications for our understanding of the role that both proteins play in the molecular events underlying tumourigenesis. PMID:12027803
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Filstrup, Christopher T; Hillebrand, Helmut; Heathcote, Adam J; Harpole, W Stanley; Downing, John A
2014-04-01
Freshwater biodiversity loss potentially disrupts ecosystem services related to water quality and may negatively impact ecosystem functioning and temporal community turnover. We analysed a data set containing phytoplankton and zooplankton community data from 131 lakes through 9 years in an agricultural region to test predictions that plankton communities with low biodiversity are less efficient in their use of limiting resources and display greater community turnover (measured as community dissimilarity). Phytoplankton resource use efficiency (RUE = biomass per unit resource) was negatively related to phytoplankton evenness (measured as Pielou's evenness), whereas zooplankton RUE was positively related to phytoplankton evenness. Phytoplankton and zooplankton RUE were high and low, respectively, when Cyanobacteria, especially Microcystis sp., dominated. Phytoplankton communities displayed slower community turnover rates when dominated by few genera. Our findings, which counter findings of many terrestrial studies, suggest that Cyanobacteria dominance may play important roles in ecosystem functioning and community turnover in nutrient-enriched lakes. © 2014 John Wiley & Sons Ltd/CNRS.
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Leaños-Miranda, Alfredo; Ulloa-Aguirre, Alfredo; Ji, Tae H; Janovick, Jo Ann; Conn, P Michael
2003-07-01
Loss of function by 11 of 13 naturally occurring mutations in the human GnRH receptor (hGnRHR) was thought to result from impaired ligand binding or effector coupling, but actually results from receptor misrouting. Homo- or heterodimerization of mutant receptors with wild-type (WT) receptors occurs for other G protein-coupled receptors and may result in dominant-negative or -positive effects on the WT receptor. We tested the hypothesis that WT hGnRHR function was affected by misfolded hGnRHR mutants. hGnRHR mutants were found to inhibit the function of WT GnRHR (measured by activation of effector and ligand binding). Inhibition varied depending on the particular hGnRHR mutant coexpressed and the ratio of hGnRHR mutant to WT hGnRHR cDNA cotransfected. The hGnRHR mutants did not interfere with the function of genetically modified hGnRHRs bearing either a deletion of primate-specific Lys(191) or the carboxyl-terminal tail of the catfish GnRHR; these show intrinsically enhanced expression. Moreover, a peptidomimetic antagonist of GnRH enhanced the expression of WT hGnRHR, but not of genetically modified hGnRHR species. The dominant-negative effect of the naturally occurring receptor mutants occurred only for the WT hGnRHR, which has intrinsic low maturation efficiency. The data suggest that this dominant negative effect accompanies the diminished plasma membrane expression as a recent evolutionary event.
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An African grassland responds similarly to long-term fertilization to the Park Grass experiment.
Ward, David; Kirkman, Kevin; Tsvuura, Zivanai
2017-01-01
We compared the results of a long-term (65 years) experiment in a South African grassland with the world's longest-running ecological experiment, the Park Grass study at Rothamsted, U.K. The climate is warm and humid in South Africa and cool and temperate in England. The African grassland has been fertilized with two forms of nitrogen applied at four levels, phosphorus and lime in a crossed design in 96 plots. In 1951, about 84% of plant cover consisted of Themeda triandra, Tristachya leucothrix and Setaria nigrirostris. Currently, the dominant species are Panicum maximum, Setaria sphacelata and Eragrostis curvula, making up 71% of total biomass. As in the Park Grass experiment, we found a significant (additive) interaction effect on ANPP of nitrogen and phosphorus, and a (marginally significant) negative correlation between ANPP and species richness. Unlike the Park Grass experiment, there was no correlation between ANPP and species richness when pH was included as a covariate. There was also a significant negative effect of nitrogen amount and nitrogen form and a positive effect of lime on species richness and species diversity. Soil pH had an important effect on species richness. Liming was insufficient to balance the negative effects on species richness of nitrogen fertilization. There was a significant effect of pH on biomass of three abundant species. There were also significant effects of light on the biomass of four species, with only Panicum maximum having a negative response to light. In all of the abundant species, adding total species richness and ANPP to the model increased the amount of variance explained. The biomass of Eragrostis curvula and P. maximum were negatively correlated with species richness while three other abundant species increased with species richness, suggesting that competition and facilitation were active. Consistent with the results from the Park Grass and other long-term fertilization experiments of grasslands, we found a positive effect of soil pH and a negative effect of nitrogen amount on species richness, a more acutely negative effect on species richness of acidic ammonium sulphate fertilizer than limestone ammonium nitrate, a negative relationship between species richness and biomass, and a positive effect on species richness of lime interacting with nitrogen.
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Checkley, Mary Ann; Luttge, Benjamin G; Soheilian, Ferri; Nagashima, Kunio; Freed, Eric O
2010-04-25
The human immunodeficiency virus type 1 (HIV-1) maturation inhibitor bevirimat disrupts virus replication by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) Gag processing intermediate to mature CA. The observation that bevirimat delays but does not completely block CA-SP1 processing suggests that the presence of uncleaved CA-SP1 may disrupt the maturation process in trans. In this study, we validate this hypothesis by using a genetic approach to demonstrate that a non-cleavable CA-SP1 mutant exerts a dominant-negative effect on maturation of wild-type HIV-1. In contrast, a mutant in which cleavage can occur internally within SP1 is significantly less potent as a dominant-negative inhibitor. We also show that bevirimat blocks processing at both the major CA-SP1 cleavage site and the internal site. These data underscore the importance of full CA-SP1 processing for HIV-1 maturation and highlight the therapeutic potential of inhibitors that target this Gag cleavage event. Published by Elsevier Inc.
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NASA Astrophysics Data System (ADS)
Wimmer, C.; Schiesko, L.; Fantz, U.
2016-02-01
BATMAN (Bavarian Test Machine for Negative ions) is a test facility equipped with a 1/8 scale H- source for the ITER heating neutral beam injection. Several diagnostics in the boundary layer close to the plasma grid (first grid of the accelerator system) followed the transition from volume to surface dominated H- production starting with a Cs-free, cleaned source and subsequent evaporation of caesium, while the source has been operated at ITER relevant pressure of 0.3 Pa: Langmuir probes are used to determine the plasma potential, optical emission spectroscopy is used to follow the caesiation process, and cavity ring-down spectroscopy allows for the measurement of the H- density. The influence on the plasma during the transition from an electron-ion plasma towards an ion-ion plasma, in which negative hydrogen ions become the dominant negatively charged particle species, is seen in a strong increase of the H- density combined with a reduction of the plasma potential. A clear correlation of the extracted current densities (jH-, je) exists with the Cs emission.
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Wimmer, C; Schiesko, L; Fantz, U
2016-02-01
BATMAN (Bavarian Test Machine for Negative ions) is a test facility equipped with a 18 scale H(-) source for the ITER heating neutral beam injection. Several diagnostics in the boundary layer close to the plasma grid (first grid of the accelerator system) followed the transition from volume to surface dominated H(-) production starting with a Cs-free, cleaned source and subsequent evaporation of caesium, while the source has been operated at ITER relevant pressure of 0.3 Pa: Langmuir probes are used to determine the plasma potential, optical emission spectroscopy is used to follow the caesiation process, and cavity ring-down spectroscopy allows for the measurement of the H(-) density. The influence on the plasma during the transition from an electron-ion plasma towards an ion-ion plasma, in which negative hydrogen ions become the dominant negatively charged particle species, is seen in a strong increase of the H(-) density combined with a reduction of the plasma potential. A clear correlation of the extracted current densities (j(H(-)), j(e)) exists with the Cs emission.
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The positive and negative framing of affirmative action: a group dominance perspective.
Haley, Hillary; Sidanius, Jim
2006-05-01
Using a sample of 328 White, Latino, and Black Los Angeles County adults, the authors examined the tendency to employ various affirmative action "frames" (e.g., affirmative action as a "tie-breaking" device or as a quota-based policy). All three groups agreed about which frames cast affirmative action in a positive light and which cast it in a negative light. Although minorities had a tendency to frame affirmative action in terms that most people find morally acceptable, Whites had a tendency to frame affirmative action in terms most people find unacceptable. In addition, compared to minorities, Whites were less supportive of affirmative action regardless of how it was framed. LISREL modeling also was employed to test two competing models regarding predictors of the tendency to use frames that one personally finds to be relatively negative versus positive. Consistent with the expectations of social dominance theory and a motivated cognition perspective, the authors found that social dominance orientation (SDO) had significant net direct and indirect effects on one's framing of affirmative action.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Min, Jungki; Perera, Lalith; Krahn, Juno M.
ABSTRACT Glucocorticoid receptor β (GRβ) is associated with glucocorticoid resistance via dominant negative regulation of GRα. To better understand how GRβ functions as a dominant negative inhibitor of GRα at a molecular level, we determined the crystal structure of the ligand binding domain of GRβ complexed with the antagonist RU-486. The structure reveals that GRβ binds RU-486 in the same ligand binding pocket as GRα, and the unique C-terminal amino acids of GRβ are mostly disordered. Binding energy analysis suggests that these C-terminal residues of GRβ do not contribute to RU-486 binding. Intriguingly, the GRβ/RU-486 complex binds corepressor peptide withmore » affinity similar to that of a GRα/RU-486 complex, despite the lack of helix 12. Our biophysical and biochemical analyses reveal that in the presence of RU-486, GRβ is found in a conformation that favors corepressor binding, potentially antagonizing GRα function. This study thus presents an unexpected molecular mechanism by which GRβ could repress transcription.« less
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Tonin, Katarina; Stražar, Klemen; Burger, Helena; Vidmar, Gaj
2013-09-01
The aim of our study was to evaluate adaptive changes in the dominant shoulders of female professional overhead athletes, their mutual association, and relation between adaptive changes and shoulder injury. Thirty-six female professional volleyball and handball players were divided into two groups: 14 athletes were included in the symptomatic group (positive shoulder injury history and specific shoulder tests) and 22 athletes were included in the asymptomatic group (negative shoulder injury history and specific shoulder tests). Clinical examinations with specific shoulder tests, evaluation of rotational mobility, and symptoms of malposition and dyskinesis of the dominant scapula (SICK scapula syndrome) were performed. Glenohumeral rotators were isokinetically tested at 60 and 150°/s, with evaluation of stability ratios and rotator fatigability. On average, the participants had decreased internal rotation (P<0.001) and increased external rotation (P<0.001), lower spiking (P<0.01 at 60 and 150°/s) and conventional ratios (P≤0.01 at 60 and 150°/s), lower eccentric external rotator peak torques (eER) (P≤0.05 at 60 and 150°/s), and marginally lower eccentric internal rotator peak torques at 60°/s (P=0.061) on the dominant side compared with the nondominant side. The symptomatic group showed decreased ER (P=0.021), higher deficit of dominant eER at 60°/s (P=0.049), and higher fatigability of internal (P=0.013) and external rotators (P=0.028). The athletes with increased ER had more scapular lateralization (ρ=0.340, P=0.042), higher spiking ratios at 60°/s (ρ=0.349, P=0.037) and 150°/s (ρ=0.330, P=0.049), and lower cocking ratios at 60°/s (ρ=-0.477, P=0.003). Decreased dominant ER, higher deficit of dominant eccentric ER peak torques, and higher dominant rotator fatigability correlate with previous shoulder pain/injury. Different adaptive changes (rotational mobility, SICK scapula signs, and glenohumeral muscular imbalance) are inter-related. As a form of both prevention and rehabilitation for the athletes at risk, we recommend individually adjusted shoulder training on the basis of clinical and isokinetic testing.
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Izawa, Ei-Ichi; Watanabe, Shigeru
2008-05-01
Jungle crows (Corvus macrorhynchos) flexibly change their social forms depending on their age, time of the day, and the season. In the daytime, paired adults behave territorially and unpaired subadults form small flocks of ten birds, whereas at night hundreds of birds roost together. In the breeding season, pairings remain in their nest all day. This fission-fusion raises questions about the underlying social structure and the cognitive capability of jungle crows. In this study, dyadic encounters were used to investigate dominance relationships (linear or non-linear) and the underlying mechanisms in captive jungle crows. Fourteen crows were tested in 455 encounters (i.e., 5 encounters per dyad), and a stable linear dominance relationship emerged. Sex and aggressiveness were determinants as individual characteristics for dominance formation. Males dominated females, and more aggressive individuals dominated less aggressive ones. Aggressive interactions in dyads occurred primarily during the first encounter and drastically declined during subsequent encounters without any signs of a confidence effect. These results suggest that, in captive jungle crow, a linear form of dominance is intrinsically determined by sex and aggressiveness and maintained extrinsically by memories of past outcomes associated with specific individuals, implying individual recognition.
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Authoritarianism, dominance and assertiveness.
Ray, J J
1981-08-01
It is shown that there are definitions of the three constructs of authoritarianism, dominance and assertiveness which read very similarly; so much so that no distinction is immediately evident. It is proposed that authoritarianism might be conceived as aggressive dominance and at least some types of assertiveness as nonaggressive dominance. A new scale of Dominance suitable for general population use was produced, and compared with the existing Ray (1976) behavior inventory of authoritarianism. Both scales showed highly significant correlations with peer rated dominance and submission (the latter being negative in sign) but only the authoritarianism scale showed significant correlations with rated aggressiveness and rigidity. It was concluded that the new definitions could be operationalized into valid scales.
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Right Hemispheric Dominance in Processing of Unconscious Negative Emotion
ERIC Educational Resources Information Center
Sato, Wataru; Aoki, Satoshi
2006-01-01
Right hemispheric dominance in unconscious emotional processing has been suggested, but remains controversial. This issue was investigated using the subliminal affective priming paradigm combined with unilateral visual presentation in 40 normal subjects. In either left or right visual fields, angry facial expressions, happy facial expressions, or…
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Turan, Başak; Selçuki, Cenk
2014-09-01
Amino acids are constituents of proteins and enzymes which take part almost in all metabolic reactions. Glutamic acid, with an ability to form a negatively charged side chain, plays a major role in intra and intermolecular interactions of proteins, peptides, and enzymes. An exhaustive conformational analysis has been performed for all eight possible forms at B3LYP/cc-pVTZ level. All possible neutral, zwitterionic, protonated, and deprotonated forms of glutamic acid structures have been investigated in solution by using polarizable continuum model mimicking water as the solvent. Nine families based on the dihedral angles have been classified for eight glutamic acid forms. The electrostatic effects included in the solvent model usually stabilize the charged forms more. However, the stability of the zwitterionic form has been underestimated due to the lack of hydrogen bonding between the solute and solvent; therefore, it is observed that compact neutral glutamic acid structures are more stable in solution than they are in vacuum. Our calculations have shown that among all eight possible forms, some are not stable in solution and are immediately converted to other more stable forms. Comparison of isoelectronic glutamic acid forms indicated that one of the structures among possible zwitterionic and anionic forms may dominate over the other possible forms. Additional investigations using explicit solvent models are necessary to determine the stability of charged forms of glutamic acid in solution as our results clearly indicate that hydrogen bonding and its type have a major role in the structure and energy of conformers.
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Cell cycle-regulated proteolysis of mitotic target proteins.
Bastians, H; Topper, L M; Gorbsky, G L; Ruderman, J V
1999-11-01
The ubiquitin-dependent proteolysis of mitotic cyclin B, which is catalyzed by the anaphase-promoting complex/cyclosome (APC/C) and ubiquitin-conjugating enzyme H10 (UbcH10), begins around the time of the metaphase-anaphase transition and continues through G1 phase of the next cell cycle. We have used cell-free systems from mammalian somatic cells collected at different cell cycle stages (G0, G1, S, G2, and M) to investigate the regulated degradation of four targets of the mitotic destruction machinery: cyclins A and B, geminin H (an inhibitor of S phase identified in Xenopus), and Cut2p (an inhibitor of anaphase onset identified in fission yeast). All four are degraded by G1 extracts but not by extracts of S phase cells. Maintenance of destruction during G1 requires the activity of a PP2A-like phosphatase. Destruction of each target is dependent on the presence of an N-terminal destruction box motif, is accelerated by additional wild-type UbcH10 and is blocked by dominant negative UbcH10. Destruction of each is terminated by a dominant activity that appears in nuclei near the start of S phase. Previous work indicates that the APC/C-dependent destruction of anaphase inhibitors is activated after chromosome alignment at the metaphase plate. In support of this, we show that addition of dominant negative UbcH10 to G1 extracts blocks destruction of the yeast anaphase inhibitor Cut2p in vitro, and injection of dominant negative UbcH10 blocks anaphase onset in vivo. Finally, we report that injection of dominant negative Ubc3/Cdc34, whose role in G1-S control is well established and has been implicated in kinetochore function during mitosis in yeast, dramatically interferes with congression of chromosomes to the metaphase plate. These results demonstrate that the regulated ubiquitination and destruction of critical mitotic proteins is highly conserved from yeast to humans.
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Preferential degradation of cognitive networks differentiates Alzheimer's disease from ageing.
Chhatwal, Jasmeer P; Schultz, Aaron P; Johnson, Keith A; Hedden, Trey; Jaimes, Sehily; Benzinger, Tammie L S; Jack, Clifford; Ances, Beau M; Ringman, John M; Marcus, Daniel S; Ghetti, Bernardino; Farlow, Martin R; Danek, Adrian; Levin, Johannes; Yakushev, Igor; Laske, Christoph; Koeppe, Robert A; Galasko, Douglas R; Xiong, Chengjie; Masters, Colin L; Schofield, Peter R; Kinnunen, Kirsi M; Salloway, Stephen; Martins, Ralph N; McDade, Eric; Cairns, Nigel J; Buckles, Virginia D; Morris, John C; Bateman, Randall; Sperling, Reisa A
2018-05-01
Converging evidence from structural, metabolic and functional connectivity MRI suggests that neurodegenerative diseases, such as Alzheimer's disease, target specific neural networks. However, age-related network changes commonly co-occur with neuropathological cascades, limiting efforts to disentangle disease-specific alterations in network function from those associated with normal ageing. Here we elucidate the differential effects of ageing and Alzheimer's disease pathology through simultaneous analyses of two functional connectivity MRI datasets: (i) young participants harbouring highly-penetrant mutations leading to autosomal-dominant Alzheimer's disease from the Dominantly Inherited Alzheimer's Network (DIAN), an Alzheimer's disease cohort in which age-related comorbidities are minimal and likelihood of progression along an Alzheimer's disease trajectory is extremely high; and (ii) young and elderly participants from the Harvard Aging Brain Study, a cohort in which imaging biomarkers of amyloid burden and neurodegeneration can be used to disambiguate ageing alone from preclinical Alzheimer's disease. Consonant with prior reports, we observed the preferential degradation of cognitive (especially the default and dorsal attention networks) over motor and sensory networks in early autosomal-dominant Alzheimer's disease, and found that this distinctive degradation pattern was magnified in more advanced stages of disease. Importantly, a nascent form of the pattern observed across the autosomal-dominant Alzheimer's disease spectrum was also detectable in clinically normal elderly with clear biomarker evidence of Alzheimer's disease pathology (preclinical Alzheimer's disease). At the more granular level of individual connections between node pairs, we observed that connections within cognitive networks were preferentially targeted in Alzheimer's disease (with between network connections relatively spared), and that connections between positively coupled nodes (correlations) were preferentially degraded as compared to connections between negatively coupled nodes (anti-correlations). In contrast, ageing in the absence of Alzheimer's disease biomarkers was characterized by a far less network-specific degradation across cognitive and sensory networks, of between- and within-network connections, and of connections between positively and negatively coupled nodes. We go on to demonstrate that formalizing the differential patterns of network degradation in ageing and Alzheimer's disease may have the practical benefit of yielding connectivity measurements that highlight early Alzheimer's disease-related connectivity changes over those due to age-related processes. Together, the contrasting patterns of connectivity in Alzheimer's disease and ageing add to prior work arguing against Alzheimer's disease as a form of accelerated ageing, and suggest multi-network composite functional connectivity MRI metrics may be useful in the detection of early Alzheimer's disease-specific alterations co-occurring with age-related connectivity changes. More broadly, our findings are consistent with a specific pattern of network degradation associated with the spreading of Alzheimer's disease pathology within targeted neural networks.
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Scale Dependence of Dark Energy Antigravity
NASA Astrophysics Data System (ADS)
Perivolaropoulos, L.
2002-09-01
We investigate the effects of negative pressure induced by dark energy (cosmological constant or quintessence) on the dynamics at various astrophysical scales. Negative pressure induces a repulsive term (antigravity) in Newton's law which dominates on large scales. Assuming a value of the cosmological constant consistent with the recent SnIa data we determine the critical scale $r_c$ beyond which antigravity dominates the dynamics ($r_c \\sim 1Mpc $) and discuss some of the dynamical effects implied. We show that dynamically induced mass estimates on the scale of the Local Group and beyond are significantly modified due to negative pressure. We also briefly discuss possible dynamical tests (eg effects on local Hubble flow) that can be applied on relatively small scales (a few $Mpc$) to determine the density and equation of state of dark energy.
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Huntsinger, Jeffrey R
2012-11-01
The current research challenges the common view that positive affect and negative affect generate a broadened or narrowed attentional focus, respectively. Contrary to this view, two studies found that the link between affect and attentional focus as measured by a traditional flanker task (Study 1) and a modified flanker task (Study 2) reflects whatever focus is momentarily dominant. Further, in these studies when neither focus was dominant, the link between affect and attentional focus vanished. These results demonstrate that, like reward, positive affect and negative affect are not dedicated to a particular broadened or narrowed attentional scope but rather provide embodied information about the value of currently accessible attentional orientations. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
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Gendered endings: narratives of male and female suicides in the South African Lowveld.
Niehaus, Isak
2012-06-01
Durkheim's classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu's concepts of 'symbolic violence' and 'masculine domination' provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu's concept of 'habitus', the narrators of suicide stories did reflect critically upon gender constructs.
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C/EBPβ LIP augments cell death by inducing osteoglycin.
Wassermann-Dozorets, Rina; Rubinstein, Menachem
2017-04-06
Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription factor C/EBPβ regulates the expression of Ogn. C/EBPβ is expressed as a full-length, active form (LAP) and as a truncated, dominant-negative form (LIP), and the LIP/LAP ratio is positively correlated with the extent of cell death under stress. For example, we reported that drug-resistant tumor cells lack LIP altogether, and its supplementation abolished their resistance to chemotherapy and to endoplasmic reticulum (ER) stress. Here we further show that elevated LIP/LAP ratio robustly increased Ogn expression and cell death under stress by modulating the mitogen-activated protein kinase/activator protein 1 pathway (MAPK/AP-1). Our findings suggest that LIP deficiency renders tumor cell resistant to ER stress by preventing the induction of Ogn.
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Truncating SLC5A7 mutations underlie a spectrum of dominant hereditary motor neuropathies
Salter, Claire G.; Beijer, Danique; Hardy, Holly; Barwick, Katy E.S.; Bower, Matthew; Mademan, Ines; De Jonghe, Peter; Deconinck, Tine; Russell, Mark A.; McEntagart, Meriel M.; Chioza, Barry A.; Blakely, Randy D.; Chilton, John K.; De Bleecker, Jan; Baets, Jonathan; Baple, Emma L.
2018-01-01
Objective To identify the genetic cause of disease in 2 previously unreported families with forms of distal hereditary motor neuropathies (dHMNs). Methods The first family comprises individuals affected by dHMN type V, which lacks the cardinal clinical feature of vocal cord paralysis characteristic of dHMN-VII observed in the second family. Next-generation sequencing was performed on the proband of each family. Variants were annotated and filtered, initially focusing on genes associated with neuropathy. Candidate variants were further investigated and confirmed by dideoxy sequence analysis and cosegregation studies. Thorough patient phenotyping was completed, comprising clinical history, examination, and neurologic investigation. Results dHMNs are a heterogeneous group of peripheral motor neuron disorders characterized by length-dependent neuropathy and progressive distal limb muscle weakness and wasting. We previously reported a dominant-negative frameshift mutation located in the concluding exon of the SLC5A7 gene encoding the choline transporter (CHT), leading to protein truncation, as the likely cause of dominantly-inherited dHMN-VII in an extended UK family. In this study, our genetic studies identified distinct heterozygous frameshift mutations located in the last coding exon of SLC5A7, predicted to result in the truncation of the CHT C-terminus, as the likely cause of the condition in each family. Conclusions This study corroborates C-terminal CHT truncation as a cause of autosomal dominant dHMN, confirming upper limb predominating over lower limb involvement, and broadening the clinical spectrum arising from CHT malfunction. PMID:29582019
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Challenging dominant norms of masculinity for HIV prevention.
MacPhail, Catherine
2003-01-01
Within South Africa there is a growing HIV epidemic, particularly among young heterosexual people. A recent report (NMF/HSRC, 2002) indicates that levels of HIV infection among young people aged 15-24 years are 9.3% although other studies in more specific locations have shown levels to be higher than this. One of the best means of developing successful and innovative HIV prevention programmes for young people is to enhance our understandings of youth sexuality and the manner in which dominant norms contribute to the spread of sexually transmitted diseases. Social norms of masculinity are particularly important in this regard, as the manner in which 'normal' men are defined such as through acquisition of multiple partners, power over women and negative attitudes towards condoms, are often in conflict with the true emotional vulnerabilities of young men. Given the strong influence of peer groups on young people and the belief that one of the solutions to behaviour change lies in peer renegotiation of dominant norms, there is the need to begin to investigate young men who challenge dominant norms of masculinity. It is in investigating their points of view that a platform for the deconstruction of stereotypical masculinities and the reconstruction of new norms can be formed. The paper begins to consider these counter normative ideas through highlighting the discussions of young South African men aged 13-25 years in focus groups and in-depth individual interviews conducted in Gauteng Province. It is apparent that among this group there are young men challenging normative views of masculinity in a manner that could be harnessed within HIV prevention initiatives.
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Critiquing Human Resource Development's Dominant Masculine Rationality and Evaluating Its Impact
ERIC Educational Resources Information Center
Bierema, Laura L.
2009-01-01
The purpose of this article is to critique human resource development's (HRD) dominant philosophy, practices, and research; illustrate how they negatively affect women HRD practitioners and recipients; and recommend alternative conceptualizations of the field. This article is grounded in a critical feminist theoretical framework, draws on critical…
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Khan, Waqas; Khan, Shujaul Mulk; Ahmad, Habib; Alqarawi, Abdulaziz A; Shah, Ghulam Mujtaba; Hussain, Manzoor; Abd Allah, E F
2018-01-01
The life form and leaf size spectra of plant species of the Thandiani forests, district Abbottabad, were studied during the summer of 2013. These forests host 252 plant species of 97 families. Biological spectra showed that Hemicryptophytes (80 spp., 31.74%) were dominant followed by Megaphanerophytes (51 spp., 20.24%), Therophytes (49 spp., 19.44%) and Nanophanerophytes (45 spp., 17.86). Hemicryptophytes are the indicators of cold temperate vegetation. At the lower elevations, Megaphanerophytes and Nanophanerophytes were dominant which confirm trees as dominant habit form due to high soil depth, moisture and temperature factors. Data on Leaf spectra in the area showed that Microphyllous (88 spp., 34.92%) species were dominant followed by Leptophyllous (74 spp., 29.36%) and Nanophyllous (60 spp., 23.80%). The Microphyllous plants again are the indicator of cold temperate zone as the area is situated at an elevation of 1191-2626 m. Similarly, Nanophylls were dominant at lower elevations. Data on family importance values and diversity among various communities were also recorded. Life form and Leaf spectra studies could be used to understand the micro climatic variation of the region.
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Li, Rui-ling; Zhang, Yong-chun; Liu, Zhuang; Zeng, Yuan; Li, Wei-xin; Zhang, Hong-ling
2010-05-01
To investigate the effect of rainfall on agricultural nonpoint source pollution, watershed scale experiments were conducted to study the characteristics of nutrients in surface runoff under different rainfall intensities from farmlands in gentle slope hilly areas around Taihu Lake. Rainfall intensity significantly affected N and P concentrations in runoff. Rainfall intensity was positively related to TP, PO4(3-) -P and NH4+ -N event mean concentrations(EMC). However, this study have found the EMC of TN and NO3- -N to be positively related to rainfall intensity under light rain and negatively related to rainfall intensity under heavy rain. TN and TP site mean amounts (SMA) in runoff were positively related to rainfall intensity and were 1.91, 311.83, 127.65, 731.69 g/hm2 and 0.04, 7.77, 2.99, 32.02 g/hm2 with rainfall applied under light rain, moderate rain, heavy rain and rainstorm respectively. N in runoff was mainly NO3- -N and NH4+ -N and was primarily in dissolved form from Meilin soils. Dissolved P (DP) was the dominant form of TP under light rain, but particulate P (PP) mass loss increased with the increase of rainfall intensity and to be the dominant form when the rainfall intensity reaches rainstorm. Single relationships were used to describe the dependence of TN and TP mass losses in runoff on rainfall, maximum rainfall intensity, average rainfall intensity and rainfall duration respectively. The results showed a significant positive correlation between TN mass loss and rainfall, maximum rainfall intensity respectively (p < 0.01) and also TP mass loss and rainfall, maximum rainfall intensity respectively (p < 0.01).
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Declines in predatory fish promote bloom-forming macroalgae.
Eriksson, Britas Klemens; Ljunggren, Lars; Sandström, Alfred; Johansson, Gustav; Mattila, Johanna; Rubach, Anja; Råberg, Sonja; Snickars, Martin
2009-12-01
In the Baltic Sea, increased dominance of ephemeral and bloom-forming algae is presently attributed to increased nutrient loads. Simultaneously, coastal predatory fish are in strong decline. Using field data from nine areas covering a 700-km coastline, we examined whether formation of macroalgal blooms could be linked to the composition of the fish community. We then tested whether predator or nutrient availability could explain the field patterns in two small-scale field experiments, by comparing joint effects on algal net production from nutrient enrichment with agricultural fertilizer and exclusion of larger predatory fish with cages. We also manipulated the presence of invertebrate grazers. The abundance of piscivorous fish had a strong negative correlation with the large-scale distribution of bloom-forming macroalgae. Areas with depleted top-predator communities displayed massive increases in their prey, small-bodied fish, and high covers of ephemeral algae. Combining the results from the two experiments showed that excluding larger piscivorous fish: (1) increased the abundance of small-bodied predatory fish; (2) changed the size distribution of the dominating grazers, decreasing the smaller gastropod scrapers; and (3) increased the net production of ephemeral macroalgae. Effects of removing top predators and nutrient enrichment were similar and additive, together increasing the abundance of ephemeral algae many times. Predator effects depended on invertebrate grazers; in the absence of invertebrates there were no significant effects of predator exclusion on algal production. Our results provide strong support for regional declines of larger predatory fish in the Baltic Sea promoting algal production by decreasing invertebrate grazer control. This highlights the importance of trophic interactions for ecosystem responses to eutrophication. The view emerges that to achieve management goals for water quality we need to consider the interplay between top-down and bottom-up processes in future ecosystem management of marine resources.
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A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.
Vissing, John; Barresi, Rita; Witting, Nanna; Van Ghelue, Marijke; Gammelgaard, Lise; Bindoff, Laurence A; Straub, Volker; Lochmüller, Hanns; Hudson, Judith; Wahl, Christoph M; Arnardottir, Snjolaug; Dahlbom, Kathe; Jonsrud, Christoffer; Duno, Morten
2016-08-01
Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings in 10 families, our study indicates that a dominantly inherited pattern of calpainopathy exists, and should be considered in the diagnostic work-up and genetic counselling of patients with calpainopathy and single-allele aberrations in CAPN3. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Wright, Aidan G C; Stepp, Stephanie D; Scott, Lori N; Hallquist, Michael N; Beeney, Joseph E; Lazarus, Sophie A; Pilkonis, Paul A
2017-10-01
Narcissism has significant interpersonal costs, yet little research has examined behavioral and affective patterns characteristic of narcissism in naturalistic settings. Here we studied the effect of narcissistic features on the dynamic processes of interpersonal behavior and affect in daily life. We used interpersonal theory to generate transactional models of social interaction (i.e., linkages among perceptions of others' behavior, affect, and one's own behavior) predicted to be characteristic of narcissism. Psychiatric outpatients (N = 102) completed clinical interviews and a 21-day ecological momentary assessment protocol using smartphones. After social interactions (N = 5,781), participants reported on perceptions of their interaction partner's behavior (scored along the dimensions of dominant-submissive and affiliative-quarrelsome), their own affect, and their own behavior. Multilevel structural equation modeling was used to examine dynamic links among behavior and affect across interactions, and the role of narcissism in moderating these links. Results showed that perceptions of others' dominance did not predict dominant behavior, but did predict quarrelsome behavior, and this link was potentiated by narcissism. Furthermore, the link between others' dominance and one's own quarrelsome behavior was mediated by negative affect. Moderated mediation was also found: Narcissism amplified the link between ratings of others' dominance and one's own quarrelsomeness and negative affect. Narcissism did not moderate the link between other dominance and own dominance, nor the link between other affiliation and own affiliation. These results suggest that narcissism is associated with specific interpersonal and affective processes, such that sensitivity to others' dominance triggers antagonistic behavior in daily life. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T
2015-01-01
Inflorescences of a dominant mutant of Arabidopsis Aux/IAA7, axr2, showed negative phototropism with a similar fluence response curve to the positive phototropism of wild-type stems. Application of a synthetic auxin, NAA, and an inhibitor of polar auxin transport, NPA, increased and decreased respectively the magnitude of the phototropic response in the wild type, while in axr2 application of NAA reduced the negative phototropic response and NPA had no effect. Decapitation of the apex induced a small negative phototropism in wild-type stems, and had no effect in axr2 plants. Inflorescences of the double mutants of auxin transporters, pgp1 pgp19, showed no phototropic response, while decapitation resulted in a negative phototropic response. These results suggest that negative phototropism can occur when the level of auxin or of auxin signaling is reduced to a minimal level, and that in plant axial organs the default phototropic response to unilateral blue light may be negative. Expression of axr2 protein by an endodermis-specific promoter resulted in agravitropism of inflorescences in a similar way to that of axr2, but phototropism was normal, confirming that the endodermis does not play a critical role in phototropism.
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Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T.
2015-01-01
Inflorescences of a dominant mutant of Arabidopsis Aux/IAA7, axr2, showed negative phototropism with a similar fluence response curve to the positive phototropism of wild-type stems. Application of a synthetic auxin, NAA, and an inhibitor of polar auxin transport, NPA, increased and decreased respectively the magnitude of the phototropic response in the wild type, while in axr2 application of NAA reduced the negative phototropic response and NPA had no effect. Decapitation of the apex induced a small negative phototropism in wild-type stems, and had no effect in axr2 plants. Inflorescences of the double mutants of auxin transporters, pgp1 pgp19, showed no phototropic response, while decapitation resulted in a negative phototropic response. These results suggest that negative phototropism can occur when the level of auxin or of auxin signaling is reduced to a minimal level, and that in plant axial organs the default phototropic response to unilateral blue light may be negative. Expression of axr2 protein by an endodermis-specific promoter resulted in agravitropism of inflorescences in a similar way to that of axr2, but phototropism was normal, confirming that the endodermis does not play a critical role in phototropism. PMID:25738325
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Barmashenko, Gleb; Buttgereit, Jens; Herring, Neil; Bader, Michael; Özcelik, Cemil; Manahan-Vaughan, Denise; Braunewell, Karl H.
2014-01-01
The second messenger cyclic GMP affects synaptic transmission and modulates synaptic plasticity and certain types of learning and memory processes. The impact of the natriuretic peptide receptor B (NPR-B) and its ligand C-type natriuretic peptide (CNP), one of several cGMP producing signaling systems, on hippocampal synaptic plasticity and learning is, however, less well understood. We have previously shown that the NPR-B ligand CNP increases the magnitude of long-term depression (LTD) in hippocampal area CA1, while reducing the induction of long-term potentiation (LTP). We have extended this line of research to show that bidirectional plasticity is affected in the opposite way in rats expressing a dominant-negative mutant of NPR-B (NSE-NPR-BΔKC) lacking the intracellular guanylyl cyclase domain under control of a promoter for neuron-specific enolase. The brain cells of these transgenic rats express functional dimers of the NPR-B receptor containing the dominant-negative NPR-BΔKC mutant, and therefore show decreased CNP-stimulated cGMP-production in brain membranes. The NPR-B transgenic rats display enhanced LTP but reduced LTD in hippocampal slices. When the frequency-dependence of synaptic modification to afferent stimulation in the range of 1–100 Hz was assessed in transgenic rats, the threshold for both, LTP and LTD induction, was shifted to lower frequencies. In parallel, NPR-BΔKC rats exhibited an enhancement in exploratory and learning behavior. These results indicate that bidirectional plasticity and learning and memory mechanism are affected in transgenic rats expressing a dominant-negative mutant of NPR-B. Our data substantiate the hypothesis that NPR-B-dependent cGMP signaling has a modulatory role for synaptic information storage and learning. PMID:25520616
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Alto, Laura Taylor; Chen, Xi; Ruhn, Kelly A; Treviño, Isaac; Tansey, Malú G
2014-01-01
CNS inflammation is a hallmark of neurodegenerative disease, and recent studies suggest that the inflammatory response may contribute to neuronal demise. In particular, increased tumor necrosis factor (TNF) signaling is implicated in the pathology of both Parkinson's disease (PD) and Alzheimer's disease (AD). We have previously shown that localized gene delivery of dominant negative TNF to the degenerating brain region can limit pathology in animal models of PD and AD. TNF is upregulated in Huntington's disease (HD), like in PD and AD, but it is unknown whether TNF signaling contributes to neuronal degeneration in HD. We used in vivo gene delivery to test whether selective reduction of soluble TNF signaling could attenuate medium spiny neuron (MSN) degeneration in the YAC128 transgenic (TG) mouse model of Huntington's disease (HD). AAV vectors encoding cDNA for dominant-negative tumor necrosis factor (DN-TNF) or GFP (control) were injected into the striatum of young adult wild type WT and YAC128 TG mice and achieved 30-50% target coverage. Expression of dominant negative TNF protein was confirmed immunohistologically and biochemically and was maintained as mice aged to one year, but declined significantly over time. However, the extent of striatal DN-TNF gene transfer achieved in our studies was not sufficient to achieve robust effects on neuroinflammation, rescue degenerating MSNs or improve motor function in treated mice. Our findings suggest that alternative drug delivery strategies should be explored to determine whether greater target coverage by DN-TNF protein might afford some level of neuroprotection against HD-like pathology and/or that soluble TNF signaling may not be the primary driver of striatal neuroinflammation and MSN loss in YAC128 TG mice.
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Counterspace Operations for Information Dominance
1999-03-01
INTERNET DOCUMENT INFORMATION FORM A. Report Title: Counterspace perations for Information Dominance B. DATE Report Downloaded From the Internet 3/10...Representative for resolution. Counterspace perations for Information Dominance by James G. Lee INTRODUCTION The Problem The launch of the Soviet...information gap between friendly and enemy forces. This positive information gap has been referred to as information dominance . Information Dominance The
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Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people.
Husebye, E; Skar, V; Høverstad, T; Melby, K
1992-01-01
Fifteen healthy old people mean age 84 years (range 80-91 years), were examined to assess the effect of advanced age on the microecology of the upper gastrointestinal tract. Twelve of 15 (80%) were hypochlorhydric with pH 6.6 (0.3) (mean (SEM) and a mean bacterial count of 10(8) colony forming units (CFU) per ml (range 10(5)-10(10)) in fasting gastric aspirate. Normochlorhydric subjects had low counts (< or = 10(1) CFU/ml). The microbial flora was dominated by viridans streptococci, coagulase negative staphylococci, and Haemophilus sp. Only one subject harboured significant concentrations of Gram negative bacilli with Escherichia coli (10(4-5) CFU/ml) and Klebsiella (10(4-5)). Strict anaerobes were not found. The total concentration of short chain fatty acids in gastric aspirate was 10.6 (2.9) mmol/l (mean (SEM). Absence of significant, intraluminal fermentation of xylose to CO2 was shown by the 14C-d Xylose breath test, and ambulatory manometry showed preserved fasting motility pattern of the small intestine. Serum immunoglobulins were normal. Advanced age is accompanied by fasting hypochlorhydria and colonisation with mainly Gram positive flora in the upper gut. Other factors than old age and fasting hypochlorhydria are required for colonisation with Gram negative bacilli. PMID:1446855
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Ito, Takuto; Kawazu, Hidetaka; Murata, Takayuki; Iwata, Seiko; Arakawa, Saki; Sato, Yoshitaka; Kuzushima, Kiyotaka; Goshima, Fumi; Kimura, Hiroshi
2014-08-01
Epstein-Barr virus (EBV) predominantly infects B cells and causes B-cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK-cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV-positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV-encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV-negative cells using the cells conditionally expressing LMP1, and on CAEBV-derived EBV-positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV-negative cell line. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lutz, Brian D; Bernhardt, Emily; Roberts, Brian
Although regional and global models of nitrogen (N) cycling typically focus on nitrate, dissolved organic nitrogen (DON) is the dominant form of nitrogen export from many watersheds and thus the dominant form of dissolved N in many streams. Our understanding of the processes controlling DON export from temperate forests is poor. In pristine systems, where biological N limitation is common, N contained in recalcitrant organic matter (OM) can dominate watershed N losses. This recalcitrant OM often has moderately constrained carbon:nitrogen (C:N) molar ratios ({approx}25-55) and therefore, greater DON losses should be observed in sites where there is greater total dissolvedmore » organic carbon (DOC) loss. In regions where anthropogenic N pollution is high, it has been suggested that increased inorganic N availability can reduce biological demand for organic N and therefore increase watershed DON losses. This would result in a positive correlation between inorganic and organic N concentrations across sites with varying N availability. In four repeated synoptic surveys of stream water chemistry from forested watersheds along an N loading gradient in the southern Appalachians, we found surprisingly little correlation between DON and DOC concentrations. Further, we found that DON concentrations were always significantly correlated with watershed N loading and stream water [NO{sub 3}{sup -}] but that the direction of this relationship was negative in three of the four surveys. The C:N molar ratio of dissolved organic matter (DOM) in streams draining watersheds with high N deposition was very high relative to other freshwaters. This finding, together with results from bioavailability assays in which we directly manipulated C and N availabilities, suggests that heterotrophic demand for labile C can increase as a result of dissolved inorganic N (DIN) loading, and that heterotrophs can preferentially remove N-rich molecules from DOM. These results are inconsistent with the two prevailing hypotheses that dominate interpretations of watershed DON loss. Therefore, we propose a new hypothesis, the indirect carbon control hypothesis, which recognizes that heterotrophic demand for N-rich DOM can keep stream water DON concentrations low when N is not limiting and heterotrophic demand for labile C is high.« less
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Rafiq, Muhammad; Hayat, Muhammad; Anesio, Alexandre M; Jamil, Syed Umair Ullah; Hassan, Noor; Shah, Aamer Ali; Hasan, Fariha
2017-01-01
Cultureable bacterial diversity of previously unexplored Siachen glacier, Pakistan, was studied. Out of 50 isolates 33 (66%) were Gram negative and 17 (34%) Gram positive. About half of the isolates were pigment producers and were able to grow at 4-37°C. 16S rRNA gene sequences revealed Gram negative bacteria dominated by Proteobacteria (especially γ-proteobacteria and β-proteobacteria) and Flavobacteria. The genus Pseudomonas (51.51%, 17) was dominant among γ- proteobacteria. β-proteobacteria constituted 4 (12.12%) Alcaligenes and 4 (12.12%) Janthinobacterium strains. Among Gram positive bacteria, phylum Actinobacteria, Rhodococcus (23.52%, 4) and Arthrobacter (23.52%, 4) were the dominating genra. Other bacteria belonged to Phylum Firmicutes with representative genus Carnobacterium (11.76%, 2) and 4 isolates represented 4 genera Bacillus, Lysinibacillus, Staphylococcus and Planomicrobium. Most of the Gram negative bacteria were moderate halophiles, while most of the Gram positives were extreme halophiles and were able to grow up to 6.12 M of NaCl. More than 2/3 of the isolates showed antimicrobial activity against multidrug resistant S. aureus, E. coli, Klebsiella pneumonia, Enterococcus faecium, Candida albicans, Aspergillus flavus and Aspergillus fumigatus and ATCC strains. Gram positive bacteria (94.11%) were more resistant to heavy metals as compared to Gram negative (78.79%) and showed maximum tolerance against iron and least tolerance against mercury.
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Rafiq, Muhammad; Hayat, Muhammad; Anesio, Alexandre M.; Jamil, Syed Umair Ullah; Hassan, Noor; Shah, Aamer Ali
2017-01-01
Cultureable bacterial diversity of previously unexplored Siachen glacier, Pakistan, was studied. Out of 50 isolates 33 (66%) were Gram negative and 17 (34%) Gram positive. About half of the isolates were pigment producers and were able to grow at 4–37°C. 16S rRNA gene sequences revealed Gram negative bacteria dominated by Proteobacteria (especially γ-proteobacteria and β-proteobacteria) and Flavobacteria. The genus Pseudomonas (51.51%, 17) was dominant among γ- proteobacteria. β-proteobacteria constituted 4 (12.12%) Alcaligenes and 4 (12.12%) Janthinobacterium strains. Among Gram positive bacteria, phylum Actinobacteria, Rhodococcus (23.52%, 4) and Arthrobacter (23.52%, 4) were the dominating genra. Other bacteria belonged to Phylum Firmicutes with representative genus Carnobacterium (11.76%, 2) and 4 isolates represented 4 genera Bacillus, Lysinibacillus, Staphylococcus and Planomicrobium. Most of the Gram negative bacteria were moderate halophiles, while most of the Gram positives were extreme halophiles and were able to grow up to 6.12 M of NaCl. More than 2/3 of the isolates showed antimicrobial activity against multidrug resistant S. aureus, E. coli, Klebsiella pneumonia, Enterococcus faecium, Candida albicans, Aspergillus flavus and Aspergillus fumigatus and ATCC strains. Gram positive bacteria (94.11%) were more resistant to heavy metals as compared to Gram negative (78.79%) and showed maximum tolerance against iron and least tolerance against mercury. PMID:28746396
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Echo Chambers: Emotional Contagion and Group Polarization on Facebook
NASA Astrophysics Data System (ADS)
Del Vicario, Michela; Vivaldo, Gianna; Bessi, Alessandro; Zollo, Fabiana; Scala, Antonio; Caldarelli, Guido; Quattrociocchi, Walter
2016-12-01
Recent findings showed that users on Facebook tend to select information that adhere to their system of beliefs and to form polarized groups - i.e., echo chambers. Such a tendency dominates information cascades and might affect public debates on social relevant issues. In this work we explore the structural evolution of communities of interest by accounting for users emotions and engagement. Focusing on the Facebook pages reporting on scientific and conspiracy content, we characterize the evolution of the size of the two communities by fitting daily resolution data with three growth models - i.e. the Gompertz model, the Logistic model, and the Log-logistic model. Although all the models appropriately describe the data structure, the Logistic one shows the best fit. Then, we explore the interplay between emotional state and engagement of users in the group dynamics. Our findings show that communities’ emotional behavior is affected by the users’ involvement inside the echo chamber. Indeed, to an higher involvement corresponds a more negative approach. Moreover, we observe that, on average, more active users show a faster shift towards the negativity than less active ones.
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Rainfall-aerosol relationships explained by wet scavenging and humidity
NASA Astrophysics Data System (ADS)
Grandey, Benjamin S.; Gururaj, Anisha; Stier, Philip; Wagner, Till M.
2014-08-01
Relationships between precipitation rate and aerosol optical depth, the extinction of light by aerosol in an atmospheric column, have been observed in satellite-retrieved data. What are the reasons for these precipitation-aerosol relationships? We investigate relationships between convective precipitation rate (Rconv) and aerosol optical depth (τtot) using the ECHAM5-HAM aerosol-climate model. We show that negative Rconv-τtot relationships arise due to wet scavenging of aerosol. The apparent lack of negative Rconv-τtot relationships in satellite-retrieved data is likely because the satellite data do not sample wet scavenging events. When convective wet scavenging is excluded in the model, we find positive Rconv-τtot relationships in regions where convective precipitation is the dominant form of model precipitation. The spatial distribution of these relationships is in good agreement with satellite-based results. We further demonstrate that a substantial component of these positive relationships arises due to covariation with large-scale relative humidity. Although the interpretation of precipitation-aerosol relationships remains a challenging question, we suggest that progress can be made through a synergy between observations and models.
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Echo Chambers: Emotional Contagion and Group Polarization on Facebook.
Del Vicario, Michela; Vivaldo, Gianna; Bessi, Alessandro; Zollo, Fabiana; Scala, Antonio; Caldarelli, Guido; Quattrociocchi, Walter
2016-12-01
Recent findings showed that users on Facebook tend to select information that adhere to their system of beliefs and to form polarized groups - i.e., echo chambers. Such a tendency dominates information cascades and might affect public debates on social relevant issues. In this work we explore the structural evolution of communities of interest by accounting for users emotions and engagement. Focusing on the Facebook pages reporting on scientific and conspiracy content, we characterize the evolution of the size of the two communities by fitting daily resolution data with three growth models - i.e. the Gompertz model, the Logistic model, and the Log-logistic model. Although all the models appropriately describe the data structure, the Logistic one shows the best fit. Then, we explore the interplay between emotional state and engagement of users in the group dynamics. Our findings show that communities' emotional behavior is affected by the users' involvement inside the echo chamber. Indeed, to an higher involvement corresponds a more negative approach. Moreover, we observe that, on average, more active users show a faster shift towards the negativity than less active ones.
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Wagh, Ajay A.; Roan, Esra; Chapman, Kenneth E.; Desai, Leena P.; Rendon, David A.; Eckstein, Eugene C.; Waters, Christopher M.
2008-01-01
Restoration of lung homeostasis following injury requires efficient wound healing by the epithelium. The mechanisms of lung epithelial wound healing include cell spreading and migration into the wounded area and later cell proliferation. We hypothesized that mechanical properties of cells vary near the wound edge, and this may provide cues to direct cell migration. To investigate this hypothesis, we measured variations in the stiffness of migrating human bronchial epithelial cells (16HBE cells) ∼2 h after applying a scratch wound. We used atomic force microscopy (AFM) in contact mode to measure the cell stiffness in 1.5-μm square regions at different locations relative to the wound edge. In regions far from the wound edge (>2.75 mm), there was substantial variation in the elastic modulus in specific cellular regions, but the median values measured from multiple fields were consistently lower than 5 kPa. At the wound edge, cell stiffness was significantly lower within the first 5 μm but increased significantly between 10 and 15 μm before decreasing again below the median values away from the wound edge. When cells were infected with an adenovirus expressing a dominant negative form of RhoA, cell stiffness was significantly decreased compared with cells infected with a control adenovirus. In addition, expression of dominant negative RhoA abrogated the peak increase in stiffness near the wound edge. These results suggest that cells near the wound edge undergo localized changes in cellular stiffness that may provide signals for cell spreading and migration. PMID:18487359
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Takahashi-Tezuka, Mariko; Yoshida, Yuichi; Fukada, Toshiyuki; Ohtani, Takuya; Yamanaka, Yojiro; Nishida, Keigo; Nakajima, Koichi; Hibi, Masahiko; Hirano, Toshio
1998-01-01
Gab1 has structural similarities with Drosophila DOS (daughter of sevenless), which is a substrate of the protein tyrosine phosphatase Corkscrew. Both Gab1 and DOS have a pleckstrin homology domain and tyrosine residues, potential binding sites for various SH2 domain-containing adapter molecules when they are phosphorylated. We found that Gab1 was tyrosine phosphorylated in response to various cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN-α), and IFN-γ. Upon the stimulation of IL-6 or IL-3, Gab1 was found to form a complex with phosphatidylinositol (PI)-3 kinase and SHP-2, a homolog of Corkscrew. Mutational analysis of gp130, the common subunit of IL-6 family cytokine receptors, revealed that neither tyrosine residues of gp130 nor its carboxy terminus was required for tyrosine phosphorylation of Gab1. Expression of Gab1 enhanced gp130-dependent mitogen-activated protein (MAP) kinase ERK2 activation. A mutation of tyrosine 759, the SHP-2 binding site of gp130, abrogated the interactions of Gab1 with SHP-2 and PI-3 kinase as well as ERK2 activation. Furthermore, ERK2 activation was inhibited by a dominant negative p85 PI-3 kinase, wortmannin, or a dominant negative Ras. These observations suggest that Gab1 acts as an adapter molecule in transmitting signals to ERK MAP kinase for the cytokine receptor gp130 and that SHP-2, PI-3 kinase, and Ras are involved in Gab1-mediated ERK activation. PMID:9632795
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Src promotes delta opioid receptor (DOR) desensitization by interfering with receptor recycling.
Archer-Lahlou, Elodie; Audet, Nicolas; Amraei, Mohammad Gholi; Huard, Karine; Paquin-Gobeil, Mélanie; Pineyro, Graciela
2009-01-01
Abstract An important limitation in the clinical use of opiates is progressive loss of analgesic efficacy over time. Development of analgesic tolerance is tightly linked to receptor desensitization. In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the membrane. In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. A first series of experiments demonstrated that agonist binding activates Src and destabilizes a constitutive complex formed by the spontaneous association of DORs with the kinase. Src contribution to DOR desensitization was then established by showing that pre-treatment with Src inhibitor PP2 (20 microM; 1 hr) or transfection of a dominant negative Src mutant preserved DOR signalling following sustained exposure to an agonist. This protection was afforded without interfering with endocytosis, but suboptimal internalization interfered with PP2 ability to preserve DOR signalling, suggesting a post-endocytic site of action for the kinase. This assumption was confirmed by demonstrating that Src inhibition by PP2 or its silencing by siRNA increased membrane recovery of internalized DORs and was further corroborated by showing that inhibition of recycling by monensin or dominant negative Rab11 (Rab11S25N) abolished the ability of Src blockers to prevent desensitization. Finally, Src inhibitors accelerated recovery of DOR-Galphal3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors.
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From Design for Dominance to Design for Dialogue
ERIC Educational Resources Information Center
Keitges, Mark J.
2012-01-01
The increasing complexity of the network society is the result of a particular approach to design: that of mastery, control, ease of use and interconnectedness. The author analyzes this design approach for its negative and positive aspects, which he labels as "designing for dominance" and "designing for dialogue", respectively. Both of these…
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Miranda T. Curzon; Anthony W. D' Amato; Brian J. Palik; Kris Verheyen
2016-01-01
Questions: Does the increase in disturbance associated with removing harvest residues negatively impact biodiversity and resilience in aspen-dominated forest ecosystems? How do responses of functional diversity measures relate to community recovery and standing biomass? Location: Aspen (Populus tremuloides, Michx.) mixedwood forests in Minnesota...
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Negative Effects of Makeup Use on Perceptions of Leadership Ability Across Two Ethnicities.
James, Esther A; Jenkins, Shauny; Watkins, Christopher D
2018-01-01
Cosmetics alter social perceptions, and prior work suggests that cosmetic use may aid female intrasexual competition, making women appear more dominant to other women but more prestigious to other men. It is unclear whether these findings reflect general improvements in perceptions of traits related to women's dominance or if they are specific to mating contexts only. Here, across two ethnicities, we examined effects of cosmetics used for a social night out on perceptions of women's leadership ability, a trait that denotes competence/high status outside of mating contexts. Participants of African and Caucasian ethnicity judged faces for leadership ability where half of the trials differed in ethnicity (own- vs. other-ethnicity face pairs) and the subtlety of the color manipulation (50% vs. 100%). Regardless of the participant's sex or ethnicity, makeup used for a social night out had a negative effect on perceptions of women's leadership ability. Our findings suggest that, in prior work, women are afforded traits related to dominance, as makeup enhances perceptions of traits that are important for successful female mating competition but not other components of social dominance such as leadership.
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Gomez-Hurtado, Nieves; Boczek, Nicole J.; Kryshtal, Dmytro O.; Johnson, Christopher N.; Sun, Jennifer; Nitu, Florentin R.; Cornea, Razvan L.; Chazin, Walter J.; Calvert, Melissa L.; Tester, David J.; Ackerman, Michael J.; Knollmann, Bjorn C.
2016-01-01
Background Calmodulin (CaM) mutations are associated with severe forms of long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). We recently reported that CaM mutations were found in 13% of genotype-negative LQTS patients, but the prevalence of CaM mutations in genotype-negative CPVT patients is unknown. Here, we identify and characterize CaM mutations in 12 patients with genotype-negative but clinically-diagnosed CPVT. Methods and Results Mutational analysis of CALM1, CALM2 and CALM3 coding regions, in vitro measurement of CaM-Ca2+ (Ca) binding affinity, RyR2-CaM binding, Ca handling, L-type Ca current (LTCC) and action potential duration (APD). We identified a novel CaM mutation – A103V – in CALM3 in 1 of 12 patients (8%), a female who experienced episodes of exertion-induced syncope since age 10, had normal QT interval, and displayed ventricular ectopy during stress testing consistent with CPVT. A103V modestly lowered CaM Ca-binding affinity (3-fold reduction vs WT-CaM), but did not alter CaM binding to RyR2. In permeabilized cardiomyocytes, A103V-CaM (100 nM) promoted spontaneous Ca wave and spark activity, a cellular phenotype of RyR2 activation. Even a 1:3 mixture of A103V-CaM:WT-CaM activated Ca waves, demonstrating functional dominance. Compared to LQTS D96V-CaM, A103V-CaM had significantly less effects on LTCC inactivation and APD, and caused delayed after depolarizations (DADs) and triggered beats in intact cardiomyocytes. Conclusions We discovered a novel CPVT mutation in the CALM3 gene that shares functional characteristics with established CPVT-associated mutations in CALM1. A small proportion of A103V-CaM is sufficient to evoke arrhythmogenic Ca disturbances via RyR2 dysregulation, which explains the autosomal dominant inheritance. PMID:27516456
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Chemically cued suppression of coral reef resilience: Where is the tipping point?
NASA Astrophysics Data System (ADS)
Brooker, Rohan M.; Hay, Mark E.; Dixson, Danielle L.
2016-12-01
Coral reefs worldwide are shifting from high-diversity, coral-dominated communities to low-diversity systems dominated by seaweeds. This shift can impact essential recovery processes such as larval recruitment and ecosystem resilience. Recent evidence suggests that chemical cues from certain corals attract, and from certain seaweeds suppress, recruitment of juvenile fishes, with loss of coral cover and increases in seaweed cover creating negative feedbacks that prevent reef recovery and sustain seaweed dominance. Unfortunately, the level of seaweed increase and coral decline that creates this chemically cued tipping point remains unknown, depriving managers of data-based targets to prevent damaging feedbacks. We conducted flume and field assays that suggest juvenile fishes sense and respond to cues produced by low levels of seaweed cover. However, the herbivore species we tested was more tolerant of degraded reef cues than non-herbivores, possibly providing some degree of resilience if these fishes recruit, consume macroalgae, and diminish negative cues.
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Freeman, Dan; Aquino, Karl; McFerran, Brent
2009-01-01
Three studies examined the relationship between social dominance orientation (SDO), the experience of moral elevation, and Whites' donations to charitable organizations. Study 1 used video clips depicting acts of moral excellence to elicit a state of moral elevation (a distinctive feeling of warmth and expansion, which is accompanied by admiration, affection, and even love for people whose exemplary moral behavior is being observed). Results show that moral elevation increased participants' willingness to donate to a Black-oriented charity and attenuated the negative effect of the group-based dominance (GBD) component of SDO on donation behavior. Studies 2 and 3 replicate and extend these findings by using a written story to elicit a state of moral elevation and examining actual donations to a Black-oriented charity. Results show that moral elevation increased donations to the Black-oriented charity and neutralized the negative influence of GBD.
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On the Dominance of Attitude Emotionality.
Rocklage, Matthew D; Fazio, Russell H
2016-02-01
Many situations in our lives require us to make relatively quick decisions as whether to approach or avoid a person or object, buy or pass on a product, or accept or reject an offer. These decisions are particularly difficult when there are both positive and negative aspects to the object. How do people go about navigating this conflict to come to a summary judgment? Using the Evaluative Lexicon (EL), we demonstrate across three studies, 7,700 attitude expressions, and nearly 50 different attitude objects that when positivity and negativity conflict, the valence that is based more on emotion is more likely to dominate. Furthermore, individuals are also more consistent in the expression of their univalent summary judgments when they involve greater emotionality. In sum, valence that is based on emotion tends to dominate when resolving ambivalence and also helps individuals to remain consistent when offering quick judgments. © 2015 by the Society for Personality and Social Psychology, Inc.
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Regulation of HTLV-1 Gag budding by Vps4A, Vps4B, and AIP1/Alix
Urata, Shuzo; Yokosawa, Hideyoshi; Yasuda, Jiro
2007-01-01
Background HTLV-1 Gag protein is a matrix protein that contains the PTAP and PPPY sequences as L-domain motifs and which can be released from mammalian cells in the form of virus-like particles (VLPs). The cellular factors Tsg101 and Nedd4.1 interact with PTAP and PPPY, respectively, within the HTLV-1 Gag polyprotein. Tsg101 forms a complex with Vps28 and Vps37 (ESCRT-I complex) and plays an important role in the class E Vps pathway, which mediates protein sorting and invagination of vesicles into multivesicular bodies. Nedd4.1 is an E3 ubiquitin ligase that binds to the PPPY motif through its WW motif, but its function is still unknown. In the present study, to investigate the mechanism of HTLV-1 budding in detail, we analyzed HTLV-1 budding using dominant negative (DN) forms of the class E proteins. Results Here, we report that DN forms of Vps4A, Vps4B, and AIP1 inhibit HTLV-1 budding. Conclusion These findings suggest that HTLV-1 budding utilizes the MVB pathway and that these class E proteins may be targets for prevention of mother-to-infant vertical transmission of the virus. PMID:17601348
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Li, Dien; Kaplan, Daniel I; Roberts, Kimberly A; Seaman, John C
2012-03-06
Cementitious materials are increasingly used as engineered barriers and waste forms for radiological waste disposal. Yet their potential effect on mobile colloid generation is not well-known, especially as it may influence colloid-facilitated contaminant transport. Whereas previous papers have studied the introduction of cement colloids into sediments, this study examined the influence of cement leachate chemistry on the mobilization of colloids from a subsurface sediment collected from the Savannah River Site, USA. A sharp mobile colloid plume formed with the introduction of a cement leachate simulant. Colloid concentrations decreased to background concentrations even though the aqueous chemical conditions (pH and ionic strength) remained unchanged. Mobile colloids were mainly goethite and to a lesser extent kaolinite. The released colloids had negative surface charges and the mean particle sizes ranged primarily from 200 to 470 nm. Inherent mineralogical electrostatic forces appeared to be the controlling colloid removal mechanism in this system. In the background pH of ~6.0, goethite had a positive surface charge, whereas quartz (the dominant mineral in the immobile sediment) and kaolinite had negative surface charges. Goethite acted as a cementing agent, holding kaolinite and itself onto the quartz surfaces due to the electrostatic attraction. Once the pH of the system was elevated, as in the cementitious high pH plume front, the goethite reversed to a negative charge, along with quartz and kaolinite, then goethite and kaolinite colloids were mobilized and a sharp spike in turbidity was observed. Simulating conditions away from the cementitious source, essentially no colloids were mobilized at 1:1000 dilution of the cement leachate or when the leachate pH was ≤ 8. Extreme alkaline pH environments of cementitious leachate may change mineral surface charges, temporarily promoting the formation of mobile colloids.
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Playing the Fertility Game at Work: An Equilibrium Model of Peer Effects.
Ciliberto, Federico; Miller, Amalia R; Nielsen, Helena Skyt; Simonsen, Marianne
2016-08-01
We study workplace peer effects in fertility decisions using a game theory model of strategic interactions among coworkers that allows for multiple equilibria. Using register-based data on fertile-aged women working in medium sized establishments in Denmark, we uncover negative average peer effects. Allowing for heterogeneous effects by worker type, we find that positive effects dominate across worker types defined by age or education. Negative effects dominate within age groups and among low-education types. Policy simulations show that these estimated effects make the distribution of where women work an important consideration, beyond simply if they work, in predicting population fertility.
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Playing the Fertility Game at Work: An Equilibrium Model of Peer Effects
Ciliberto, Federico; Miller, Amalia R.; Nielsen, Helena Skyt; Simonsen, Marianne
2016-01-01
We study workplace peer effects in fertility decisions using a game theory model of strategic interactions among coworkers that allows for multiple equilibria. Using register-based data on fertile-aged women working in medium sized establishments in Denmark, we uncover negative average peer effects. Allowing for heterogeneous effects by worker type, we find that positive effects dominate across worker types defined by age or education. Negative effects dominate within age groups and among low-education types. Policy simulations show that these estimated effects make the distribution of where women work an important consideration, beyond simply if they work, in predicting population fertility. PMID:27605729
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Al-Hendy, Ayman; Lee, Eun J; Wang, Hui Q; Copland, John A
2004-11-01
Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management. This study was undertaken to investigate a potential therapy for leiomyoma; we used a mutated dominant-negative estrogen receptor gene delivered via an adenoviral vector (Ad-ER-DN). Ad-ER-DN transduction, in both human and rat leiomyoma cell lines, induced an increase in both caspase-3 levels and BAX/Bcl-2 ratio with evident apoptosis in the TdT-mediated dUTP nick-end labeling assay. In nude mice, rat leiomyoma cells ex vivo transduced with Ad-ER-DN supported significantly smaller tumors compared with Ad-LacZ-treated cells 5 weeks after implantation. In mice treated by direct intratumor injection into preexisting lesions, Ad-ER-DN caused immediate overall arrest of tumor growth. The Ad-ER-DN-treated tumors demonstrated severely inhibited cell proliferation (BrdU index) and a marked increase in the number of apoptotic cells (TdT-mediated dUTP nick-end labeling index). Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.
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CRISPR-mediated targeting of HER2 inhibits cell proliferation through a dominant negative mutation.
Wang, Huajing; Sun, William
2017-01-28
With the discovery of the CRISPR/Cas9 technology, genome editing could be performed in a rapid, precise and effective manner. Its potential applications in functional interrogation of cancer-causing genes and cancer therapy have been extensively explored. In this study, we demonstrated the use of the CRISPR/Cas9 system to directly target the oncogene HER2. Directing Cas9 to exons of the HER2 gene inhibited cell growth in breast cancer cell lines that harbor amplification of the HER2 locus. The inhibitory effect was potentiated with the addition of PARP inhibitors. Unexpectedly, CRISPR-induced mutations did not significantly affect the level of HER2 protein expression. Instead, CRISPR targeting appeared to exert its effect through a dominant negative mutation. This HER2 mutant interfered with the MAPK/ERK axis of HER2 downstream signaling. Our work provides a novel mechanism underlying the anti-cancer effects of HER2-targeting by CRISPR/Cas9, which is distinct from the clinical drug Herceptin. In addition, it opens up the possibility that incomplete CRISPR targeting of certain oncogenes could still have therapeutic value by generation of dominant negative mutants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Akhrameyeva, Natalie V.; Zhang, Pengwei; Sugiyama, Nao; Behar, Samuel M.; Yao, Feng
2011-01-01
Using the T-REx (Invitrogen, California) gene switch technology and a dominant-negative mutant polypeptide of herpes simplex virus 1 (HSV-1)-origin binding protein UL9, we previously constructed a glycoprotein D-expressing replication-defective and dominant-negative HSV-1 recombinant viral vaccine, CJ9-gD, for protection against HSV infection and disease. It was demonstrated that CJ9-gD is avirulent following intracerebral inoculation in mice, cannot establish detectable latent infection following different routes of infection, and offers highly effective protective immunity against primary HSV-1 and HSV-2 infection and disease in mouse and guinea pig models of HSV infections. Given these favorable safety and immunological profiles of CJ9-gD, aiming to maximize levels of HSV-2 glycoprotein D (gD2) expression, we have constructed an ICP0 null mutant-based dominant-negative and replication-defective HSV-2 recombinant, CJ2-gD2, that contains 2 copies of the gD2 gene driven by the tetracycline operator (tetO)-bearing HSV-1 major immediate-early ICP4 promoter. CJ2-gD2 expresses gD2 as efficiently as wild-type HSV-2 infection and can lead to a 150-fold reduction in wild-type HSV-2 viral replication in cells coinfected with CJ2-gD2 and wild-type HSV-2 at the same multiplicity of infection. CJ2-gD2 is avirulent following intracerebral injection and cannot establish a detectable latent infection following subcutaneous (s.c.) immunization. CJ2-gD2 is a more effective vaccine than HSV-1 CJ9-gD and a non-gD2-expressing dominant-negative and replication-defective HSV-2 recombinant in protection against wild-type HSV-2 genital disease. Using recall response, we showed that immunization with CJ2-gD2 elicited strong HSV-2-specific memory CD4+ and CD8+ T-cell responses. Collectively, given the demonstrated preclinical immunogenicity and its unique safety profiles, CJ2-gD2 represents a new class of HSV-2 replication-defective recombinant viral vaccines in protection against HSV-2 genital infection and disease. PMID:21389121
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Akt2-Dependent Phosphorylation of Radixin in Regulation of Mrp-2 Trafficking in WIF-B Cells.
Suda, Jo; Rockey, Don C; Karvar, Serhan
2016-02-01
The dominant ezrin/radixin/moesin protein in hepatocytes is radixin, which plays an important role in mediating the binding of F-actin to the plasma membrane after a conformational activation by phosphorylation at Thr564. Here we have investigated the importance of Akt-mediated radixin Thr564 phosphorylation on Mrp-2 distribution and function in WIF-B cells. Mrp-2 is an adenosine triphosphate (ATP)-binding cassette transporter that plays an important role in detoxification and chemoprotection by transporting a wide range of compounds, especially conjugates of lipophilic substances with glutathione, organic anions, and drug metabolites such as glucuronides. Akt1 and Akt2 expression were manipulated using dominant active and negative constructs as well as Akt1 and Akt2 siRNA. Cellular distribution of radixin and Mrp-2 was visualized by fluorescence microscopy. A 5-chloromethylfluorescein diacetate, which is a substrate of the Mrp-2 and is actively transported in canalicular lumina, was used to measure Mrp-2 function. Radixin phosphorylation was significantly increased in wild-type and dominant active Akt2 transfected cells. Furthermore, radixin and Mrp-2 were localized at the canalicular membrane, similar to control cells. In contrast, overexpression of dominant negative Akt2, siRNA knockdown of Akt2 and a specific Akt inhibitor prevented radixin phosphorylation and led to alteration of normal radixin and Mrp-2 localization; inhibition of Akt2, but not Akt1 function led to radixin localization to the cytoplasmic space. In addition, dominant negative and Akt2 knockdown led to a dramatically impaired hepatocyte secretory response, while wild-type and dominant active Akt2 transfected cells exhibited increased 5-chloromethylfluorescein diacetate excretion. In contrast to Akt2, Akt1 was not associated with radixin phosphorylation. These studies, therefore, identify Akt2 as a critical kinase that regulates radixin phosphorylation and leads to Mrp-2 translocation and function.
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Genetics Home Reference: autosomal dominant partial epilepsy with auditory features
... Twitter Home Health Conditions ADPEAF Autosomal dominant partial epilepsy with auditory features Printable PDF Open All Close ... the expand/collapse boxes. Description Autosomal dominant partial epilepsy with auditory features ( ADPEAF ) is an uncommon form ...
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Mposkos, Evripidis; Perraki, Maria; Palikari, Sarra
2009-08-01
Single and multiphase inclusions in garnet porphyroblasts from the diamond-bearing pelitic gneisses were studied by means of combined Raman Spectroscopy and Electron Scanning Microscopy (SEM/EDX). They are either randomly distributed or with preferred orientation within the garnet host and their dimensions vary from less than 5 up to 60 microm. In the single-phase inclusions quartz, rutile, kyanite and graphite dominate. Biotite, zircon, apatite, monazite and allanite are also common. Two types of multiphase inclusions were recognized, hydrous silicate (Type I) and silicate-carbonate (Type II) ones. The carbon-bearing multiphase inclusions predominantly consist of Mg-siderite+graphite+CO(2)+muscovite+quartz formed by a high density carboniferous fluid rich in Fe, Mg, Si and less Ca, Mn, Al and K trapped in the growing garnet in a prograde stage of metamorphism at high-pressure (HP) conditions. The carbon-free multiphase inclusions predominantly consist of biotite+quartz+rutile+/-kyanite+muscovite formed through decompression-dehydration/melting reactions of pre-existing phengite. Single and multiphase inclusions are characterized by polygonal to negative crystal shape formed by dissolution-reprecipitation mechanism between the garnet host and the inclusions during the long lasting cooling period (>100 Ma) of the Kimi Complex.
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Viscous and Thermal Effects on Hydrodynamic Instability in Liquid-Propellant Combustion
NASA Technical Reports Server (NTRS)
Margolis, Stephen B.; Sacksteder, Kurt (Technical Monitor)
2000-01-01
A pulsating form of hydrodynamic instability has recently been shown to arise during the deflagration of liquid propellants in those parameter regimes where the pressure-dependent burning rate is characterized by a negative pressure sensitivity. This type of instability can coexist with the classical cellular, or Landau, form of hydrodynamic instability, with the occurrence of either dependent on whether the pressure sensitivity is sufficiently large or small in magnitude. For the inviscid problem, it has been shown that when the burning rate is realistically allowed to depend on temperature as well as pressure, that sufficiently large values of the temperature sensitivity relative to the pressure sensitivity causes the pulsating form of hydrodynamic instability to become dominant. In that regime, steady, planar burning becomes intrinsically unstable to pulsating disturbances whose wavenumbers are sufficiently small. In the present work, this analysis is extended to the fully viscous case, where it is shown that although viscosity is stabilizing for intermediate and larger wavenumber perturbations, the intrinsic pulsating instability for small wavenumbers remains. Under these conditions, liquid-propellant combustion is predicted to be characterized by large unsteady cells along the liquid/gas interface.
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Dedifferentiation rescues senescence of progeria cells but only while pluripotent.
Niedernhofer, Laura J; Glorioso, Joseph C; Robbins, Paul D
2011-06-01
Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disease in which children develop pathologies associated with old age. HGPS is caused by a mutation in the LMNA gene, resulting in the formation of a dominant negative form of the intermediate filament, nuclear structural protein lamin A, termed progerin. Expression of progerin alters the nuclear architecture and heterochromatin, affecting cell cycle progression and genomic stability. Two groups recently reported the successful generation and characterization of induced pluripotent stem cells (iPSCs) from HGPS fibroblasts. Remarkably, progerin expression and senescence phenotypes are lost in iPSCs but not in differentiated progeny. These new HGPS iPSCs are valuable for characterizing the role of progerin in driving HGPS and aging and for screening therapeutic strategies to prevent or delay cell senescence.
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Mutations in the C-terminal fragment of DnaK affecting peptide binding.
Burkholder, W F; Zhao, X; Zhu, X; Hendrickson, W A; Gragerov, A; Gottesman, M E
1996-01-01
Escherichia coli DnaK acts as a molecular chaperone through its ATP-regulated binding and release of polypeptide substrates. Overexpressing a C-terminal fragment (CTF) of DnaK (Gly-384 to Lys-638) containing the polypeptide substrate binding domain is lethal in wild-type E. coli. This dominant-negative phenotype may result from the nonproductive binding of CTF to cellular polypeptide targets of DnaK. Mutations affecting DnaK substrate binding were identified by selecting noncytotoxic CTF mutants followed by in vitro screening. The clustering of such mutations in the three-dimensional structure of CTF suggests the model that loops L1,2 and L4,5 form a rigid core structure critical for interactions with substrate. Images Fig. 1 Fig. 2 Fig. 3 PMID:8855230
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c-rel activates but v-rel suppresses transcription from kappa B sites.
Inoue, J; Kerr, L D; Ransone, L J; Bengal, E; Hunter, T; Verma, I M
1991-01-01
We show that the product of the protooncogene c-rel is a constituent of an NF-kappa B-like complex that binds to the kappa B site originally identified in the enhancer of immunoglobulin kappa light chain gene. c-rel protein synthesized in bacteria binds to the kappa B site in a sequence-specific manner. The rel-kappa B complex can be disrupted by incubation with anti-rel antibodies. The rel protein can form oligomers. The c-rel protein can activate transcription from promoters containing kappa B sites; v-rel, on the other hand, suppresses the transcription of genes linked to kappa B sites. Thus, v-rel may interfere with the normal transcriptional machinery of the cell by acting as a dominant negative mutant. Images PMID:2023921
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Identity formation and social maladaptation in foster adolescents.
Yancey, A K
1992-01-01
The literature on identity formation in individuals from socially devalued racial and ethnic groups in the United States is summarized. Implications are discussed for a particular segment of at-risk adolescents--those in foster care residential group homes--who have received little published attention. The majority, in large urban centers, are African-American or Latino. These young people bear a disproportionate burden of such societal problems as unintended pregnancy and childbearing, academic underachievement and early educational discontinuation, substance abuse, and, ultimately, homelessness and more individually and socially costly forms of dependency (criminal justice, welfare, or mental health systems). It is postulated that their social maladaptation is reflective of identity disturbances created by the negative images of African-Americans and Latinos perpetuated by the dominant society and unfiltered by optimal parental racial socialization.
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ERIC Educational Resources Information Center
Irving, Miles Anthony; Hudley, Cynthia
2005-01-01
This study measured the relationship between outcome expectations, outcome value, and cultural mistrust among African American male high school students (N = 75) attending an urban, Southern California school. We hypothesized that a negative perception of the dominant culture would negatively affect academic outcome expectations and academic…
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Yasui, Takuya; Kaga, Kimitaka; Sakai, Kuniyoshi L
2009-02-01
Using magnetoencephalography (MEG), we report here the hemispheric dominance of the auditory cortex that is selectively modulated by unexpected errors in the lyrics and melody of songs (lyrics and melody deviants), thereby elucidating under which conditions the lateralization of auditory processing changes. In experiment 1 using familiar songs, we found that the dipole strength of responses to the lyrics deviants was left-dominant at 140 ms (M140), whereas that of responses to the melody deviants was right-dominant at 130 ms (M130). In experiment 2 using familiar songs with a constant syllable or pitch, the dipole strength of frequency mismatch negativity elicited by oddballs was left-dominant. There were significant main effects of experiment (1 and 2) for the peak latencies and for the coordinates of the dipoles, indicating that the M140 and M130 were not the frequency mismatch negativity. In experiment 3 using newly memorized songs, the right-dominant M130 was observed only when the presented note was unexpected one, independent of perceiving unnatural pitch transitions (i.e., perceptual saliency) and of selective attention to the melody of songs. The consistent right-dominance of the M130 between experiments 1 and 3 suggests that the M130 in experiment 1 is due to unexpected notes deviating from well-memorized songs. On the other hand, the left-dominant M140 was elicited by lyrics deviants, suggesting the influence of top-down linguistic information and the memory of the familiar songs. We thus conclude that the left- lateralized M140 and right-lateralized M130 reflect the expectation based on top-down information of language and music, respectively.
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Ata: An Indigenous Knowledge Based Pedagogical Approach to Teaching
ERIC Educational Resources Information Center
Forsyth, Huhana
2017-01-01
Western education theory and philosophy as the domain of the dominant pedagogy forms the basis of the New Zealand education system. Although the current form of education is reflective of the dominant cultures ideologies and philosophies it does not always serve the interests of all students. The philosophy of Ata offers an indigenous knowledge…
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Carnell, Paul E; Keough, Michael J
2014-05-01
Understanding the impact of multiple stressors on ecosystems is of pronounced importance, particularly when one or more of those stressors is anthropogenic. Here we investigated the role of physical disturbance and increased nutrients on reefs dominated by the canopy-forming kelp Ecklonia radiata. We combined experimental kelp canopy removals and additional nutrient at three different locations in a large embayment in temperate southeastern Australia. Over the following winter recruitment season, Ecklonia recruitment was unaffected by increased nutrients alone, but tripled at all sites where the canopy had been removed. At one site, the combination of disturbance and increased nutrients resulted in more than four times the recruitment of the introduced kelp Undaria pinnatifida. Six months after disturbance, the proliferation of the Undaria canopy in the canopy-removal and nutrient-addition treatment negatively influenced the recovery of the native kelp Ecklonia. Given the otherwise competitive dominance of adult Ecklonia, this provides a mechanism whereby Undaria could maintain open space for the following recruitment season. This interplay between disturbance, nutrients and the response of native and invasive species makes a compelling case for how a combination of factors can influence species dynamics.
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Ionospheric convection signatures observed by DE 2 during northward interplanetary magnetic field
NASA Technical Reports Server (NTRS)
Heelis, R. A.; Hanson, W. B.; Reiff, P. H.; Winningham, J. D.
1986-01-01
Observations of the ionospheric convection signature at high latitudes are examined during periods of prolonged northward interplanetary magnetic field (IMF). The data from Dynamics Explorer 2 show that a four-cell convection pattern can frequently be observed in a region that is displaced to the sunward side of the dawn-dusk meridian regardless of season. In the eclipsed ionosphere, extremely structured or turbulent flow exists with no identifiable connection to a more coherent pattern that may simultaneously exist in the dayside region. The two highest-latitude convection cells that form part of the coherent dayside pattern show a dependence on the y component of the IMF. This dependence is such that a clockwise circulating cell displaced toward dawn dominates the high-latitude region when B(Y) is positive. Anti-clockwise circulation displaced toward dusk dominates the highest latitudes when B(Y) is negative. Examination of the simultaneously observed energetic particle environment suggests that both open and closed field lines may be associated with the high-latitude convection cells. On occasions these entire cells can exist on open field lines. The existence of closed field lines in regions of sunward flow is also apparent in the data.
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ERIC Educational Resources Information Center
Friedman, Howard S.
1979-01-01
Students' perceptions of sincerity, dominance, and positivity were measured by pairing happy, angry, surprised and sad faces of teachers with teachers' comments characterized as positive or negative and dominant or submissive. Clear effects of facial-verbal combinations emerged; there were no sex differences other than in perceptions of sincerity.…
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A new method for evaluating forest thinning: growth dominance in managed Pinus resinosa stands
John B. Bradford; Anthony W. D' Amato; Brian J. Palik; Shawn Fraver
2010-01-01
Growth dominance is a relatively new, simple, quantitative metric of within-stand individual tree growth patterns, and is defined as positive when larger trees in the stand display proportionally greater growth than smaller trees, and negative when smaller trees display proportionally greater growth than larger trees. We examined long-term silvicultural experiments in...
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ERIC Educational Resources Information Center
Agnew, Shire; Sandretto, Susan
2016-01-01
When Agnew found the same, largely negative, dominant discourses of menstruation present in classroom lessons that researchers have been identifying for over 30 years, she sought different approaches to menstruation education. In this article the authors highlight the power of the media to (re)construct dominant discourses of menstruation and the…
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Cosmology with negative absolute temperatures
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vieira, J.P.P.; Byrnes, Christian T.; Lewis, Antony, E-mail: J.Pinto-Vieira@sussex.ac.uk, E-mail: ctb22@sussex.ac.uk, E-mail: antony@cosmologist.info
Negative absolute temperatures (NAT) are an exotic thermodynamical consequence of quantum physics which has been known since the 1950's (having been achieved in the lab on a number of occasions). Recently, the work of Braun et al. [1] has rekindled interest in negative temperatures and hinted at a possibility of using NAT systems in the lab as dark energy analogues. This paper goes one step further, looking into the cosmological consequences of the existence of a NAT component in the Universe. NAT-dominated expanding Universes experience a borderline phantom expansion ( w < -1) with no Big Rip, and their contractingmore » counterparts are forced to bounce after the energy density becomes sufficiently large. Both scenarios might be used to solve horizon and flatness problems analogously to standard inflation and bouncing cosmologies. We discuss the difficulties in obtaining and ending a NAT-dominated epoch, and possible ways of obtaining density perturbations with an acceptable spectrum.« less
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Mood, motivation, and misinformation: aging and affective state influences on memory.
Hess, Thomas M; Popham, Lauren E; Emery, Lisa; Elliott, Tonya
2012-01-01
Normative age differences in memory have typically been attributed to declines in basic cognitive and cortical mechanisms. The present study examined the degree to which dominant everyday affect might also be associated with age-related memory errors using the misinformation paradigm. Younger and older adults viewed a positive and a negative event, and then were exposed to misinformation about each event. Older adults exhibited a higher likelihood than young adults of falsely identifying misinformation as having occurred in the events. Consistent with expectations, strength of the misinformation effect was positively associated with dominant mood, and controlling for mood eliminated any age effects. Also, motivation to engage in complex cognitive activity was negatively associated with susceptibility to misinformation, and susceptibility was stronger for negative than for positive events. We argue that motivational processes underlie all of the observed effects, and that such processes are useful in understanding age differences in memory performance.
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Mood, motivation, and misinformation: Aging and affective state influences on memory
Hess, Thomas M.; Popham, Lauren E.; Emery, Lisa; Elliott, Tonya
2014-01-01
Normative age differences in memory have typically been attributed to declines in basic cognitive and cortical mechanisms. The present study examined the degree to which dominant everyday affect might also be associated with age-related memory errors using the misinformation paradigm. Younger and older adults viewed a positive and a negative event, and then were exposed to misinformation about each event. Older adults exhibited a higher likelihood than young adults of falsely identifying misinformation as having occurred in the events. Consistent with expectations, strength of the misinformation effect was positively associated with dominant mood, and controlling for mood eliminated any age effects. Also, motivation to engage in complex cognitive activity was negatively associated with susceptibility to misinformation, and susceptibility was stronger for negative than for positive events. We argue that motivational processes underlie all of the observed effects, and that such processes are useful in understanding age differences in memory performance. PMID:22059441
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Chong, Jessica X; McMillin, Margaret J; Shively, Kathryn M; Beck, Anita E; Marvin, Colby T; Armenteros, Jose R; Buckingham, Kati J; Nkinsi, Naomi T; Boyle, Evan A; Berry, Margaret N; Bocian, Maureen; Foulds, Nicola; Uzielli, Maria Luisa Giovannucci; Haldeman-Englert, Chad; Hennekam, Raoul C M; Kaplan, Paige; Kline, Antonie D; Mercer, Catherine L; Nowaczyk, Malgorzata J M; Klein Wassink-Ruiter, Jolien S; McPherson, Elizabeth W; Moreno, Regina A; Scheuerle, Angela E; Shashi, Vandana; Stevens, Cathy A; Carey, John C; Monteil, Arnaud; Lory, Philippe; Tabor, Holly K; Smith, Joshua D; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J
2015-03-05
Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with "DA2A with severe neurological abnormalities" and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with "atypical" forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s). Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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Tidal Residual Eddies and their Effect on Water Exchange in Puget Sound
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Zhaoqing; Wang, Taiping
Tidal residual eddies are one of the important hydrodynamic features in tidally dominant estuaries and coastal bays, and they could have significant effects on water exchange in a tidal system. This paper presents a modeling study of tides and tidal residual eddies in Puget Sound, a tidally dominant fjord-like estuary in the Pacific Northwest coast, using a three-dimensional finite-volume coastal ocean model. Mechanisms of vorticity generation and asymmetric distribution patterns around an island/headland were analyzed using the dynamic vorticity transfer approach and numerical experiments. Model results of Puget Sound show that a number of large twin tidal residual eddies existmore » in the Admiralty Inlet because of the presence of major headlands in the inlet. Simulated residual vorticities near the major headlands indicate that the clockwise tidal residual eddy (negative vorticity) is generally stronger than the anticlockwise eddy (positive vorticity) because of the effect of Coriolis force. The effect of tidal residual eddies on water exchange in Puget Sound and its sub-basins were evaluated by simulations of dye transport. It was found that the strong transverse variability of residual currents in the Admiralty Inlet results in a dominant seaward transport along the eastern shore and a dominant landward transport along the western shore of the Inlet. A similar transport pattern in Hood Canal is caused by the presence of tidal residual eddies near the entrance of the canal. Model results show that tidal residual currents in Whidbey Basin are small in comparison to other sub-basins. A large clockwise residual circulation is formed around Vashon Island near entrance of South Sound, which can potentially constrain the water exchange between the Central Basin and South Sound.« less
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Rosado, Consolación; Bueno, Elena; Felipe, Carmen; González-Sarmiento, Rogelio
2014-01-01
Autosomal forms of Alport syndrome represent 20% of all patients (15% recessive and 5% dominant). They are caused by mutations in the COL4A3 and COL4A4 genes, which encode a-3 and a-4 collagen IV chains of the glomerular basement membrane, cochlea and eye. Thin basement membrane nephropathy may affect up to 1% of the population. The pattern of inheritance in the 40% of cases is the same as autosomal dominant Alport syndrome: heterozygous mutations in these genes. The aim of this study is to detect new pathogenic mutations in the COL4A4 gene in the patients previously diagnosed with autosomal Alport syndrome and thin basement membrane nephropathy in our hospital. We conducted a clinical and genetic study in eleven patients belonging to six unrelated families with aforementioned clinical symptoms and a negative study of COL4A3 gene. The molecular study was made by conformation of sensitive gel electrophoresis (CSGE) and direct sequencing of the fragments that show an altered electrophoretic migration pattern. We found two pathogenic mutations, not yet described: IVS3 + 1G > C is a replacement of Guanine to Cytosine in position +1 of intron 3, in the splicing region, which leads to a pathogenic mutation. c.4267C > T; p.P1423S is a missense mutation, also considered pathogenic. We also found seven new polymorphisms. We describe two new pathogenic mutations, responsible for autosomal dominant Alport syndrome. The other families of the study were undiagnosed owing to problems in the method employed and the possibility of mutations in other genes, giving rise to other diseases with similar symptoms.
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Early social environment influences the behaviour of a family-living lizard
2017-01-01
Early social environment can play a significant role in shaping behavioural development. For instance, in many social mammals and birds, isolation rearing results in individuals that are less exploratory, shyer, less social and more aggressive than individuals raised in groups. Moreover, dynamic aspects of social environments, such as the nature of relationships between individuals, can also impact the trajectory of development. We tested if being raised alone or socially affects behavioural development in the family-living tree skink, Egernia striolata. Juveniles were raised in two treatments: alone or in a pair. We assayed exploration, boldness, sociability and aggression repeatedly throughout each juvenile's first year of life, and also assessed social interactions between pairs to determine if juveniles formed dominant–subordinate relationships. We found that male and/or the larger skinks within social pairs were dominant. Developing within this social environment reduced skink growth, and subordinate skinks were more prone to tail loss. Thus, living with a conspecific was costly for E. striolata. The predicted negative effects of isolation failed to materialize. Nevertheless, there were significant differences in behavioural traits depending on the social environment (isolated, dominant or subordinate member of a pair). Isolated skinks were more social than subordinate skinks. Subordinate skinks also became more aggressive over time, whereas isolated and dominant skinks showed invariable aggression. Dominant skinks became bolder over time, whereas isolated and subordinate skinks were relatively stable in their boldness. In summary, our study is evidence that isolation rearing does not consistently affect behaviour across all social taxa. Our study also demonstrates that the social environment plays an important role in behavioural development of a family-living lizard. PMID:28573001
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NASA Astrophysics Data System (ADS)
Tan, Ming K.; Yeo, Leslie Y.
2018-04-01
A two-dimensional hybrid numerical method that allows full coupling of the elastic motion in a piezoelectric solid (modeled using a finite-difference time-domain technique) with the resultant compressional flow in a fluid (simulated using a lattice Boltzmann scheme) is developed to study the acoustic streaming that arises in both microchannels and nanochannels under surface acoustic wave (SAW) excitation. In addition to verifying the model through a comparison of the simulations with results from experimental and numerical studies of microchannel and nanochannel flows driven by both standing and traveling SAWs in the literature, we highlight salient features of the flow field that arise and discuss the underlying mechanisms responsible for the flow. In microchannels, boundary layer streaming is the dominant mechanism when the channel height is below the sound wavelength in the liquid, whereas Eckart streaming—arising as a consequence of the attenuation of the sound wave in the liquid—dominates in the form of periodic vortices for larger channel heights. The absence of Eckart streaming and the overlapping of boundary layers in nanochannels with heights below the boundary layer thickness, on the other hand, give rise to a time-averaged dynamic acoustic pressure that results in an inertial-dominant flow, which paradoxically possesses a parabolic-like velocity profile resembling pressure-driven laminar flow. In contrast, if the nanochannel were to be filled instead with air, the significantly lower fluid density leads to a considerable reduction in the dynamic acoustic pressure and hence inertial forcing such that boundary layer streaming once again dominates, asymptotically imposing a slip condition along the channel surface that results in a negative pluglike velocity profile.
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Cooper, Helen M.; Yang, Yang; Ylikallio, Emil; Khairullin, Rafil; Woldegebriel, Rosa; Lin, Kai-Lan; Euro, Liliya; Palin, Eino; Wolf, Alexander; Trokovic, Ras; Isohanni, Pirjo; Kaakkola, Seppo; Auranen, Mari; Lönnqvist, Tuula; Wanrooij, Sjoerd
2017-01-01
Abstract De novo mutations in ATAD3A (ATPase family AAA-domain containing protein 3A) were recently found to cause a neurological syndrome with developmental delay, hypotonia, spasticity, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. Using whole-exome sequencing, we identified a dominantly inherited heterozygous variant c.1064G > A (p.G355D) in ATAD3A in a mother presenting with hereditary spastic paraplegia (HSP) and axonal neuropathy and her son with dyskinetic cerebral palsy, both with disease onset in childhood. HSP is a clinically and genetically heterogeneous disorder of the upper motor neurons. Symptoms beginning in early childhood may resemble spastic cerebral palsy. The function of ATAD3A, a mitochondrial inner membrane AAA ATPase, is yet undefined. AAA ATPases form hexameric rings, which are catalytically dependent on the co-operation of the subunits. The dominant-negative patient mutation affects the Walker A motif, which is responsible for ATP binding in the AAA module of ATAD3A, and we show that the recombinant mutant ATAD3A protein has a markedly reduced ATPase activity. We further show that overexpression of the mutant ATAD3A fragments the mitochondrial network and induces lysosome mass. Similarly, we observed altered dynamics of the mitochondrial network and increased lysosomes in patient fibroblasts and neurons derived through differentiation of patient-specific induced pluripotent stem cells. These alterations were verified in patient fibroblasts to associate with upregulated basal autophagy through mTOR inactivation, resembling starvation. Mutations in ATAD3A can thus be dominantly inherited and underlie variable neurological phenotypes, including HSP, with intrafamiliar variability. This finding extends the group of mitochondrial inner membrane AAA proteins associated with spasticity. PMID:28158749
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Diurnal patterns of methane flux from a seasonal wetland: mechanisms and methodology
Bansal, Sheel; Tangen, Brian; Finocchiaro, Raymond
2018-01-01
Methane emissions from wetlands are temporally dynamic. Few chamber-based studies have explored diurnal variation in methane flux with high temporal replication. Using an automated sampling system, we measured methane flux every 2.5 to 4 h for 205 diel cycles during three growing seasons (2013–2015) from a seasonal wetland in the Prairie Pothole Region of North America. During ponded conditions, fluxes were generally positive (i.e., methanogenesis dominant, 10.1 ± 0.8 mg m−2 h−1), had extreme range of variation (from −1 to 70 mg m−2 h−1), and were highest during late day. In contrast, during dry conditions fluxes were very low and primarily negative (i.e., oxidation dominant, −0.05 ± 0.002 mg m−2 h−1), with the highest (least negative) fluxes occurring at pre-dawn. During semi-saturated conditions, methane fluxes also were very low, oscillated between positive and negative values (i.e., balanced between methanogenesis and methane oxidation), and exhibited no diel pattern. Methane flux was positively correlated with air temperature during ponded conditions (r = 0.57) and negatively during dry conditions (r = −0.42). Multiple regression analyses showed that temperature, light and water-filled pore space explained 72% of variation in methane flux. Methane fluxes are highly temporally dynamic and follow contrasting diel patterns that are dependent on dominant microbial processes influenced by saturation state.
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NASA Astrophysics Data System (ADS)
Molina, J.; Ibar, Edo; Swinbank, A. M.; Sobral, D.; Best, P. N.; Smail, I.; Escala, A.; Cirasuolo, M.
2017-04-01
We present adaptive optics (AO) assisted SINFONI integral field unit (IFU) spectroscopy of 11 Hα emitting galaxies selected from the High-Z Emission Line Survey (HiZELS). We obtain spatially resolved dynamics on ˜kpc-scales of star-forming galaxies [stellar mass M⋆ = 109.5 - 10.5 M⊙ and star formation rate (SFR) = 2-30 M⊙ yr-1] near the peak of the cosmic star formation rate history. Combining these observations with our previous SINFONI-HiZELS campaign, we construct a sample of 20 homogeneously selected galaxies with IFU AO-aided observations - the 'SHiZELS' survey, with roughly equal number of galaxies per redshift slice, at z = 0.8, 1.47 and 2.23. We measure the dynamics and identify the major kinematic axis by modelling their velocity fields to extract rotational curves and infer their inclination-corrected rotational velocities. We explore the stellar mass Tully-Fisher relationship, finding that galaxies with higher velocity dispersions tend to deviate from this relation. Using kinemetry analyses, we find that galaxy interactions might be the dominant mechanism controlling the star formation activity at z = 2.23 but they become gradually less important down to z = 0.8. Metallicity gradients derived from the [N II]/Hα emission line ratio show a median negative gradient for the SHiZELS survey of Δlog(O/H)/ΔR = -0.026 ± 0.008 dex kpc-1. We find that metal-rich galaxies tend to show negative gradients, whereas metal-poor galaxies tend to exhibit positive metallicity gradients. This result suggests that the accretion of pristine gas in the periphery of galaxies plays an important role in replenishing the gas in 'typical' star-forming galaxies.
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Accumulation of dislocation loops in the α phase of Zr Excel alloy under heavy ion irradiation
NASA Astrophysics Data System (ADS)
Yu, Hongbing; Yao, Zhongwen; Idrees, Yasir; Zhang, He K.; Kirk, Mark A.; Daymond, Mark R.
2017-08-01
In-situ heavy ion irradiations were performed on the high Sn content Zr alloy 'Excel', measuring type dislocation loop accumulation up to irradiation damage doses of 10 dpa at a range of temperatures. The high content of Sn, which diffuses slowly, and the thin foil geometry of the sample provide a unique opportunity to study an extreme case where displacement cascades dominate the loop formation and evolution. The dynamic observation of dislocation loop evolution under irradiation at 200 °C reveals that type dislocation loops can form at very low dose (0.0025 dpa). The size of the dislocation loops increases slightly with irradiation damage dose. The mechanism controlling loop growth in this study is different from that in neutron irradiation; in this study, larger dislocation loops can condense directly from the interaction of displacement cascades and the high concentration of point defects in the matrix. The size of the dislocation loop is dependent on the point defect concentration in the matrix. A negative correlation between the irradiation temperature and the dislocation loop size was observed. A comparison between cascade dominated loop evolution (this study), diffusion dominated loop evolution (electron irradiation) and neutron irradiation suggests that heavy ion irradiation alone may not be enough to accurately reproduce neutron irradiation induced loop structures. An alternative method is proposed in this paper. The effects of Sn on the displacement cascades, defect yield, and the diffusion behavior of point defects are established.
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Student perception of group dynamics predicts individual performance: Comfort and equity matter
Theobald, Elli J.; Eddy, Sarah L.; Grunspan, Daniel Z.; Wiggins, Benjamin L.
2017-01-01
Active learning in college classes and participation in the workforce frequently hinge on small group work. However, group dynamics vary, ranging from equitable collaboration to dysfunctional groups dominated by one individual. To explore how group dynamics impact student learning, we asked students in a large-enrollment university biology class to self-report their experience during in-class group work. Specifically, we asked students whether there was a friend in their group, whether they were comfortable in their group, and whether someone dominated their group. Surveys were administered after students participated in two different types of intentionally constructed group activities: 1) a loosely-structured activity wherein students worked together for an entire class period (termed the ‘single-group’ activity), or 2) a highly-structured ‘jigsaw’ activity wherein students first independently mastered different subtopics, then formed new groups to peer-teach their respective subtopics. We measured content mastery by the change in score on identical pre-/post-tests. We then investigated whether activity type or student demographics predicted the likelihood of reporting working with a dominator, being comfortable in their group, or working with a friend. We found that students who more strongly agreed that they worked with a dominator were 17.8% less likely to answer an additional question correct on the 8-question post-test. Similarly, when students were comfortable in their group, content mastery increased by 27.5%. Working with a friend was the single biggest predictor of student comfort, although working with a friend did not impact performance. Finally, we found that students were 67% less likely to agree that someone dominated their group during the jigsaw activities than during the single group activities. We conclude that group activities that rely on positive interdependence, and include turn-taking and have explicit prompts for students to explain their reasoning, such as our jigsaw, can help reduce the negative impact of inequitable groups. PMID:28727749
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ERIC Educational Resources Information Center
Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John
2010-01-01
Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…
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Klupp, Barbara G; Hellberg, Teresa; Granzow, Harald; Franzke, Kati; Dominguez Gonzalez, Beatriz; Goodchild, Rose E; Mettenleiter, Thomas C
2017-10-01
Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes. The linker of nucleoskeleton and cytoskeleton (LINC) complex consists of INM proteins with a luminal SUN (Sad1/UNC-84 homology) domain connected to ONM proteins with a KASH (Klarsicht, ANC-1, SYNE homology) domain and is thought to be responsible for spacing the nuclear membranes. To investigate the role of the LINC complex during herpesvirus infection, we generated cell lines constitutively expressing dominant negative (dn) forms of SUN1 and SUN2. Ultrastructural analyses revealed a significant expansion of the PNS and the contiguous intracytoplasmic lumen, most likely representing endoplasmic reticulum (ER), especially in cells expressing dn-SUN2. After infection, primary virions accumulated in these expanded luminal regions, also very distant from the nucleus. The importance of the LINC complex was also confirmed by reduced progeny virus titers in cells expressing dn-SUN2. These data show that the intact LINC complex is required for efficient nuclear egress of herpesviruses, likely acting to promote fusion of primary enveloped virions with the ONM. IMPORTANCE While the viral factors for primary envelopment of nucleocapsids at the inner nuclear membrane are known to the point of high-resolution structures, the roles of cellular components and regulators remain enigmatic. Furthermore, the machinery responsible for fusion with the outer nuclear membrane is unsolved. We show here that dominant negative SUN2 interferes with efficient herpesvirus nuclear egress, apparently by interfering with fusion between the primary virion envelope and outer nuclear membrane. This identifies a new cellular component important for viral egress and implicates LINC complex integrity in nonconventional nuclear membrane trafficking. Copyright © 2017 American Society for Microbiology.
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Reddi, Honey V; Madde, Pranathi; Milosevic, Dragana; Hackbarth, Jennifer S; Algeciras-Schimnich, Alicia; McIver, Bryan; Grebe, Stefan K G; Eberhardt, Norman L
2011-01-01
In vitro studies have demonstrated that the PAX8/PPARγ fusion protein (PPFP), which occurs frequently in follicular thyroid carcinomas (FTC), exhibits oncogenic activity. However, paradoxically, a meta-analysis of extant tumor outcome studies indicates that 68% of FTC-expressing PPFP are minimally invasive compared to only 32% of those lacking PPFP (χ(2) = 6.86, P = 0.008), suggesting that PPFP favorably impacts FTC outcomes. In studies designed to distinguish benign thyroid neoplasms from thyroid carcinomas, the previously identified tumor suppressor miR-122, a major liver micro-RNA (miR) that is decreased in hepatocellular carcinoma, was increased 8.9-fold (P < 0.05) in all FTC versus normal, 9.2-fold in FTC versus FA (P < 0.05), and 16.8-fold (P < 0.001) in FTC + PPFP versus FTC - PPFP. Constitutive expression of PPFP in the FTC-derived cell line WRO (WRO-PPFP) caused a 5-fold increase of miR-122 expression (P < 0.05) and a striking 5.1-fold reduction (P < 0.0001) in tumor progression compared to WRO-vector cells in a mouse xenograft model. Constitutive expression of either miR-122 or a dominant-negative PPARγ mutant in WRO cells was less effective than PPFP at inhibiting xenograft tumor progression (1.8-fold [P < 0.001] and 1.7-fold [P < 0.03], respectively). PPFP-induced up-regulation of miR-122 expression was independent of its known dominant-negative PPARγ activity. Up-regulation of miR-122 negatively regulates ADAM-17, a known downstream target, in thyroid cells, suggesting an antiangiogenic mechanism in thyroid carcinoma. This latter inference is directly supported by reduced CD-31 expression in WRO xenografts expressing PPFP, miR-122, and DN-PPARγ. We conclude that, in addition to its apparent oncogenic potential in vitro, PPFP exhibits paradoxical tumor suppressor activity in vivo, mediated by multiple mechanisms including up-regulation of miR-122 and dominant-negative inhibition of PPARγ activity.
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ERIC Educational Resources Information Center
Monahan, Jennifer L.; Laliker, Melanie
2002-01-01
Examines mechanisms that may account for why evaluations made by participants involved in conversations are more influenced by subliminal negative cues than are evaluations made by observers. Explains three studies in which subliminal priming tasks were used with differing cognitive loads and self-preservation concerns among a group of…
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Knight, Erik L; Christian, Colton B; Morales, Pablo J; Harbaugh, William T; Mayr, Ulrich; Mehta, Pranjal H
2017-11-01
Stress often precedes the onset of mental health disorders and is linked to negative impacts on physical health as well. Prior research indicates that testosterone levels are related to reduced stress reactivity in some cases but correlate with increased stress responses in other cases. To resolve these inconsistencies, we tested the causal influence of testosterone on stress reactivity to a social-evaluative stressor. Further, prior work has failed to consider status-relevant individual differences such as trait dominance that may modulate the influence of testosterone on responses to stressors. Participants (n=120 males) were randomly assigned to receive exogenous testosterone or placebo (n=60 testosterone treatment group) via topical gel prior to a well-validated social-evaluative stressor. Compared to placebo, testosterone significantly increased cortisol and negative affect in response to the stressor, especially for men high in trait dominance (95% confidence intervals did not contain zero). The findings suggest that the combination of high testosterone and exposure to status-relevant social stress may confer increased risk for stress-mediated disorders, particularly for individuals high in trait dominance. Copyright © 2017 Elsevier Ltd. All rights reserved.
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An investigation of immune system disorder as a "marker" for anomalous dominance.
Rich, D A; McKeever, W F
1990-01-01
Geschwind and Galaburda (1987) proposed that immune disorder (ID) susceptibility, along with left handedness and familial sinistrality (FS), is a "marker" for anomalous dominance. The theory predicts lesser left lateralization for language processes, lessened left hemisphere abilities, and enhanced right hemisphere abilities. We assessed language laterality (dichotic consonant vowel task) and performances on spatial and verbal tasks. Subjects were 128 college students. The factors of handedness, sex, FS, and immune disorder history (negative or positive) were perfectly counterbalanced. Left-handers were significantly less lateralized for language and scored lower than right-handers on the spatial tasks. Females scored lower on mental rotation than males, but performed comparably to males on the spatial relations task. The only effect of ID was by way of interaction with FS on both spatial tasks--subjects who were either negative or positive on both FS and ID status factors scored significantly higher than subjects negative for one but positive for the other factor. A speculative explanatory model for this interaction was proposed. The model incorporates the notion that FS and ID factors are comparably correlated, but in opposite directions, with hormonal factors implicated by other research as relevant for spatial ability differences. Finally, no support for the "anomalous dominance" hypothesis predictions was found.
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Evolutionary dynamics of sporophytic self-incompatibility alleles in plants.
Schierup, M H; Vekemans, X; Christiansen, F B
1997-10-01
The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model of gametophytic self-incompatibility, but the selection intensity is stronger. With dominance, dominant alleles invade the population more easily than recessive alleles and have a lower frequency at equilibrium. In the SSIdom model, recessive alleles have both a higher allele frequency and higher expected life span. In the SSIdomcod model, however, loss due to drift occurs more easily for pollen-recessive than for pollen-dominant alleles, and therefore, dominant alleles have a higher expected life span than the more recessive alleles. The process of allelic turnover in the SSIdomcod and SSIdom models is closely approximated by a random walk on a dominance ladder. Implications of the results for experimental studies of sporophytic self-incompatibility in natural populations are discussed.
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Majidi, Shideh; Fouts, Alexandra; Pyle, Laura; Chambers, Christina; Armstrong, Taylor; Wang, Zhenyuan; Batish, Sat Dev; Klingensmith, Georgeanna; Steck, Andrea K
2018-02-01
Maturity-onset diabetes of the young (MODY) is an antibody-negative, autosomal dominant form of diabetes. With the increasing prevalence of diabetes and the expense of MODY testing, markers to identify those who need further genetic testing would be beneficial. We investigated whether HLA genotypes, random C-peptide, and/or high-sensitivity C-reactive protein (hsCRP) levels could be helpful biomarkers for identifying MODY in antibody-negative diabetes. Subjects (N = 97) with diabetes onset ≤age 25, measurable C-peptide (≥0.1 ng/mL), and negative for all four diabetes autoantibodies were enrolled at a large academic center and tested for MODY 1-5 through Athena Diagnostics. A total of 22 subjects had a positive or very likely pathogenic mutation for MODY. Random C-peptide levels were significantly different between MODY-positive and MODY-negative subjects (0.16 nmol/L vs. 0.02 nmol/L; P = 0.02). After adjusting for age and diabetes duration, hsCRP levels were significantly lower in MODY-positive subjects (0.37 mg/L vs. 0.87 mg/L; P = 0.02). Random C-peptide level ≥0.15 nmol/L obtained at ≥6 months after diagnosis had 83% sensitivity for diagnosis of MODY with a negative predictive value of 96%. Receiver operating characteristic curves showed that area under the curve for random C-peptide (0.75) was significantly better than hsCRP (0.54), high-risk HLA DR3/4-DQB1*0302 (0.59), and high-risk HLA/random C-peptide combined (0.54; P = 0.03). Random C-peptide obtained at ≥6 months after diagnosis can be a useful biomarker to identify antibody-negative individuals who need further genetic testing for MODY, whereas hsCRP and HLA do not appear to improve this antibody/C-peptide-based approach.
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The Drosophila Insulin Receptor Independently Modulates Lifespan and Locomotor Senescence
Boylan, Michael; Achall, Rajesh; Shirras, Alan; Broughton, Susan J.
2015-01-01
The Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence. To investigate this role in Drosophila melanogaster, we measured the effect of reduced IIS on senescence of two locomotor behaviours, negative geotaxis and exploratory walking. Two long-lived fly models with systemic IIS reductions (daGAL4/UAS-InRDN (ubiquitous expression of a dominant negative insulin receptor) and d2GAL/UAS-rpr (ablation of insulin-like peptide producing cells)) showed an amelioration of negative geotaxis senescence similar to that previously reported for the long-lived IIS mutant chico. In contrast, exploratory walking in daGAL4/UAS-InRDN and d2GAL/UAS-rpr flies declined with age similarly to controls. To determine the contribution of IIS in the nervous system to these altered senescence patterns and lifespan, the InRDN was targeted to neurons (elavGAL4/UAS-InRDN), which resulted in extension of lifespan in females, normal negative geotaxis senescence in males and females, and detrimental effects on age-specific exploratory walking behaviour in males and females. These data indicate that the Drosophila insulin receptor independently modulates lifespan and age-specific function of different types of locomotor behaviour. The data suggest that ameliorated negative geotaxis senescence of long-lived flies with systemic IIS reductions is due to ageing related effects of reduced IIS outside the nervous system. The lifespan extension and coincident detrimental or neutral effects on locomotor function with a neuron specific reduction (elavGAL4/UAS-InRDN) indicates that reduced IIS is not beneficial to the neural circuitry underlying the behaviours despite increasing lifespan. PMID:26020640
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Debeb, Bisrat G; Lacerda, Lara; Xu, Wei; Larson, Richard; Solley, Travis; Atkinson, Rachel; Sulman, Erik P.; Ueno, Naoto T; Krishnamurthy, Savitri; Reuben, James M; Buchholz, Thomas A; Woodward, Wendy A
2015-01-01
Recent studies have shown that differentiated cancer cells can de-differentiate into cancer stem cells (CSCs) although to date no studies have reported whether this transition is influenced by systemic anti-cancer agents. Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that promotes self renewal and expansion of hematopietic stem cells and facilitates the generation of induced pluripotent stem cells from somatic cells and is currently being investigated in breast cancer clinical trials. We hypothesized that HDAC inhibitors reprogram differentiated cancer cells towards the more resistant stem cell-like state. Two highly aggressive breast cancer cell lines, SUM159 and MDA-231, were FACS-sorted based on ALDH activity and subsequently ALDH-negative and ALDH-positive cells were treated with one of two known HDAC inhibitors, VA or SAHA (suberoylanilide hydroxamic acid). In addition, primary tumor cells from patients with metastatic breast cancer were evaluated for ALDH activity following treatment with HDAC inhibitors. We demonstrate that single cell sorted ALDH- negative cells spontaneously generated ALDH-positive cells in vitro. Treatment of ALDH-negative cells with HDAC inhibitors promoted the expansion of ALDH-positive cells and increased mammosphere forming efficiency. Most importantly, it significantly increased the tumor-initiating capacity of ALDH- negative cells in limiting dilution outgrowth assays. Moreover, while HDAC inhibitors upregulated β-catenin expression and significantly increased WNT reporter activity, a TCF4 dominant negative construct abolished HDAC-inhibitor induced expansion of CSCs. These results demonstrate that HDAC inhibitors promote the expansion of breast CSCs through dedifferentiation and have important clinical implications for the use of HDAC inhibitors in the treatment of cancer. PMID:22961641
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Liu, Xiang; Zhao, Ji-Feng; Wang, Chang-Hua; Zhang, Zhi-Wei; Qin, Song-Yun; Zhong, Guo-Yue
2014-07-01
Based on the 2 x 2 contingency table, by using multi-species relevance (variance ratio, VR), chi2-test, Ochiai index, Dice index, Jaccard index, t-test of v/x and F-test of Morisita, s index, the interspecific relationships and the spatial distribution pattern between 20 dominants in Kangding Zheduo Mountain of Sichuan province were studied. The results indicated that the interspecific association between dominants of Sinopodophyllum hexandrum community in this area did not show significant association, which suggested that the S. hexandrum community was in mature stage, and showed stronger independency, among total 190 pairs in 20 dominant species, 2 species pairs exhibited extremely significantly positive association, 12 species pairs showed significantly positive association, 6 species pairs exhibited significantly negative association and there were no pairs showed extremely significantly negative association. S. hexandrum in community did not show significant association, which indicates they are independent in community, the spatial distribution pattern of S. hexandrum is characterized by random distribution.
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Boudjemad, Valérian; Gana, Kamel
2009-12-01
ABSTRACTThis article presents two studies dealing with ageism. The objective of the first study was to adapt to French language and validate the Fraboni of Ageism Scale-Revised (FSA-R) which contains 23 items, while the objective of the second study was to test a structural model containing ageism as measured by the FSA-R and the "Big Three": empathy, social dominance orientation, and dogmatism, controlled for by sex and age. The results of the first study (n = 323) generated a version of the FSA-R comprising 14 items, of which the psychometric properties were very satisfactory. Using structural equation modelling and bootstrap procedure, the results of the second study (n = 284) showed a direct negative and significant effect of empathy on agism. They also showed that this negative effect was mediated by dogmatism and social dominance orientation, which both exerted a positive effect on ageism.
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Abolhasani, Mohammad Mahdi; Naebe, Minoo; Jalali-Arani, Azam; Guo, Qipeng
2014-01-01
In this paper, intercalation of nanoclay in the miscible polymer blend of poly(vinylidene fluoride) (PVDF) and acrylic rubber(ACM) was studied. X-ray diffraction was used to investigate the formation of nanoscale polymer blend/clay hybrid. Infrared spectroscopy and X-ray analysis revealed the coexistence of β and γ crystalline forms in PVDF/Clay nanocomposite while α crystalline form was found to be dominant in PVDF/ACM/Clay miscible hybrids. Flory-Huggins interaction parameter (B) was used to further explain the miscibility phenomenon observed. The B parameter was determined by combining the melting point depression and the binary interaction model. The estimated B values for the ternary PVDF/ACM/Clay and PVDF/ACM pairs were all negative, showing both proper intercalation of the polymer melt into the nanoclay galleries and the good miscibility of PVDF and ACM blend. The B value for the PVDF/ACM blend was almost the same as that measured for the PVDF/ACM/Clay hybrid, suggesting that PVDF chains in nanocomposite hybrids interact with ACM chains and that nanoclay in hybrid systems is wrapped by ACM molecules.
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Najjar, Imen; Schischmanoff, Pierre Olivier; Baran-Marszak, Fanny; Deglesne, Pierre-Antoine; Youlyouz-Marfak, Ibtissam; Pampin, Mathieu; Feuillard, Jean; Bornkamm, Georg W; Chelbi-Alix, Mounira K; Fagard, Remi
2008-12-01
Alternate splicing of STAT1 produces two isoforms: alpha, known as the active form, and beta, previously shown to act as a dominant-negative factor. Most studies have dealt with STAT1alpha, showing its involvement in cell growth control and cell death. To examine the specific function of either isoform in cell death, a naturally STAT1-deficient human B cell line was transfected to express STAT1alpha or STAT1beta. STAT1alpha, expressed alone, enhanced cell death, potentiated the fludarabine-induced apoptosis, and enhanced the nuclear location, the phosphorylation, and the transcriptional activity of p53. Unexpectedly, STAT1beta, expressed alone, induced cell death through a mechanism that was independent of the nuclear function of p53. Indeed, in STAT1beta-expressing B cells, p53 was strictly cytoplasmic where it formed clusters, and there was no induction of the transcriptional activity of p53. These data reveal a novel role of STAT1beta in programmed cell death, which is independent of p53.
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Ramalho, José S; Anders, Ross; Jaissle, Gesine B; Seeliger, Mathias W; Huxley, Clare; Seabra, Miguel C
2002-01-01
Background Transgenic mice have proven to be a powerful system to study normal and pathological gene functions. Here we describe an attempt to generate a transgenic mouse model for choroideremia (CHM), a slow-onset X-linked retinal degeneration caused by mutations in the Rab Escort Protein-1 (REP1) gene. REP1 is part of the Rab geranylgeranylation machinery, a modification that is essential for Rab function in membrane traffic. The loss of REP1 in CHM patients may trigger retinal degeneration through its effects on Rab proteins. We have previously reported that Rab27a is the Rab most affected in CHM lymphoblasts and hypothesised that the selective dysfunction of Rab27a (and possibly a few other Rab GTPases) plays an essential role in the retinal degenerative process. Results To investigate this hypothesis, we generated several lines of dominant-negative, constitutively-active and wild-type Rab27a (and Rab27b) transgenic mice whose expression was driven either by the pigment cell-specific tyrosinase promoter or the ubiquitous β-actin promoter. High levels of mRNA and protein were observed in transgenic lines expressing wild-type or constitutively active Rab27a and Rab27b. However, only modest levels of transgenic protein were expressed. Pulse-chase experiments suggest that the dominant-negative proteins, but not the constitutively-active or wild type proteins, are rapidly degraded. Consistently, no significant phenotype was observed in our transgenic lines. Coat-colour was normal, indicating normal Rab27a activity. Retinal function as determined by fundoscopy, angiography, electroretinography and histology was also normal. Conclusions We suggest that the instability of the dominant-negative mutant Rab27 proteins in vivo precludes the use of this approach to generate mouse models of disease caused by Rab27 GTPases. PMID:12401133
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Gewirtz, Andrew T; Vijay-Kumar, Matam; Brant, Steven R; Duerr, Richard H; Nicolae, Dan L; Cho, Judy H
2006-06-01
Crohn's disease (CD) is associated with elevated adaptive immunity to commensal microbes, with flagellin being a dominant antigen. In light of heightened awareness of the importance of innate immunity in regulating adaptive immunity and ambiguity as to the role of CD-associated immune responses in CD pathophysiology, we sought to determine whether natural acquisition of immune responses to flagellin were regulated by the innate immune flagellin receptor toll-like receptor 5 (TLR5) and determine whether persons carrying a recently defined common dominant-negative TLR5 polymorphism (TLR5-stop) might be protected from developing CD. Carriage rates of a recently defined dominant-negative TLR5 polymorphism (TLR5-stop) and levels of serum immunoreactivity to bacterial products were measured in inflammatory bowel disease patients, first-degree relatives, and unrelated controls. We observed that, in healthy subjects, persons carrying TLR5-stop had significantly lower levels of flagellin-specific IgG and IgA but had similar levels of total and LPS-specific Ig. Moreover, we observed that, among Jewish subjects, the carriage rate of TLR5-stop (in heterozygous state) was significantly less in CD patients, but not ulcerative colitis (UC) patients, compared with unaffected relatives and unrelated controls (5.4, 0.9, 6.0, and 6.5% for unaffected relatives, CD, UC, and unrelated Jewish controls, respectively, n = 296, 215, 185, and 416, respectively; P = 0.037 by likelihood calculation for CD vs. controls), indicating that TLR5-stop can protect persons of Jewish ethnicity against CD. We did not observe a significant association of TLR5-stop with CD in a non-Jewish cohort (11.1, 10.4, and 11.7% for unaffected relatives, CD, and UC, respectively; n = 841, 543, and 300 for unaffected relatives, respectively). These results demonstrate that natural acquisition of immune responses to flagellin are regulated by TLR5 and suggest that immune responses to flagellin are not merely associated with CD but rather promote the pathogenic response.
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Utility functions predict variance and skewness risk preferences in monkeys
Genest, Wilfried; Stauffer, William R.; Schultz, Wolfram
2016-01-01
Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness-risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals’ preferences followed both second-order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals’ preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys’ choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences. PMID:27402743
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Material composition of the basalt-trachyte series of the early Devonian of the Saralin graben-rift
NASA Astrophysics Data System (ADS)
Grinev, O. M.; Grinev, R. O.; Bogorodov, A. A.; Adylbaev, R. R.
2017-12-01
The article clarifies the structural-tectonic position of the Saralin graben. It is determined that, along with the Balyksinsky graben located to the south and the Goryachegorsky volcanic plateau to the north, they are the connecting structural links between the Kuznetsk-Alatau alkaline province and the adjacent Minusinsk trough. In the early Devonian, the alkaline province was formed as a vaulted-block structure (the “shoulder” of the rift), and the Minusinsk deflection as a depression with the dominant volcanism in it. The boundary between these positive and negative structures was the deep Balyksinsko-Saralinsky fault. In the stratigraphic section of the graben, the lower molassoid part (Ustkundustylskaya stratum), the middle trachybasaltoid stratum (Bazarskay) and the upper problematic Ashpanian stratum are distinguished. In addition to analcime basalts, a large extrusive-subvolcanic dome-shaped construction of trachytes is considered. By petrographic and material composition, volcanites of graben are represented by the dominant basalt-trachyte series in the composition of basanites, trachybasalts, trachyandesites, trachytes. The rocks of the basalt-andesibasalt-andesite series are limited. Foidites are rare. Geochemical data indicate the genetic relationship of the volcanics of the studied series. Geochemically, they are clearly specialized in Sc, Ti, Zn, Zr, Th, U, Mn and P. According to the content of some of these elements, the rocks may have an industrial potential. In geodynamic and genetic plans, graben and its volcanics were formed during plume-tectonic processes involving mantle plume, enriched mantle, and recycling processes of these formations with the substance of the consolidated PR-PZ1 cortex.
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Utility functions predict variance and skewness risk preferences in monkeys.
Genest, Wilfried; Stauffer, William R; Schultz, Wolfram
2016-07-26
Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness-risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals' preferences followed both second-order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals' preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys' choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences.
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Chimpanzee Personality and the Arginine Vasopressin Receptor 1A Genotype.
Wilson, V A D; Weiss, A; Humle, T; Morimura, N; Udono, T; Idani, G; Matsuzawa, T; Hirata, S; Inoue-Murayama, M
2017-03-01
Polymorphisms of the arginine vasopressin receptor 1a (AVPR1a) gene have been linked to various measures related to human social behavior, including sibling conflict and agreeableness. In chimpanzees, AVPR1a polymorphisms have been associated with traits important for social interactions, including sociability, joint attention, dominance, conscientiousness, and hierarchical personality dimensions named low alpha/stability, disinhibition, and negative emotionality/low dominance. We examined associations between AVPR1a and six personality domains and hierarchical personality dimensions in 129 chimpanzees (Pan troglodytes) living in Japan or in a sanctuary in Guinea. We fit three linear and three animal models. The first model included genotype, the second included sex and genotype, and the third included genotype, sex, and sex × genotype. All personality phenotypes were heritable. Chimpanzees possessing the long form of the allele were higher in conscientiousness, but only in models that did not include the other predictors; however, additional analyses suggested that this may have been a consequence of study design. In animal models that included sex and sex × genotype, chimpanzees homozygous for the short form of the allele were higher in extraversion. Taken with the findings of previous studies of chimpanzees and humans, the findings related to conscientiousness suggest that AVPR1a may be related to lower levels of impulsive aggression. The direction of the association between AVPR1a genotype and extraversion ran counter to what one would expect if AVPR1a was related to social behaviors. These results help us further understand the genetic basis of personality in chimpanzees.
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A Role for APETALA1/FRUITFULL Transcription Factors in Tomato Leaf Development[C][W
Burko, Yogev; Shleizer-Burko, Sharona; Yanai, Osnat; Shwartz, Ido; Zelnik, Iris Daphne; Jacob-Hirsch, Jasmine; Kela, Itai; Eshed-Williams, Leor; Ori, Naomi
2013-01-01
Flexible maturation rates underlie part of the diversity of leaf shape, and tomato (Solanum lycopersicum) leaves are compound due to prolonged organogenic activity of the leaf margin. The CINCINNATA -TEOSINTE BRANCHED1, CYCLOIDEA, PCF (CIN-TCP) transcription factor LANCEOLATE (LA) restricts this organogenic activity and promotes maturation. Here, we show that tomato APETALA1/FRUITFULL (AP1/FUL) MADS box genes are involved in tomato leaf development and are repressed by LA. AP1/FUL expression is correlated negatively with LA activity and positively with the organogenic activity of the leaf margin. LA binds to the promoters of the AP1/FUL genes MBP20 and TM4. Overexpression of MBP20 suppressed the simple-leaf phenotype resulting from upregulation of LA activity or from downregulation of class I knotted like homeobox (KNOXI) activity. Overexpression of a dominant-negative form of MBP20 led to leaf simplification and partly suppressed the increased leaf complexity of plants with reduced LA activity or increased KNOXI activity. Tomato plants overexpressing miR319, a negative regulator of several CIN-TCP genes including LA, flower with fewer leaves via an SFT-dependent pathway, suggesting that miR319-sensitive CIN-TCPs delay flowering in tomato. These results identify a role for AP1/FUL genes in vegetative development and show that leaf and plant maturation are regulated via partially independent mechanisms. PMID:23771895
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A role for APETALA1/fruitfull transcription factors in tomato leaf development.
Burko, Yogev; Shleizer-Burko, Sharona; Yanai, Osnat; Shwartz, Ido; Zelnik, Iris Daphne; Jacob-Hirsch, Jasmine; Kela, Itai; Eshed-Williams, Leor; Ori, Naomi
2013-06-01
Flexible maturation rates underlie part of the diversity of leaf shape, and tomato (Solanum lycopersicum) leaves are compound due to prolonged organogenic activity of the leaf margin. The CINCINNATA-teosinte branched1, cycloidea, PCF (CIN-TCP) transcription factor lanceolate (LA) restricts this organogenic activity and promotes maturation. Here, we show that tomato APETALA1/fruitfull (AP1/FUL) MADS box genes are involved in tomato leaf development and are repressed by LA. AP1/FUL expression is correlated negatively with LA activity and positively with the organogenic activity of the leaf margin. LA binds to the promoters of the AP1/FUL genes MBP20 and TM4. Overexpression of MBP20 suppressed the simple-leaf phenotype resulting from upregulation of LA activity or from downregulation of class I knotted like homeobox (KNOXI) activity. Overexpression of a dominant-negative form of MBP20 led to leaf simplification and partly suppressed the increased leaf complexity of plants with reduced LA activity or increased KNOXI activity. Tomato plants overexpressing miR319, a negative regulator of several CIN-TCP genes including LA, flower with fewer leaves via an SFT-dependent pathway, suggesting that miR319-sensitive CIN-TCPs delay flowering in tomato. These results identify a role for AP1/FUL genes in vegetative development and show that leaf and plant maturation are regulated via partially independent mechanisms.
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Shin, Sangsu; Song, Yan; Ahn, Jinsoo; Kim, Eunsoo; Chen, Paula; Yang, Shujin; Suh, Yeunsu; Lee, Kichoon
2015-11-15
Myostatin (MSTN) is a key negative regulator of muscle growth and development, and an increase of muscle mass is achieved by inhibiting MSTN signaling. In the current study, five alternative splicing isoforms of MSTN mRNAs in avian species were identified in various tissues. Among these five, three truncated forms of myostatin, MSTN-B, -C, and -E created premature stop codons and produced partial MSTN prodomains encoded from exon 1. MSTN-B is the second dominant isoform following full-length MSTN-A, and their expression was dynamically regulated during muscle development of chicken, turkey, and quail in vivo and in vitro. To clarify the function of MSTN-B, two stable cell lines of quail myoblasts (QM7) were generated to overexpress MSTN-A or MSTN-B. Interestingly, MSTN-B promoted both cell proliferation and differentiation similar to the function of the MSTN prodomain to counteract the negative role of MSTN on myogenesis. The coimmunoprecipitation assay revealed that MSTN-B binds to MSTN-A and reduces the generation of mature MSTN. Furthermore, the current study demonstrated that the partial prodomain encoded from exon 1 is critical for binding of MSTN-B to MSTN-A. Altogether, these data imply that alternative splicing isoforms of MSTN could negatively regulate pro-myostatin processing in muscle cells and prevent MSTN-mediated inhibition of myogenesis in avian species. Copyright © 2015 the American Physiological Society.
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Maestre, Fernando T.; Escolar, Cristina; Bardgett, Richard D.; Dungait, Jennifer A. J.; Gozalo, Beatriz; Ochoa, Victoria
2015-01-01
Soil communities dominated by lichens and mosses (biocrusts) play key roles in maintaining ecosystem structure and functioning in drylands worldwide. However, few studies have explicitly evaluated how climate change-induced impacts on biocrusts affect associated soil microbial communities. We report results from a field experiment conducted in a semiarid Pinus halepensis plantation, where we setup an experiment with two factors: cover of biocrusts (low [<15%] versus high [>50%]), and warming (control versus a ∼2°C temperature increase). Warming reduced the richness and cover (∼45%) of high biocrust cover areas 53 months after the onset of the experiment. This treatment did not change the ratios between the major microbial groups, as measured by phospholipid fatty acid analysis. Warming increased the physiological stress of the Gram negative bacterial community, as indicated by the cy17:0/16:1ω7 ratio. This response was modulated by the initial biocrust cover, as the increase in this ratio with warming was higher in areas with low cover. Our findings suggest that biocrusts can slow down the negative effects of warming on the physiological status of the Gram negative bacterial community. However, as warming will likely reduce the cover and diversity of biocrusts, these positive effects will be reduced under climate change. PMID:26379642
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Reissmann, E; Jörnvall, H; Blokzijl, A; Andersson, O; Chang, C; Minchiotti, G; Persico, M G; Ibáñez, C F; Brivanlou, A H
2001-08-01
Nodal proteins have crucial roles in mesendoderm formation and left-right patterning during vertebrate development. The molecular mechanisms of signal transduction by Nodal and related ligands, however, are not fully understood. In this paper, we present biochemical and functional evidence that the orphan type I serine/threonine kinase receptor ALK7 acts as a receptor for mouse Nodal and Xenopus Nodal-related 1 (Xnr1). Receptor reconstitution experiments indicate that ALK7 collaborates with ActRIIB to confer responsiveness to Xnr1 and Nodal. Both receptors can independently bind Xnr1. In addition, Cripto, an extracellular protein genetically implicated in Nodal signaling, can independently interact with both Xnr1 and ALK7, and its expression greatly enhances the ability of ALK7 and ActRIIB to respond to Nodal ligands. The Activin receptor ALK4 is also able to mediate Nodal signaling but only in the presence of Cripto, with which it can also interact directly. A constitutively activated form of ALK7 mimics the mesendoderm-inducing activity of Xnr1 in Xenopus embryos, whereas a dominant-negative ALK7 specifically blocks the activities of Nodal and Xnr1 but has little effect on other related ligands. In contrast, a dominant-negative ALK4 blocks all mesoderm-inducing ligands tested, including Nodal, Xnr1, Xnr2, Xnr4, and Activin. In agreement with a role in Nodal signaling, ALK7 mRNA is localized to the ectodermal and organizer regions of Xenopus gastrula embryos and is expressed during early stages of mouse embryonic development. Therefore, our results indicate that both ALK4 and ALK7 can mediate signal transduction by Nodal proteins, although ALK7 appears to be a receptor more specifically dedicated to Nodal signaling.
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Reissmann, Eva; Jörnvall, Henrik; Blokzijl, Andries; Andersson, Olov; Chang, Chenbei; Minchiotti, Gabriella; Persico, M. Graziella; Ibáñez, Carlos F.; Brivanlou, Ali H.
2001-01-01
Nodal proteins have crucial roles in mesendoderm formation and left–right patterning during vertebrate development. The molecular mechanisms of signal transduction by Nodal and related ligands, however, are not fully understood. In this paper, we present biochemical and functional evidence that the orphan type I serine/threonine kinase receptor ALK7 acts as a receptor for mouse Nodal and Xenopus Nodal-related 1 (Xnr1). Receptor reconstitution experiments indicate that ALK7 collaborates with ActRIIB to confer responsiveness to Xnr1 and Nodal. Both receptors can independently bind Xnr1. In addition, Cripto, an extracellular protein genetically implicated in Nodal signaling, can independently interact with both Xnr1 and ALK7, and its expression greatly enhances the ability of ALK7 and ActRIIB to respond to Nodal ligands. The Activin receptor ALK4 is also able to mediate Nodal signaling but only in the presence of Cripto, with which it can also interact directly. A constitutively activated form of ALK7 mimics the mesendoderm-inducing activity of Xnr1 in Xenopus embryos, whereas a dominant-negative ALK7 specifically blocks the activities of Nodal and Xnr1 but has little effect on other related ligands. In contrast, a dominant-negative ALK4 blocks all mesoderm-inducing ligands tested, including Nodal, Xnr1, Xnr2, Xnr4, and Activin. In agreement with a role in Nodal signaling, ALK7 mRNA is localized to the ectodermal and organizer regions of Xenopus gastrula embryos and is expressed during early stages of mouse embryonic development. Therefore, our results indicate that both ALK4 and ALK7 can mediate signal transduction by Nodal proteins, although ALK7 appears to be a receptor more specifically dedicated to Nodal signaling. PMID:11485994
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Shin, Jinwook; Park, Boyoun; Lee, Sungwook; Kim, Youngkyun; Biegalke, Bonita J.; Kang, Seongman; Ahn, Kwangseog
2006-01-01
Human cytomegalovirus encodes four unique short (US) region proteins, each of which is independently sufficient for causing the down-regulation of major histocompatibility complex (MHC) class I molecules on the cell surface. This down-regulation enables infected cells to evade recognition by cytotoxic T lymphocytes (CTLs) but makes them vulnerable to lysis by natural killer (NK) cells, which lyse those cells that lack MHC class I molecules. The 22-kDa US3 glycoprotein is able to down-regulate the surface expression of MHC class I molecules by dual mechanisms: direct endoplasmic reticulum retention by physical association and/or tapasin inhibition. The alternative splicing of the US3 gene generates two additional products, including 17-kDa and 3.5-kDa truncated isoforms; however, the functional significance of these isoforms during viral infection is unknown. Here, we describe a novel mode of self-regulation of US3 function that uses the endogenously produced truncated isoform. The truncated isoform itself neither binds to MHC class I molecules nor prevents the full-length US3 from interacting with MHC class I molecules. Instead, the truncated isoform associates with tapasin and competes with full-length US3 for binding to tapasin; thus, it suppresses the action of US3 that causes the disruption of the function of tapasin. Our results indicate that the truncated isoform of the US3 locus acts as a dominant negative regulator of full-length US3 activity. These data reflect the manner in which the virus has developed temporal survival strategies during viral infection against immune surveillance involving both CTLs and NK cells. PMID:16699020
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Lin, Sue-Jane; Chang, Chungming; Ng, Ah-Kau; Wang, Shu-Han; Li, Jia-Je; Hu, Cheng-po
2007-09-01
In this study, we demonstrate that interleukin-4 (IL-4) protects human hepatocellular carcinoma (HCC) cell line Hep3B from apoptosis induced by transforming growth factor-beta (TGF-beta). Further investigation of IL-4-transduced signaling pathways revealed that both insulin response substrate 1 and 2 (IRS-1/-2) and extracellular signal-regulated kinase (ERK) pathways were activated after IL-4 stimulation. The IRS-1/-2 activation was accompanied by the activation of phosphotidylinositol-3-kinase (PI3K), leading to Akt and p70 ribosomal protein S6 kinase (p70S6K). Interestingly, a protein kinase C (PKC) inhibitor, Gö6976, inhibited the phosphorylation of Akt, suggesting that the Akt activation was PKC-dependent. Using specific inhibitors for PI3K or ERK, we demonstrated that the PI3K pathway, but not the ERK pathway, was required for protection. The constitutively active form of PI3K almost completely rescued TGF-beta-induced apoptosis, further supporting the importance of the PI3K pathway in the protective effect of IL-4. Furthermore, a dominant negative Akt and/or Gö6976 only partially blocked the anti-apoptotic effect of IL-4. Similarly, rapamycin, which interrupted the activation of p70S6K, also only partially blocked the protective effect of IL-4. However, in the presence of both rapamycin and dominant negative Akt with or without Gö6976, IL-4 almost completely lost the anti-apoptotic effect, suggesting that both Akt and p70S6K pathways were required for the protective effect of IL-4 against TGF-beta-induced apoptosis.
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MT1-MMP is a crucial promotor of synovial invasion in human rheumatoid arthritis
Miller, Mary-Clare; Manning, Hugh B.; Jain, Abhilash; Troeberg, Linda; Dudhia, Jayesh; Essex, David; Sandison, Ann; Seiki, Motoharu; Nanchahal, Jagdeep; Nagase, Hideaki; Itoh, Yoshifumi
2010-01-01
Objective A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage and this step requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane-type 1 MMP (MT1-MMP), in synovial pannus invasiveness. Methods Expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemistry of RA joints specimens. The functional role of MT1-MMP was analyzed by 3D collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, or GM6001. The effect of adenoviral expression of a dominant negative MT1-MMP construct lacking a catalytic domain was also examined. Results MT1-MMP was highly expressed at the pannus-cartilage junction of RA joints. Freshly isolated rheumatoid synovial tissues and isolated RA synovial fibroblasts invaded into a 3D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001, but not by TIMP-1. It was also inhibited by the over-expression of a dominant negative MT1-MMP which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. Conclusion MT1-MMP is an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may form a novel therapeutic strategy for RA. PMID:19248098
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Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy
Zhang, Wei; Zhang, Xiaoming; Wang, Hui; Sharma, Anil K.; Edwards, Albert O.
2013-01-01
KCNJ13 encodes Kir7.1, an inwardly rectifying K+ channel that is expressed in multiple ion-transporting epithelia. A mutation in KCNJ13 resulting in an arginine-to-tryptophan change at residue 162 (R162W) of Kir7.1 was associated with snowflake vitreoretinal degeneration, an inherited autosomal-dominant disease characterized by vitreous degeneration and mild retinal degeneration. We used the Xenopus laevis oocyte expression system to assess the functional properties of the R162W (mutant) Kir7.1 channel and determine how wild-type (WT) Kir7.1 is affected by the presence of the mutant subunit. Recordings obtained via the two-electrode voltage-clamp technique revealed that injection of oocytes with mutant Kir7.1 cRNA resulted in currents and cation selectivity that were indistinguishable from those in water-injected oocytes, suggesting that the mutant protein does not form functional channels in the plasma membrane. Coinjection of oocytes with equal amounts of mutant and WT Kir7.1 cRNAs resulted in inward K+ and Rb+ currents with amplitudes that were ∼17% of those in oocytes injected with WT Kir7.1 cRNA alone, demonstrating a dominant-negative effect of the mutant subunit. Similar to oocytes injected with WT Kir7.1 cRNA alone, coinjected oocytes exhibited inwardly rectifying Rb+ currents that were more than seven times larger than K+ currents, indicating that mutant subunits did not alter Kir7.1 channel selectivity. Immunostaining of Xenopus oocytes or Madin-Darby canine kidney cells expressing mutant or WT Kir7.1 demonstrated distribution of both proteins primarily in the plasma membrane. Our data suggest that the R162W mutation suppresses Kir7.1 channel activity, possibly by negatively impacting gating by membrane phosphadidylinositol 4,5-bisphosphate. PMID:23255580
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Hannemann, Anke; Christie, Jenny K; Flatman, Peter W
2009-12-18
The renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is the major salt transport pathway in the apical membrane of the mammalian thick ascending limb. It is differentially spliced and the three major variants (A, B, and F) differ in their localization and transport characteristics. Most knowledge about its regulation comes from experiments in Xenopus oocytes as NKCC2 proved difficult to functionally express in a mammalian system. Here we report the cloning and functional expression of untagged and unmodified versions of the major splice variants from ferret kidney (fNKCC2A, -B, and -F) in human embryonic kidney (HEK) 293 cells. Many NKCC2 antibodies used in this study detected high molecular weight forms of the transfected proteins, probably NKCC2 dimers, but not the monomers. Interestingly, monomers were strongly detected by phosphospecific antibodies directed against phosphopeptides in the regulatory N terminus. Bumetanide-sensitive (86)Rb uptake was significantly higher in transfected HEK-293 cells and could be stimulated by incubating cells in a medium containing a low chloride concentration prior the uptake measurements. fNKCC2 was less sensitive to the reduction in chloride concentration than NKCC1. Using HEK-293 cells stably expressing fNKCC2A we also show that co-expression of variant NKCC2AF does not have the dominant-negative effect on NKCC2A activity that was seen in Xenopus oocytes, nor is it trafficked to the cell surface. In addition, fNKCC2AF is neither complex glycosylated nor phosphorylated in its N terminus regulatory region like other variants.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Sun Kyung; Barron, Lindsey; Hinck, Cynthia S.
The transforming growth factor β isoforms, TGF-β1, -β2, and -β3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor (TβRI) but dispensable for binding the other receptor requiredmore » for TGF-β signaling, the TGF-β type II receptor (TβRII), as an alternative therapeutic modality for blocking TGF-β signaling in humans. As shown through binding studies and crystallography, the engineered monomer retained the same overall structure of native TGF-β monomers and bound TβRII in an identical manner. Cell-based luciferase assays showed that the engineered monomer functioned as a dominant negative to inhibit TGF-β signaling with a Ki of 20–70 nM. Investigation of the mechanism showed that the high affinity of the engineered monomer for TβRII, coupled with its reduced ability to non-covalently dimerize and its inability to bind and recruit TβRI, enabled it to bind endogenous TβRII but prevented it from binding and recruiting TβRI to form a signaling complex. Such engineered monomers provide a new avenue to probe and manipulate TGF-β signaling and may inform similar modifications of other TGF-β family members.« less
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Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.
2015-01-01
The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012
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Shin, Jinwook; Park, Boyoun; Lee, Sungwook; Kim, Youngkyun; Biegalke, Bonita J; Kang, Seongman; Ahn, Kwangseog
2006-06-01
Human cytomegalovirus encodes four unique short (US) region proteins, each of which is independently sufficient for causing the down-regulation of major histocompatibility complex (MHC) class I molecules on the cell surface. This down-regulation enables infected cells to evade recognition by cytotoxic T lymphocytes (CTLs) but makes them vulnerable to lysis by natural killer (NK) cells, which lyse those cells that lack MHC class I molecules. The 22-kDa US3 glycoprotein is able to down-regulate the surface expression of MHC class I molecules by dual mechanisms: direct endoplasmic reticulum retention by physical association and/or tapasin inhibition. The alternative splicing of the US3 gene generates two additional products, including 17-kDa and 3.5-kDa truncated isoforms; however, the functional significance of these isoforms during viral infection is unknown. Here, we describe a novel mode of self-regulation of US3 function that uses the endogenously produced truncated isoform. The truncated isoform itself neither binds to MHC class I molecules nor prevents the full-length US3 from interacting with MHC class I molecules. Instead, the truncated isoform associates with tapasin and competes with full-length US3 for binding to tapasin; thus, it suppresses the action of US3 that causes the disruption of the function of tapasin. Our results indicate that the truncated isoform of the US3 locus acts as a dominant negative regulator of full-length US3 activity. These data reflect the manner in which the virus has developed temporal survival strategies during viral infection against immune surveillance involving both CTLs and NK cells.
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Large woody debris and land management in California's hardwood-dominated watersheds.
Opperman, Jeff J
2005-03-01
Although large woody debris (LWD) has been studied extensively in conifer-dominated watersheds, relatively little is known about LWD in hardwood-dominated watersheds. Field surveys of 32 hardwood-dominated stream reaches in northern coastal California revealed that levels of LWD varied with land ownership and that living trees strongly influenced debris jam formation. Almost half of the channel-spanning debris jams, which stored the most wood and were most likely to form a pool, were formed behind a key piece that was still living. These living key pieces might provide greater longevity and stability than would otherwise be expected from hardwood LWD. Compared to streams on private land, streams on public land had significantly greater LWD loading and debris-jam frequency. Land management practices that remove wood from streams might be contributing to the degradation of salmonid habitat in California's hardwood-dominated watersheds.
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ERIC Educational Resources Information Center
Martin, John Levi
2009-01-01
Social psychological investigations of hierarchy formation have been almost entirely confined to the case of task-oriented groups and hence have produced theories that turn on the existence of such a task. But other forms of vertical hierarchy may emerge in non-task groups. One form, orderings of dominance, has been studied among animals using…
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Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.
Minetti, C; Sotgia, F; Bruno, C; Scartezzini, P; Broda, P; Bado, M; Masetti, E; Mazzocco, M; Egeo, A; Donati, M A; Volonte, D; Galbiati, F; Cordone, G; Bricarelli, F D; Lisanti, M P; Zara, F
1998-04-01
Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogeneous group of myopathies, including autosomal dominant and recessive forms. To date, two autosomal dominant forms have been recognized: LGMD1A, linked to chromosome 5q, and LGMD1B, associated with cardiac defects and linked to chromosome 1q11-21. Here we describe eight patients from two different families with a new form of autosomal dominant LGMD, which we propose to call LGMD1C, associated with a severe deficiency of caveolin-3 in muscle fibres. Caveolin-3 (or M-caveolin) is the muscle-specific form of the caveolin protein family, which also includes caveolin-1 and -2. Caveolins are the principal protein components of caveolae (50-100 nm invaginations found in most cell types) which represent appendages or sub-compartments of plasma membranes. We localized the human caveolin-3 gene (CAV3) to chromosome 3p25 and identified two mutations in the gene: a missense mutation in the membrane-spanning region and a micro-deletion in the scaffolding domain. These mutations may interfere with caveolin-3 oligomerization and disrupt caveolae formation at the muscle cell plasma membrane.
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Mechanisms of protein-folding diseases at a glance.
Valastyan, Julie S; Lindquist, Susan
2014-01-01
For a protein to function appropriately, it must first achieve its proper conformation and location within the crowded environment inside the cell. Multiple chaperone systems are required to fold proteins correctly. In addition, degradation pathways participate by destroying improperly folded proteins. The intricacy of this multisystem process provides many opportunities for error. Furthermore, mutations cause misfolded, nonfunctional forms of proteins to accumulate. As a result, many pathological conditions are fundamentally rooted in the protein-folding problem that all cells must solve to maintain their function and integrity. Here, to illustrate the breadth of this phenomenon, we describe five examples of protein-misfolding events that can lead to disease: improper degradation, mislocalization, dominant-negative mutations, structural alterations that establish novel toxic functions, and amyloid accumulation. In each case, we will highlight current therapeutic options for battling such diseases.
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Complexation between sodium dodecyl sulfate and amphoteric polyurethane nanoparticles.
Qiao, Yong; Zhang, Shifeng; Lin, Ouya; Deng, Liandong; Dong, Anjie
2007-09-27
The complexation between negatively charged sodium dodecyl sulfate (SDS) and positively charged amphoteric polyurethane (APU) self-assembled nanoparticles (NPs) containing nonionic hydrophobic segments is studied by dynamic light scattering, pyrene fluorescent probing, zeta-potential, and transmission electron microscopy (TEM) in the present paper. With increasing the mol ratio of SDS to the positive charges on the surface of APU NPs, the aqueous solution of APU NPs presents precipitation at pH 2, around stoichiometric SDS concentration, and then the precipitate dissociates with excess SDS to form more stable nanoparticles of ionomer complexes. Three stages of the complexation process are clearly shown by the pyrene I1/I3 variation of the complex systems, which only depends on the ratio of SDS/APU, and demonstrate that the process is dominated by electrostatic attraction and hydrophobic aggregation.
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Fascaplysin sensitizes cells to TRAIL-induced apoptosis through upregulating DR5 expression
NASA Astrophysics Data System (ADS)
Wang, Feng; Chen, Haimin; Yan, Xiaojun; Zheng, Yanling
2013-05-01
This study investigated the molecular mechanism of anti-tumor effect of fascaplysin, a nitrogenous red pigment firstly isolated from a marine sponge. Microarray analysis show that the TNF and TNF receptor superfamily in human umbilical vein endothelial cells (HUVEC) and human hepatocarcinoma cells (BEL-7402) were significantly regulated by fascaplysin. Western Blot results reveal that fascaplysin increased the expression of cleaved caspase-9, active caspase-3, and decreased the level of procaspase-8 and Bid. Flow cytometry and cytotoxicity tests indicate that fascaplysin sensitized cells to tumor necrosis-related apoptosisinducing ligand-(TRAIL) induced apoptosis, which was markedly blocked by TRAIL R2/Fc chimera, a dominant negative form of TRAIL receptor DR5. Therefore, our results demonstrate that fascaplysin promotes apoptosis through the activation of TRAIL signaling pathway by upregulating DR5 expression.
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SERS spectrum of gallic acid obtained from a modified silver colloid
NASA Astrophysics Data System (ADS)
Garrido, C.; Diaz-Fleming, G.; Campos-Vallette, M. M.
2016-06-01
Two different crystals of the gallic acid were microscopically separated from a p.a. commercial product. The Raman spectra analysis allowed distinguishing monomeric and dimeric structures. The vibrational wave numbers were computed using DFT quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in the Raman spectrum. The dimer, characterized as ellagic acid, involves the carboxyl and hydroxyl moieties. The Raman spectrum in water solution of each species is dominated by the monomeric form. A low negatively charged Ag colloid allowed obtain to the best of our knowledge, the first surface enhanced Raman scattering (SERS) spectrum of the gallic acid. The possible electrophilic attacking sites of the title molecule are identified using MEP surface plot study and the orientation of the analyte on the metal surface is proposed tilted to the surface.
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Proposal for GPD studies at COMPASS
NASA Astrophysics Data System (ADS)
Burtin, E.
2011-10-01
The study of nucleon structure through Generalised Parton Distributions (GPD) is one major part of the future COMPASS-II physics program [1] and can be performed using exclusive reactions like Deeply Virtual Compton Scattering (DVCS) and Meson Production. The high energy of the muon beam allows to measure the xB-dependence of the t-slope of the DVCS cross section. The use of positive and negative polarised muon beams allows to determine the Beam Charge and Spin Difference of the DVCS cross sections to access the real part of the Compton form factor related to the dominant GPD H. The sensitivity of both measurements is examined and confronted to existing models or global fits of the data. Preliminary beam test data were analyzed and demonstrated the feasibility of the identification of the DVCS reaction using the COMPASS experimental set-up.
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Prospects for DVCS measurements using the COMPASS spectrometer at CERN
NASA Astrophysics Data System (ADS)
Kouznetsov, O.
2011-07-01
The study of exclusive reactions like Deeply Virtual Compton Scattering (DVCS) and Deeply Virtual Meson Production (DVMP) is one major part of the future COMPASS program to investigate nucleon structure through Generalized Parton Distributions (GPD). The high energy of the muon beam allows to measure the xBj-dependence of the t-slope of the DVCS cross section and to study nucleon tomography. The use of positive and negative polarized muon beams allows to determine the Beam Charge and Spin Difference of the DVCS cross sections to access the real part of the Compton form factor related to the dominant GPD H. As a second phase a transversely polarized proton target will be used to collect data to constrain the GPD E. In preparation of the future measurements two DVCS test runs were performed in 2008 and 2009.
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A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells.
Ito, Akihiko; Morita, Nobuyoshi; Miura, Daisaku; Koma, Yu-Ichiro; Kataoka, Tatsuki R; Yamasaki, Hiroshi; Kitamura, Yukihiko; Kita, Yasuyuki; Nojima, Hiroshi
2004-10-01
We reported previously that the abnormally augmented expression of connexin 26 (Cx26) is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells, and that the exogenous expression of a dominant negative form of Cx26 inhibits the spontaneous metastasis of BL6. Here we show that daily intraperitoneal (i.p.) injections of oleamide, a sleep-inducing lipid hormone, weakly inhibited the spontaneous metastasis of BL6 cells. To obtain a more effective reagent, 19 oleamide derivatives were chemically synthesized and tested for their ability to inhibit the gap junction-mediated intercellular communications (GJIC) that are formed between HeLa cells by the ectopic expression of Cx26 or Cx43. One of these, denoted metastasis inhibitor-18 (MI-18), inhibited the GJIC formed by Cx26 as well as oleamide but unlike oleamide, which is a non-selective inhibitor of connexin, it did not inhibit the GJIC formed by Cx43. Daily i.p. injections of MI-18 potently blocked the spontaneous metastasis of BL6 cells down to 15% of that in the untreated control mice. MI-18 was safe because even after >7 weeks of daily injections, the survival rate of the mice was 93%. We propose that MI-18 may serve as a novel and clinically important prototype of a potent inhibitor of spontaneous metastasis.
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Hauri, Claudine; Fabricius, Katharina E; Schaffelke, Britta; Humphrey, Craig
2010-09-13
Disturbed coral reefs are often dominated by dense mat- or canopy-forming assemblages of macroalgae. This study investigated how such dense macroalgal assemblages change the chemical and physical microenvironment for understorey corals, and how the altered environmental conditions affect the physiological performance of corals. Field measurements were conducted on macroalgal-dominated inshore reefs in the Great Barrier Reef in quadrats with macroalgal biomass ranging from 235 to 1029 g DW m(-2) dry weight. Underneath mat-forming assemblages, the mean concentration of dissolved oxygen was reduced by 26% and irradiance by 96% compared with conditions above the mat, while concentrations of dissolved organic carbon and soluble reactive phosphorous increased by 26% and 267%, respectively. The difference was significant but less pronounced under canopy-forming assemblages. Dissolved oxygen declined and dissolved inorganic carbon and alkalinity increased with increasing algal biomass underneath mat-forming but not under canopy-forming assemblages. The responses of corals to conditions similar to those found underneath algal assemblages were investigated in an aquarium experiment. Coral nubbins of the species Acropora millepora showed reduced photosynthetic yields and increased RNA/DNA ratios when exposed to conditions simulating those underneath assemblages (pre-incubating seawater with macroalgae, and shading). The magnitude of these stress responses increased with increasing proportion of pre-incubated algal water. Our study shows that mat-forming and, to a lesser extent, canopy-forming macroalgal assemblages alter the physical and chemical microenvironment sufficiently to directly and detrimentally affect the metabolism of corals, potentially impeding reef recovery from algal to coral-dominated states after disturbance. Macroalgal dominance on coral reefs therefore simultaneously represents a consequence and cause of coral reef degradation.
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Hauri, Claudine; Fabricius, Katharina E.; Schaffelke, Britta; Humphrey, Craig
2010-01-01
Disturbed coral reefs are often dominated by dense mat- or canopy-forming assemblages of macroalgae. This study investigated how such dense macroalgal assemblages change the chemical and physical microenvironment for understorey corals, and how the altered environmental conditions affect the physiological performance of corals. Field measurements were conducted on macroalgal-dominated inshore reefs in the Great Barrier Reef in quadrats with macroalgal biomass ranging from 235 to 1029 g DW m−2 dry weight. Underneath mat-forming assemblages, the mean concentration of dissolved oxygen was reduced by 26% and irradiance by 96% compared with conditions above the mat, while concentrations of dissolved organic carbon and soluble reactive phosphorous increased by 26% and 267%, respectively. The difference was significant but less pronounced under canopy-forming assemblages. Dissolved oxygen declined and dissolved inorganic carbon and alkalinity increased with increasing algal biomass underneath mat-forming but not under canopy-forming assemblages. The responses of corals to conditions similar to those found underneath algal assemblages were investigated in an aquarium experiment. Coral nubbins of the species Acropora millepora showed reduced photosynthetic yields and increased RNA/DNA ratios when exposed to conditions simulating those underneath assemblages (pre-incubating seawater with macroalgae, and shading). The magnitude of these stress responses increased with increasing proportion of pre-incubated algal water. Our study shows that mat-forming and, to a lesser extent, canopy-forming macroalgal assemblages alter the physical and chemical microenvironment sufficiently to directly and detrimentally affect the metabolism of corals, potentially impeding reef recovery from algal to coral-dominated states after disturbance. Macroalgal dominance on coral reefs therefore simultaneously represents a consequence and cause of coral reef degradation. PMID:20856882
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ERIC Educational Resources Information Center
Bougie, Evelyne; Wright, Stephen C.; Taylor, Donald M.
2003-01-01
This research explored the impact of the abrupt shift from heritage-language to dominant-language education on Inuit children's personal and collective self-esteem. Specifically, the following question was addressed: will early heritage-language education serve as an inoculation against the potential negative impact of being submerged in a…
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Chun, Minkyu; Um, Jae Gwang; Park, Min Sang
We report the abnormal behavior of the threshold voltage (V{sub TH}) shift under positive bias Temperature stress (PBTS) and negative bias temperature stress (NBTS) at top/bottom gate in dual gate amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistors (TFTs). It is found that the PBTS at top gate shows negative transfer shift and NBTS shows positive transfer shift for both top and bottom gate sweep. The shift of bottom/top gate sweep is dominated by top gate bias (V{sub TG}), while bottom gate bias (V{sub BG}) is less effect than V{sub TG}. The X-ray photoelectron spectroscopy (XPS) depth profile provides the evidence of Inmore » metal diffusion to the top SiO{sub 2}/a-IGZO and also the existence of large amount of In{sup +} under positive top gate bias around top interfaces, thus negative transfer shift is observed. On the other hand, the formation of OH{sup −} at top interfaces under the stress of negative top gate bias shows negative transfer shift. The domination of V{sub TG} both on bottom/top gate sweep after PBTS/NBTS is obviously occurred due to thin active layer.« less
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The zinc finger gene Xblimp1 controls anterior endomesodermal cell fate in Spemann's organizer.
de Souza, F S; Gawantka, V; Gómez, A P; Delius, H; Ang, S L; Niehrs, C
1999-01-01
The anterior endomesoderm of the early Xenopus gastrula is a part of Spemann's organizer and is important for head induction. Here we describe Xblimp1, which encodes a zinc finger transcriptional repressor expressed in the anterior endomesoderm. Xblimp1 represses trunk mesoderm and induces anterior endomesoderm in a cooperative manner with the pan-endodermal gene Mix.1. Furthermore, Xblimp1 can cooperate with the BMP inhibitor chordin to induce ectopic heads, while a dominant-negative Xblimp1 inhibits head formation. The head inducer cerberus is positively regulated by Xblimp1 and is able to rescue microcephalic embryos caused by dominant-negative Xblimp1. Our results indicate that Xblimp1 is required for anterior endomesodermal cell fate and head induction. PMID:10545117
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Compassionate love buffers stress-reactive mothers from fight-or-flight parenting.
Miller, Jonas G; Kahle, Sarah; Lopez, Monica; Hastings, Paul D
2015-01-01
The links among mothers' compassionate love for their child, autonomic nervous system activity, and parenting behavior during less and more challenging mother-child interactions were examined. Mothers expressed and reported less negative affect when they exhibited autonomic patterns of increased parasympathetic dominance (high parasympathetic and low sympathetic activation) or autonomic coactivation (high parasympathetic and high sympathetic activation) during the less challenging interaction and autonomic coactivation during the more challenging interaction. Compassionate love predicted less reported and observed negativity in mothers who showed increased sympathetic nervous system dominance (high sympathetic and low parasympathetic activation). Compassionate love appeared to help mothers, and particularly those who experienced strong physiological arousal during difficult parenting situations, establish positive socialization contexts for their children and avoid stress-induced adverse parenting.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nagahama, Masami; Yamazoe, Takeshi; Hara, Yoshimitsu
2006-08-04
Nuclear VCP/p97-like protein 2 (NVL2) is a member of the chaperone-like AAA-ATPase family with two conserved ATP-binding modules. Our previous studies have shown that NVL2 is localized to the nucleolus by interacting with ribosomal protein L5 and may participate in ribosome synthesis, a process involving various non-ribosomal factors including chaperones and RNA helicases. Here, we show that NVL2 is associated with pre-ribosomal particles in the nucleus. Moreover, we used yeast two-hybrid and co-immunoprecipitation assays to identify an NVL2-interacting protein that could yield insights into NVL2 function in ribosome biogenesis. We found that NVL2 interacts with DOB1, a DExD/H-box RNA helicase,more » whose yeast homologue functions in a late stage of the 60S subunit synthesis. DOB1 can interact with a second ATP-binding module mutant of NVL2, which shows a dominant negative effect on ribosome synthesis. In contrast, it cannot interact with a first ATP-binding module mutant, which does not show the dominant negative effect. When the dominant negative mutant of NVL2 was overexpressed in cells, DOB1 appeared to remain associated with nuclear pre-ribosomal particles. Such accumulation was not observed upon overexpression of wild-type NVL2 or a nondominant-negative mutant. Taken together, our results suggest that NVL2 might regulate the association/dissociation reaction of DOB1 with pre-ribosomal particles by acting as a molecular chaperone.« less
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Blowing bubbles in Lennard-Jonesium along the saturation curve.
Ashbaugh, Henry S
2009-05-28
Extensive molecular simulations of the Lennard-Jones fluid have been performed to determine its liquid-vapor coexistence properties and solvent contact densities with cavities up to ten times the diameter of the solvent from the triple point to the critical point. These simulations are analyzed using a revised scaled-particle theory [H. S. Ashbaugh and L. R. Pratt, Rev. Mod. Phys. 78, 159 (2006)] to evaluate the thermodynamics of cavity solvation and curvature dependent interfacial properties along the saturation curve. While the thermodynamic signatures of cavity solvation are distinct from those in water, exhibiting a chemical potential dominated by a large temperature independent enthalpy, the solvent dewets cavities of increasing size similar with water near coexistence. The interfacial tension for forming a liquid-wall interface is found to be consistently greater than the liquid-vapor surface tension of the Lennard-Jones fluid by up to 10% and potentially reflects the suppression of high amplitude fluctuations at the cavity surface. The first-order curvature correction for the surface tension is negative and appears to diverge to negative infinity at temperatures approaching the critical point. Our results point to the success of the revised scaled-particle theory at bridging molecular and macroscopic descriptions of cavity solvation.
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NASA Astrophysics Data System (ADS)
Seyfferth, A.; Limmer, M. A.; Amaral, D.; Teasley, W.
2017-12-01
Flooded rice agroecosystems favor geochemical conditions that mobilize soil-bound arsenic (As) and produce methane (CH4). These negative outcomes of flooded rice may lead to As exposure upon As-laden rice grain consumption and enhanced greenhouse gas emissions. Periodic draining of fields (e.g., alternate wetting and drying) is effective at minimizing these negative outcomes, but may reduce rice yield, increase toxic Cd in grain, and increase nitrous oxide (N2O) emissions. Because 3 of the 4 dominant chemical form of As in flooded paddy soil share the efficient Si uptake pathway, increasing plant-available Si can decrease toxic As in grain and boost yield, particularly when plants are stressed with As. We used combined pot and field studies to examine the biogeochemical cycling of As, Fe, Si, and C when plants are grown with water and/or Si management, the latter of which under both low and high As conditions. We show that increasing plant-available Si can be used alone or in conjunction with water management to improve rice yields depending on the edaphic conditions. These processes and findings will be discussed in the larger context of global food security.
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Functional Sieve Element Protoplasts1[OA
Hafke, Jens B.; Furch, Alexandra C.U.; Reitz, Marco U.; van Bel, Aart J.E.
2007-01-01
Sieve element (SE) protoplasts were liberated by exposing excised phloem strands of Vicia faba to cell wall-degrading enzyme mixtures. Two types of SE protoplasts were found: simple protoplasts with forisome inclusions and composite twin protoplasts—two protoplasts intermitted by a sieve plate—of which one protoplast often includes a forisome. Forisomes are giant protein inclusions of SEs in Fabaceae. Membrane integrity of SE protoplasts was tested by application of CFDA, which was sequestered in the form of carboxyfluorescein. Further evidence for membrane intactness was provided by swelling of SE protoplasts and forisome dispersion in reaction to abrupt lowering of medium osmolarity. The absence of cell wall remnants as demonstrated by negative Calcofluor White staining allowed patch-clamp studies. At negative membrane voltages, the current-voltage relations of the SE protoplasts were dominated by a weak inward-rectifying potassium channel that was active at physiological membrane voltages of the SE plasma membrane. This channel had electrical properties that are reminiscent of those of the AKT2/3 channel family, localized in phloem cells of Arabidopsis (Arabidopsis thaliana). All in all, SE protoplasts promise to be a powerful tool in studying the membrane biology of SEs with inherent implications for the understanding of long-distance transport and signaling. PMID:17885083
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Oscillating scalar fields in extended quintessence
NASA Astrophysics Data System (ADS)
Li, Dan; Pi, Shi; Scherrer, Robert J.
2018-01-01
We study a rapidly oscillating scalar field with potential V (ϕ )=k |ϕ |n nonminimally coupled to the Ricci scalar R via a term of the form (1 -8 π G0ξ ϕ2)R in the action. In the weak coupling limit, we calculate the effect of the nonminimal coupling on the time-averaged equation of state parameter γ =(p +ρ )/ρ . The change in ⟨γ ⟩ is always negative for n ≥2 and always positive for n <0.71 (which includes the case where the oscillating scalar field could serve as dark energy), while it can be either positive or negative for intermediate values of n . Constraints on the time variation of G force this change to be infinitesimally small at the present time whenever the scalar field dominates the expansion, but constraints in the early universe are not as stringent. The rapid oscillation induced in G also produces an additional contribution to the Friedman equation that behaves like an effective energy density with a stiff equation of state, but we show that, under reasonable assumptions, this effective energy density is always smaller than the density of the scalar field itself.
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ERIC Educational Resources Information Center
Rossatto, César
2015-01-01
Masses of colonial workers are situating their free-for-all labor efforts in a global context due to dominant forms of organization based on a neoliberalist and corporate market economy. New social movements that show concern for democracy and human rights are challenging capitalist priorities of "efficiency" and exploitation. In some…
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Hu, Jiangyuan; Ferguson, Larissa; Adler, Kerry; Farah, Carole A; Hastings, Margaret H; Sossin, Wayne S; Schacher, Samuel
2017-07-10
Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same postsynaptic neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the postsynaptic neuron. A dominant-negative (dn) atypical PKM selectively reversed associative LTF, while a dn classical PKM selectively reversed non-associative LTF. Although both PKMs are formed from calpain-mediated cleavage of protein kinase C (PKC) isoforms, each form of LTF is sensitive to a distinct dn calpain expressed in the postsynaptic neuron. Associative LTF is blocked by dn classical calpain, whereas non-associative LTF is blocked by dn small optic lobe (SOL) calpain. Interfering with a putative synaptic tag, the adaptor protein KIBRA, which protects the atypical PKM from degradation, selectively erases associative LTF. Thus, the activity of distinct PRPs and tags in a postsynaptic neuron contribute to the maintenance of different forms of synaptic plasticity at separate inputs, allowing for selective reversal of synaptic plasticity and providing a cellular basis for developing therapeutic strategies for selectively reversing maladaptive memories. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Ancliff, P J; Gale, R E; Liesner, R; Hann, I M; Linch, D C
2001-11-01
Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Subsequently, autosomal dominant and sporadic forms of the disease have been recognized. All forms are manifest by persistent severe neutropenia and recurrent bacterial infection. In contrast, cyclical hematopoiesis is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, linkage analysis on 13 affected pedigrees identified chromosome 19p13.3 as the likely position for mutations in cyclical hematopoiesis. Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied. Further work also demonstrated mutations in ELA2 in sporadic and autosomal dominant SCN. However, all mutations described to date are heterozygous and thus appear to act in a dominant fashion, which is inconsistent with an autosomal recessive disease. Therefore, the current study investigated whether mutations in ELA2 could account for the disease phenotype in classical autosomal recessive SCN and in the sporadic and autosomal dominant types. All 5 exons of ELA2 and their flanking introns were studied in 18 patients (3 autosomal recessive, 5 autosomal dominant [from 3 kindreds], and 10 sporadic) using direct automated sequencing. No mutations were found in the autosomal recessive families. A point mutation was identified in 1 of 3 autosomal dominant families, and a base substitution was identified in 8 of 10 patients with the sporadic form, though 1 was subsequently shown to be a low-frequency polymorphism. These results suggest that mutations in ELA2 are not responsible for classical autosomal recessive Kostmann syndrome but provide further evidence for the role of ELA2 in SCN.
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NASA Astrophysics Data System (ADS)
Zeng, Yun-Chuan; Xu, Ji-Feng; Chen, Jian-Lin; Wang, Bao-Di; Kang, Zhi-Qiang; Huang, Feng
2018-02-01
The formation of the Shiquanhe-Yunzhug-Namu Tso ophiolite mélange zone (SNMZ) within the Lhasa Terrane, Tibetan Plateau, is key to understanding the Mesozoic tectonic evolution of this terrane, which remains controversial. We show that the Yunzhug ophiolite in the central segment of the SNMZ formed at 150 Ma, based on U-Pb dating of zircons from a gabbroic sample in a well-developed sheeted dike complex. Geochemically, these mafic rocks are dominated by E-MORB-type compositions, along with minor amounts of rocks with P-MORB-type compositions. The samples also exhibit high εNd(t) values and lack negative Nb and Ta anomalies. Data for all the samples plot within the MORB array on a Th/Yb-Nb/Yb diagram. Therefore, these mafic rocks most likely formed in either a slow spreading oceanic setting or an embryonic ocean, and not in a back-arc basin as has been previously assumed. Taking into account the regional geology, we propose that the Yunzhug ophiolite is part of a distinct ophiolitic belt and represents material formed in an embryonic ocean within the Lhasa Terrane, which provides new insights into the Jurassic tectonic evolution of the Lhasa Terrane.
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Self-organization of sorted patterned ground.
Kessler, M A; Werner, B T
2003-01-17
Striking circular, labyrinthine, polygonal, and striped patterns of stones and soil self-organize in many polar and high alpine environments. These forms emerge because freeze-thaw cycles drive an interplay between two feedback mechanisms. First, formation of ice lenses in freezing soil sorts stones and soil by displacing soil toward soil-rich domains and stones toward stone-rich domains. Second, stones are transported along the axis of elongate stone domains, which are squeezed and confined as freezing soil domains expand. In a numerical model implementing these feedbacks, circles, labyrinths, and islands form when sorting dominates; polygonal networks form when stone domain squeezing and confinement dominate; and stripes form as hillslope gradient is increased.
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Expression of a truncated Hmga1b gene induces gigantism, lipomatosis and B-cell lymphomas in mice.
Fedele, Monica; Visone, Rosa; De Martino, Ivana; Palmieri, Dario; Valentino, Teresa; Esposito, Francesco; Klein-Szanto, Andres; Arra, Claudio; Ciarmiello, Andrea; Croce, Carlo M; Fusco, Alfredo
2011-02-01
HMGA1 gene rearrangements have been frequently described in human lipomas. In vitro studies suggest that HMGA1 proteins have a negative role in the control of adipocyte cell growth, and that HMGA1 gene truncation acts in a dominant-negative fashion. Therefore, to define better the role of the HMGA1 alterations in the generation of human lipomas, we generated mice carrying an Hmga1b truncated (Hmga1b/T) gene. These mice develop a giant phenotype together with a drastic expansion of the retroperitoneal and subcutaneous white adipose tissue. We show that the activation of the E2F pathway likely accounts, at least in part, for this phenotype. Interestingly, the Hmga1b/T mice also develop B-cell lymphomas similar to that occurring in Hmga1-knockout mice, supporting a dominant-negative role of the Hmga1b/T mutant also in vivo. Copyright © 2010 Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Dilles, J. H.; Lee, R. G.; Wooden, J. L.; Koleszar, A. M.
2015-12-01
Porphyry Cu (Mo-Au) and epithermal Au-Ag ores are globally associated with shallow hydrous, strongly oxidized, and sulfur-rich arc intrusions. In many localities, long-lived magmatism includes evolution from early andesitic volcanic (v) and plutonic (p) rocks to later dacitic or rhyolitic compositions dominated by plutons. We compare zircon compositions from three igneous suites with different time spans: Yerington, USA (1 m.y., p>v), El Salvador, Chile (4 m.y., p>v), and Yanacocha, Peru (6 m.y., v>p). At Yerington granite dikes and ores formed in one event, at ES in 2 to 3 events spanning 3 m.y., and at Yanacocha in 6 events spanning 5 m.y. At both ES and Yanacocha, high-Al amphiboles likely crystallized at high temperature in the mid-crust and attest to deep magmas that periodically recharged the shallow chambers. At Yanacocha, these amphiboles contain anhydrite inclusions that require magmas were sulfur-rich and strongly oxidized (~NNO+2). The Ti-in-zircon geothermometer provides estimates of 920º to 620º C for zircon crystallization, and records both core to rim cooling and locally high temperature rim overgrowths. Ore-related silicic porphyries yield near-solidus crystallization temperatures of 750-650°C consistent with low zircon saturation temperatures. The latter zircons have large positive Ce/Ce* and small negative Eu/Eu*≥0.4 anomalies attesting to strongly oxidized conditions (Ballard et al., 2001), which we propose result from crystallization and SO2 loss to the magmatic-hydrothermal ore fluid (Dilles et al., 2015). The Hf, REE, Y, U, and Th contents of zircons are diverse in the magma suites, and Th/U vs Yb/Gd plots suggest a dominant role of crystal fractionation with lesser roles for both crustal contamination and mixing with high temperature deep-sourced mafic magma. Ce/Sm vs Yb/Gd plots suggest that magma REE contents at <900°C are dominated by early crystallization of hornblende and apatite, and late crystallization (~<780°C) of titanite. Magma mixing and crustal contamination are most evident in pre-ore magmas, whereas ore-forming intrusions at low temperatures are dominated by crystal fractionation. Thus, zircon provides evidence for cyclic crystallization and mafic recharge that enrich late silicic melts in incompatible ore components water, sulfur, chlorine and metals.
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Herberholz, Jens; Swierzbinski, Matthew E; Birke, Juliane M
2016-04-01
Like most social animals, crayfish readily form dominance relationships and linear social hierarchies when competing for limited resources. Competition often entails dyadic aggressive interactions, from which one animal emerges as the dominant and one as the subordinate. Once dominance relationships are formed, they typically remain stable for extended periods of time; thus, access to future resources is divided unequally among conspecifics. We previously showed that firmly established dominance relationships in juvenile crayfish can be disrupted by briefly adding a larger conspecific to the original pair. This finding suggested that the stability of social relationships in crayfish was highly context-dependent and more transient than previously assumed. We now report results that further identify the mechanisms underlying the destabilization of crayfish dominance relationships. We found that rank orders remained stable when conspecifics of smaller or equal size were added to the original pair, suggesting that both dominant and subordinate must be defeated by a larger crayfish in order to destabilize dominance relationships. We also found that dominance relationships remained stable when both members of the original pair were defeated by larger conspecifics in the absence of their original opponent. This showed that dominance relationships are not destabilized unless both animals experience defeat together. Lastly, we found that dominance relationships of pairs were successfully disrupted by larger intruders, although with reduced magnitude, after all chemical cues associated with earlier agonistic experiences were eliminated. These findings provide important new insights into the contextual features that regulate the stability of social dominance relationships in crayfish and probably in other species as well. © 2016 Marine Biological Laboratory.
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Susceptibility of Iα- and Iβ-Dominated Cellulose to TEMPO-Mediated Oxidation.
Carlsson, Daniel O; Lindh, Jonas; Strømme, Maria; Mihranyan, Albert
2015-05-11
The susceptibility of Iα- and Iβ-dominated cellulose to TEMPO-mediated oxidation was studied in this work since the cellulose Iα-allomorph is generally considered to be thermodynamically less stable and therefore more reactive than the cellulose Iβ-allomorph. Highly crystalline Cladophora nanocellulose, which is dominated by the Iα-allomorph, was oxidized to various degrees with TEMPO oxidant via bulk electrolysis in the absence of co-oxidants. Further, the Cladophora nanocellulose was thermally annealed in glycerol to produce its Iβ-dominated form and then oxidized. The produced materials were subsequently studied using FTIR, CP/MAS (13)C NMR, XRD, and SEM. The solid-state analyses confirmed that the annealed Cladophora cellulose was successfully transformed from an Iα- to an Iβ-dominated form. The results of the analyses of pristine and annealed TEMPO-oxidized samples suggest that Iα- and Iβ-dominated cellulose do not differ in susceptibility to TEMPO-oxidation. This work hence suggests that cellulose from different sources are not expected to differ in susceptibility to the oxidation due to differences in allomorph composition.
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Di Leva, Francesca; D'Adamo, Pio; Cubellis, Maria Vittoria; D'Eustacchio, Angela; Errichiello, Monica; Saulino, Claudio; Auletta, Gennaro; Giannini, Pasquale; Donaudy, Francesca; Ciccodicola, Alfredo; Gasparini, Paolo; Franzè, Annamaria; Marciano, Elio
2006-01-01
We ascertained a large Italian family with an autosomal dominant form of non-syndromic sensorineural hearing loss with vestibular involvement. A genome-wide scan found linkage to locus DFNA11. Sequencing of the MYO7A gene in the linked region identified a new missense mutation resulting in an Ala230Val change in the motor domain of the myosin VIIA. Myosin VIIA has already been implicated in several forms of deafness, but this is the third mutation causing a dominant form of deafness, located in the myosin VIIA motor domain in a region never involved in hearing loss until now. A modelled protein structure of myosin VII motor domain provides evidence for a significant functional effect of this missense mutation. Copyright (c) 2006 S. Karger AG, Basel.
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Negations in syllogistic reasoning: evidence for a heuristic-analytic conflict.
Stupple, Edward J N; Waterhouse, Eleanor F
2009-08-01
An experiment utilizing response time measures was conducted to test dominant processing strategies in syllogistic reasoning with the expanded quantifier set proposed by Roberts (2005). Through adding negations to existing quantifiers it is possible to change problem surface features without altering logical validity. Biases based on surface features such as atmosphere, matching, and the probability heuristics model (PHM; Chater & Oaksford, 1999; Wetherick & Gilhooly, 1995) would not be expected to show variance in response latencies, but participant responses should be highly sensitive to changes in the surface features of the quantifiers. In contrast, according to analytic accounts such as mental models theory and mental logic (e.g., Johnson-Laird & Byrne, 1991; Rips, 1994) participants should exhibit increased response times for negated premises, but not be overly impacted upon by the surface features of the conclusion. Data indicated that the dominant response strategy was based on a matching heuristic, but also provided evidence of a resource-demanding analytic procedure for dealing with double negatives. The authors propose that dual-process theories offer a stronger account of these data whereby participants employ competing heuristic and analytic strategies and fall back on a heuristic response when analytic processing fails.
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Willner, Dana L; Hugenholtz, Philip; Yerkovich, Stephanie T; Tan, Maxine E; Daly, Joshua N; Lachner, Nancy; Hopkins, Peter M; Chambers, Daniel C
2013-03-15
Bronchiolitis obliterans syndrome (BOS) is the primary limiting factor for long-term survival after lung transplantation, and has previously been associated with microbial infections. To cross-sectionally and longitudinally characterize microbial communities in allografts from transplant recipients with and without BOS using a culture-independent method based on high-throughput sequencing. Allografts were sampled by bronchoalveolar lavage, and microbial communities were profiled using 16S rRNA gene amplicon pyrosequencing. Community profiles were compared using the weighted Unifrac metric and the relationship between microbial populations, BOS, and other covariates was explored using PERMANOVA and logistic regression. Microbial communities in transplant patients fell into two main groups: those dominated by Pseudomonas or those dominated by Streptococcus and Veillonella, which seem to be mutually exclusive lung microbiomes. Aspergillus culture was also negatively correlated with the Pseudomonas-dominated group. The reestablishment of dominant populations present in patients pretransplant, notably Pseudomonas in individuals with cystic fibrosis, was negatively correlated with BOS. Recolonization of the allograft by Pseudomonas in individuals with cystic fibrosis is not associated with BOS. In general, reestablishment of pretransplant lung populations in the allograft seems to have a protective effect against BOS, whereas de novo acquisition of microbial populations often belonging to the same genera may increase the risk of BOS.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, J.C.; Lee, W.R.; Chang, S.H.
1992-01-01
To study mechanisms for dominance of phenotype, eight ENU- and four x-ray-induced mutations at the alcohol dehydrogenase (Adh) locus were analyzed for partial dominance in their interaction with normal alleles. All ENU and one of the x-ray mutations were single base substitutions; the other three x-ray mutations were 9-21 base deletions. All but one of the 12 mutant alleles were selected for this study because they produced detectable mutant polypeptides, but seven of the 11 producing a peptide could not form dimers with the normal peptide and the enzyme activity of heterozygotes was about half that of normal homozygotes. Fourmore » mutations formed dimers with a decreased catalytic efficiency and two of these were near the limit of detectability; these two also inhibited the formation of normal homodimers. The mutant alleles therefore show multiple mechanisms leading to partial enzyme expression in heterozygotes and a wide range of dominance ranging from almost complete recessive to nearly dominant. All amino acid changes in mutant peptides that form dimers are located between amino acids 182 and 194, so this region is not critical for dimerization. It may, however, be an important surface domain for catalyzation. 34 refs., 8 figs., 2 tabs.« less
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Grover, Sandeep; Fishman, Gerald A; Stone, Edwin M
2004-10-01
To define ophthalmic findings in a family with autosomal dominant retinitis pigmentosa and a novel IMPDH1 gene mutation. Genetic and observational family study. Sixteen affected members of a family with autosomal dominant retinitis pigmentosa. Ophthalmic examination, including best-corrected visual acuity (VA), slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, Goldmann kinetic perimetry, and electroretinography were performed. Deoxyribonucleic acid single-strand conformation polymorphism (SSCP) analysis was done. Abnormal polymerase chain reaction products identified by SSCP analysis were sequenced bidirectionally. All affected patients had the onset of night blindness within the first decade of life. Ocular findings were characterized by diffuse retinal pigmentary degenerative changes, marked restriction of peripheral visual fields, severe loss of VA, nondetectable electroretinography amplitudes, and a high frequency of posterior subcapsular lens opacities. Affected members were observed to harbor a novel IMPDH1 gene mutation. A novel IMPDH1 gene mutation (Arg231Pro) was associated with a severe form of autosomal dominant retinitis pigmentosa. Families affected with a severe form of this genetic subtype should be investigated for a mutation in the IMPDH1 gene.
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Activation of the JNK pathway is essential for transformation by the Met oncogene.
Rodrigues, G A; Park, M; Schlessinger, J
1997-05-15
The Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase is oncogenically activated through a rearrangement that creates a hybrid gene Tpr-Met. The resultant chimeric p65(Tpr-Met) protein is constitutively phosphorylated on tyrosine residues in vivo and associates with a number of SH2-containing signaling molecules including the p85 subunit of PI-3 kinase and the Grb2 adaptor protein, which couples receptor tyrosine kinases to the Ras signaling pathway. Mutation of the binding site for Grb2 impairs the ability of Tpr-Met oncoprotein to transform fibroblasts, suggesting that the activation of the Ras/MAP kinase signaling pathway through Grb2 may be essential for cellular transformation. To test this hypothesis dominant-negative mutants of Grb2 with deletions of the SH3 domains were introduced into Tpr-Met transformed fibroblasts. Cells overexpressing the mutants were found to be morphologically reverted and exhibited reduced growth in soft agar. Surprisingly, the Grb2 mutants blocked activation of the JNK/SAPK but not MAP kinase activity induced by the Tpr-Met oncoprotein. Additionally, cells expressing dominant-negative Grb2 mutants had reduced PI-3-kinase activity and dominant-negative mutants of Rac1 blocked both Tpr-Met-induced transformation and activation of JNK. These experiments reveal a novel link between Met and the JNK pathway, which is essential for transformation by this oncogene.
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Kloss, Christopher C; Lee, Jihyun; Zhang, Aaron; Chen, Fang; Melenhorst, Jan Joseph; Lacey, Simon F; Maus, Marcela V; Fraietta, Joseph A; Zhao, Yangbing; June, Carl H
2018-05-08
Cancer has an impressive ability to evolve multiple processes to evade therapies. While immunotherapies and vaccines have shown great promise, particularly in certain solid tumors such as prostate cancer, they have been met with resistance from tumors that use a multitude of mechanisms of immunosuppression to limit effectiveness. Prostate cancer, in particular, secretes transforming growth factor β (TGF-β) as a means to inhibit immunity while allowing for cancer progression. Blocking TGF-β signaling in T cells increases their ability to infiltrate, proliferate, and mediate antitumor responses in prostate cancer models. We tested whether the potency of chimeric antigen receptor (CAR) T cells directed to prostate-specific membrane antigen (PSMA) could be enhanced by the co-expression of a dominant-negative TGF-βRII (dnTGF-βRII). Upon expression of the dominant-negative TGF-βRII in CAR T cells, we observed increased proliferation of these lymphocytes, enhanced cytokine secretion, resistance to exhaustion, long-term in vivo persistence, and the induction of tumor eradication in aggressive human prostate cancer mouse models. Based on our observations, we initiated a phase I clinical trial to assess these CAR T cells as a novel approach for patients with relapsed and refractory metastatic prostate cancer (ClinicalTrials.gov: NCT03089203). Copyright © 2018. Published by Elsevier Inc.
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Tomshine, Jin C.; Severson, Sandra R.; Wigle, Dennis A.; Sun, Zhifu; Beleford, Daniah A. T.; Shridhar, Vijayalakshmi; Horazdovsky, Bruce F.
2009-01-01
Rin1 is a Rab5 guanine nucleotide exchange factor that plays an important role in Ras-activated endocytosis and growth factor receptor trafficking in fibroblasts. In this study, we show that Rin1 is expressed at high levels in a large number of non-small cell lung adenocarcinoma cell lines, including Hop62, H650, HCC4006, HCC827, EKVX, HCC2935, and A549. Rin1 depletion from A549 cells resulted in a decrease in cell proliferation that was correlated to a decrease in epidermal growth factor receptor (EGFR) signaling. Expression of wild type Rin1 but not the Rab5 guanine nucleotide exchange factor-deficient Rin1 (Rin1Δ) complemented the Rin1 depletion effects, and overexpression of Rin1Δ had a dominant negative effect on cell proliferation. Rin1 depletion stabilized the cell surface levels of EGFR, suggesting that internalization was necessary for robust signaling in A549 cells. In support of this conclusion, introduction of either dominant negative Rab5 or dominant negative dynamin decreased A549 proliferation and EGFR signaling. These data demonstrate that proper internalization and endocytic trafficking are critical for EGFR-mediated signaling in A549 cells and suggest that up-regulation of Rin1 in A549 cell lines may contribute to their proliferative nature. PMID:19570984
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Adolescent male chimpanzees do not form a dominance hierarchy with their peers.
Sandel, Aaron A; Reddy, Rachna B; Mitani, John C
2017-01-01
Dominance hierarchies are a prominent feature of the lives of many primate species. These hierarchies have important fitness consequences, as high rank is often positively correlated with reproduction. Although adult male chimpanzees strive for status to gain fitness benefits, the development of dominance relationships is not well understood. While two prior studies found that adolescent males do not display dominance relationships with peers, additional research at Ngogo in Kibale National Park, Uganda, indicates that adolescents there form a linear dominance hierarchy. These conflicting findings could reflect different patterns of rank acquisition across sites. An alternate possibility arises from a recent re-evaluation of age estimates at Ngogo and suggests that the report describing decided dominance relationships between adolescent males may have been due to the accidental inclusion of young adult males in the sample. To investigate these issues, we conducted a study of 23 adolescent male chimpanzees of known age during 12 months at Ngogo. Adolescent male chimpanzees exchanged pant grunts, a formal signal of submission, only 21 times. Recipients of pant grunts were late adolescent males, ranging between 14 and 16 years old. In contrast, younger adolescent males never received pant grunts from other males. Aggression between adolescent males was also rare. Analysis of pant grunts and aggressive interactions did not produce a linear dominance hierarchy among adolescent males. These data indicate that adolescent male chimpanzees do not form decided dominance relationships with their peers and are consistent with the hypothesis that the hierarchy described previously at Ngogo resulted from inaccurate age estimates of male chimpanzees. Because dominance relationships develop before adulthood in other primates, our finding that adolescent male chimpanzees do not do so is surprising. We offer possible explanations for why this is the case and suggest future studies that may help clarify the matter.
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Does water content or flow rate control colloid transport in unsaturated porous media?
Knappenberger, Thorsten; Flury, Markus; Mattson, Earl D; Harsh, James B
2014-04-01
Mobile colloids can play an important role in contaminant transport in soils: many contaminants exist in colloidal form, and colloids can facilitate transport of otherwise immobile contaminants. In unsaturated soils, colloid transport is, among other factors, affected by water content and flow rate. Our objective was to determine whether water content or flow rate is more important for colloid transport. We passed negatively charged polystyrene colloids (220 nm diameter) through unsaturated sand-filled columns under steady-state flow at different water contents (effective water saturations Se ranging from 0.1 to 1.0, with Se = (θ - θr)/(θs - θr)) and flow rates (pore water velocities v of 5 and 10 cm/min). Water content was the dominant factor in our experiments. Colloid transport decreased with decreasing water content, and below a critical water content (Se < 0.1), colloid transport was inhibited, and colloids were strained in water films. Pendular ring and water film thickness calculations indicated that colloids can move only when pendular rings are interconnected. The flow rate affected retention of colloids in the secondary energy minimum, with less colloids being trapped when the flow rate increased. These results confirm the importance of both water content and flow rate for colloid transport in unsaturated porous media and highlight the dominant role of water content.
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Davis, Timothy W; Bullerjahn, George S; Tuttle, Taylor; McKay, Robert Michael; Watson, Susan B
2015-06-16
Sandusky Bay experiences annual toxic cyanobacterial blooms dominated by Planktothrix agardhii/suspensa. To further understand the environmental drivers of these events, we evaluated changes in the growth response and toxicity of the Planktothrix-dominated blooms to nutrient amendments with orthophosphate (PO4) and inorganic and organic forms of dissolved nitrogen (N; ammonium (NH4), nitrate (NO3) and urea) over the bloom season (June - October). We complemented these with a metagenomic analysis of the planktonic microbial community. Our results showed that bloom growth and microcystin (MC) concentrations responded more frequently to additions of dissolved N than PO4, and that the dual addition of NH4 + PO4 and Urea + PO4 yielded the highest MC concentrations in 54% of experiments. Metagenomic analysis confirmed that P. agardhii/suspensa was the primary MC producer. The phylogenetic distribution of nifH revealed that both heterocystous cyanobacteria and heterotrophic proteobacteria had the genetic potential for N2 fixation in Sandusky Bay. These results suggest that as best management practices are developed for P reductions in Sandusky Bay, managers must be aware of the negative implications of not managing N loading into this system as N may significantly impact cyanobacterial bloom size and toxicity.
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NASA Astrophysics Data System (ADS)
Pan, Jie; Cheng, Yang-Tse; Qi, Yue
2015-04-01
Understanding the ionic conduction in solid electrolytes in contact with electrodes is vitally important to many applications, such as lithium ion batteries. The problem is complex because both the internal properties of the materials (e.g., electronic structure) and the characteristics of the externally contacting phases (e.g., voltage of the electrode) affect defect formation and transport. In this paper, we developed a method based on density functional theory to study the physics of defects in a solid electrolyte in equilibrium with an external environment. This method was then applied to predict the ionic conduction in lithium fluoride (LiF), in contact with different electrodes which serve as reservoirs with adjustable Li chemical potential (μLi) for defect formation. LiF was chosen because it is a major component in the solid electrolyte interphase (SEI) formed on lithium ion battery electrodes. Seventeen possible native defects with their relevant charge states in LiF were investigated to determine the dominant defect types on various electrodes. The diffusion barrier of dominant defects was calculated by the climbed nudged elastic band method. The ionic conductivity was then obtained from the concentration and mobility of defects using the Nernst-Einstein relationship. Three regions for defect formation were identified as a function of μLi: (1) intrinsic, (2) transitional, and (3) p -type region. In the intrinsic region (high μLi, typical for LiF on the negative electrode), the main defects are Schottky pairs and in the p -type region (low μLi, typical for LiF on the positive electrode) are Li ion vacancies. The ionic conductivity is calculated to be approximately 10-31Scm-1 when LiF is in contact with a negative electrode but it can increase to 10-12Scm-1 on a positive electrode. This insight suggests that divalent cation (e.g., Mg2+) doping is necessary to improve Li ion transport through the engineered LiF coating, especially for LiF on negative electrodes. Our results provide an understanding of the influence of the environment on defect formation and demonstrate a linkage between defect concentration in a solid electrolyte and the voltage of the electrode.
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Electrospray ionization of uranyl-citrate complexes
NASA Astrophysics Data System (ADS)
Somogyi, Árpád; Pasilis, Sofie P.; Pemberton, Jeanne E.
2007-09-01
Results presented here demonstrate the usefulness of electrospray ionization and gas-phase ion-molecule reactions to predict structural and electronic differences in complex inorganic ions. Electrospray ionization of uranyl citrate solutions generates positively and negatively charged ions that participate in further ion-molecule reactions in 3D ion trap and FT-ICR mass analyzers. Most ions observed are derived from the major solution uranyl-citrate complexes and involve species of {(UO2)2Cit2}2-, (UO2)3Cit2, and {(UO2)3Cit3}3-, where Cit indicates the citrate trianion, C6H5O73-. In a 3D ion trap operated at relatively high pressure, complex adducts containing solvent molecules, alkali and ammonium cations, and nitrate or chloride anions are dominant, and proton/alkali cation (Na+, K+) exchange is observed for up to six exchangeable protons in an excess of alkali cations. Adduct formation in a FT-ICR cell that is operated at lower pressures is less dominant, and direct detection of positive and negative ions of the major solution complexes is possible. Multiply charged ions are also detected, suggesting the presence of uranium in different oxidation states. Changes in uranium oxidation state are detected by He-CID and SORI-CID fragmentation, and certain fragments undergo association reactions in trapping analyzers, forming "exotic" species such as [(UO2)4O3]-, [(UO2)4O4]-, and [(UO2)4O5]-. Ion-molecule reactions with D2O in the FT-ICR cell indicate substantial differences in H/D exchange rate and D2O accommodation for different ion structures and charge states. Most notably, the positively charged ions [H2(UO2)2Cit2(H)]+ and [(UO2)2(Cit)]+ accommodate two and three D2O molecules, respectively, which reflects well the structural differences, i.e., tighter uranyl-citrate coordination in the former ion than in the latter. The corresponding negatively charged ions accommodate zero or two D2O molecules, which can be rationalized using suggested solution phase structures and charge state distributions.
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Johnson, R N; Oldroyd, B P; Barron, A B; Crozier, R H
2002-01-01
We studied the genetic control of the dance dialects that exist in the different subspecies of honey bees (Apis mellifera) by observing the variation in dance form observed in a backcross between two lines that showed widely different dance dialects. To do this we generated the reciprocal of the cross performed by Rinderer and Beaman (1995), thus producing phenotypic segregation of dance forms within a single colony rather than between colonies. Our results are consistent with Rinderer and Beaman (1995) in that inheritance of the transition point from round dancing --> waggle dancing is consistent with control by a single locus with more than one allele. That is, we found one dance type to be dominant in the F(1), and observed a 1:1 segregation of dance in a backcross involving the F(1) and the recessive parent. However, we found some minor differences in dance dialect inheritance, with the most significant being an apparent reversal of dominance between our cross (for us "black" is the dominant dialect) and that of Rinderer and Beaman (1995) (they report "yellow" to be the dominant dialect). We also found that our black bees do not perform a distinct sickle dance, whereas the black bees used by Rinderer and Beaman (1995) did perform such a dance. However, our difference in dominance need not contradict the results of Rinderer and Beaman (1995), as there is no evidence that body color and dominance for dance dialect are linked.
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Compassionate Love Buffers Stress-Reactive Mothers From Fight-or-Flight Parenting
Miller, Jonas G.; Kahle, Sarah; Lopez, Monica; Hastings, Paul D.
2015-01-01
The links among mothers’ compassionate love for their child, autonomic nervous system activity, and parenting behavior during less and more challenging mother–child interactions were examined. Mothers expressed and reported less negative affect when they exhibited autonomic patterns of increased parasympathetic dominance (high parasympathetic and low sympathetic activation) or autonomic coactivation (high parasympathetic and high sympathetic activation) during the less challenging interaction and autonomic coactivation during the more challenging interaction. Compassionate love predicted less reported and observed negativity in mothers who showed increased sympathetic nervous system dominance (high sympathetic and low parasympathetic activation). Compassionate love appeared to help mothers, and particularly those who experienced strong physiological arousal during difficult parenting situations, establish positive socialization contexts for their children and avoid stress-induced adverse parenting. PMID:25329554
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Billiard, Sylvain; Castric, Vincent; Vekemans, Xavier
2007-03-01
We developed a general model of sporophytic self-incompatibility under negative frequency-dependent selection allowing complex patterns of dominance among alleles. We used this model deterministically to investigate the effects on equilibrium allelic frequencies of the number of dominance classes, the number of alleles per dominance class, the asymmetry in dominance expression between pollen and pistil, and whether selection acts on male fitness only or both on male and on female fitnesses. We show that the so-called "recessive effect" occurs under a wide variety of situations. We found emerging properties of finite population models with several alleles per dominance class such as that higher numbers of alleles are maintained in more dominant classes and that the number of dominance classes can evolve. We also investigated the occurrence of homozygous genotypes and found that substantial proportions of those can occur for the most recessive alleles. We used the model for two species with complex dominance patterns to test whether allelic frequencies in natural populations are in agreement with the distribution predicted by our model. We suggest that the model can be used to test explicitly for additional, allele-specific, selective forces.
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Isojima, Tsuyoshi; Ishizawa, Michiyasu; Yoshimura, Kazuko; Tamura, Mayuko; Hirose, Shinichi; Makishima, Makoto; Kitanaka, Sachiko
2015-06-01
Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the VDR gene, and its inheritance is autosomal recessive. In this report, we aimed to confirm whether HVDRR is occasionally inherited as a dominant trait. An 18-month-old Japanese boy was evaluated for short stature and bowlegs. His father had been treated for rickets during childhood, and his paternal grandfather had bowlegs. We diagnosed him with HVDRR based on laboratory data and radiographic evidence of rickets. Sequence analyses of VDR were performed, and the functional consequences of the detected mutations were analyzed for transcriptional activity, ligand binding, and interaction with the retinoid X receptor, cofactors, and the vitamin D response element (VDRE). A novel mutation (Q400LfsX7) and a reported variant (R370H) were identified in the patient. Heterozygous Q400LfsX7 was detected in his father, and heterozygous R370H was detected in his healthy mother. Functional studies revealed that the transcriptional activity of Q400LfsX7-VDR was markedly disturbed. The mutant had a dominant-negative effect on wild-type-VDR, and the ligand binding affinity of Q400LfsX7-VDR was completely impaired. Interestingly, Q400LfsX7-VDR had a strong interaction with corepressor NCoR and could interact with VDRE without the ligand. R370H-VDR was functionally similar to wild-type-VDR. In conclusion, we found a dominant-negative mutant of VDR causing dominantly inherited HVDRR through a constitutive corepressor interaction, a mechanism similar to that in dominantly inherited thyroid hormone receptor mutations. Our report together with a reported pedigree suggested a distinct inheritance of HVDRR and enriched our understanding of VDR abnormalities.
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A study of the geomagnetic indices asymmetry based on the interplanetary magnetic field polarities
NASA Astrophysics Data System (ADS)
El-Borie, M. A.; El-Taher, A. M.; Aly, N. E.; Bishara, A. A.
2018-05-01
Data of geomagnetic indices ( aa, Kp, Ap, and Dst) recorded near 1 AU over the period 1967-2016, have been studied based on the asymmetry between the interplanetary magnetic field (IMF) directions above and below of the heliospheric current sheet (HCS). Our results led to the following conclusions: (i) Throughout the considered period, 31 random years (62%) showed apparent asymmetries between Toward (T) and Away (A) polarity days and 19 years (38%) exhibited nearly a symmetrical behavior. The days of A polarity predominated over the T polarity days by 4.3% during the positive magnetic polarity epoch (1991-1999). While the days of T polarity exceeded the days of A polarity by 5.8% during the negative magnetic polarity epoch (2001-2012). (ii) Considerable yearly North-South (N-S) asymmetries of geomagnetic indices observed throughout the considered period. (iii) The largest toward dominant peaks for aa and Ap indices occurred in 1995 near to minimum of solar activity. Moreover, the most substantial away dominant peaks for aa and Ap indices occurred in 2003 (during the descending phase of the solar cycle 23) and in 1991 (near the maximum of solar activity cycle) respectively. (iv) The N-S asymmetry of Kp index indicated a most significant away dominant peak occurred in 2003. (v) Four of the away dominant peaks of Dst index occurred at the maxima of solar activity in the years 1980, 1990, 2000, and 2013. The largest toward dominant peak occurred in 1991 (at the reversal of IMF polarity). (vi) The geomagnetic indices ( aa, Ap, and Kp) all have northern dominance during positive magnetic polarity epoch (1971-1979), while the asymmetries shifts to the southern solar hemisphere during negative magnetic polarity epoch (2001-2012).
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Veldwijk, Jorien; Essers, Brigitte A B; Lambooij, Mattijs S; Dirksen, Carmen D; Smit, Henriette A; de Wit, G Ardine
2016-01-01
To test how attribute framing in a discrete choice experiment (DCE) affects respondents' decision-making behavior and their preferences. Two versions of a DCE questionnaire containing nine choice tasks were distributed among a representative sample of the Dutch population aged 55 to 65 years. The DCE consisted of four attributes related to the decision regarding participation in genetic screening for colorectal cancer (CRC). The risk attribute included was framed positively as the probability of surviving CRC and negatively as the probability of dying from CRC. Panel mixed-logit models were used to estimate the relative importance of the attributes. The data of the positively and negatively framed DCE were compared on the basis of direct attribute ranking, dominant decision-making behavior, preferences, and importance scores. The majority (56%) of the respondents ranked survival as the most important attribute in the positively framed DCE, whereas only a minority (8%) of the respondents ranked mortality as the most important attribute in the negatively framed DCE. Respondents made dominant choices based on survival significantly more often than based on mortality. The framing of the risk attribute significantly influenced all attribute-level estimates and resulted in different preference structures among respondents in the positively and negatively framed data set. Risk framing affects how respondents value the presented risk. Positive risk framing led to increased dominant decision-making behavior, whereas negative risk framing led to risk-seeking behavior. Attribute framing should have a prominent part in the expert and focus group interviews, and different types of framing should be used in the pilot version of DCEs as well as in actual DCEs to estimate the magnitude of the effect of choosing different types of framing. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
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Climate-driven disparities among ecological interactions threaten kelp forest persistence.
Provost, Euan J; Kelaher, Brendan P; Dworjanyn, Symon A; Russell, Bayden D; Connell, Sean D; Ghedini, Giulia; Gillanders, Bronwyn M; Figueira, WillIAM; Coleman, Melinda A
2017-01-01
The combination of ocean warming and acidification brings an uncertain future to kelp forests that occupy the warmest parts of their range. These forests are not only subject to the direct negative effects of ocean climate change, but also to a combination of unknown indirect effects associated with changing ecological landscapes. Here, we used mesocosm experiments to test the direct effects of ocean warming and acidification on kelp biomass and photosynthetic health, as well as climate-driven disparities in indirect effects involving key consumers (urchins and rock lobsters) and competitors (algal turf). Elevated water temperature directly reduced kelp biomass, while their turf-forming competitors expanded in response to ocean acidification and declining kelp canopy. Elevated temperatures also increased growth of urchins and, concurrently, the rate at which they thinned kelp canopy. Rock lobsters, which are renowned for keeping urchin populations in check, indirectly intensified negative pressures on kelp by reducing their consumption of urchins in response to elevated temperature. Overall, these results suggest that kelp forests situated towards the low-latitude margins of their distribution will need to adapt to ocean warming in order to persist in the future. What is less certain is how such adaptation in kelps can occur in the face of intensifying consumptive (via ocean warming) and competitive (via ocean acidification) pressures that affect key ecological interactions associated with their persistence. If such indirect effects counter adaptation to changing climate, they may erode the stability of kelp forests and increase the probability of regime shifts from complex habitat-forming species to more simple habitats dominated by algal turfs. © 2016 John Wiley & Sons Ltd.
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Identification of Key Interactions in the Initial Self-Assembly of Amylin in a Membrane Environment.
Christensen, Mikkel; Skeby, Katrine K; Schiøtt, Birgit
2017-09-12
Islet amyloid polypeptide, also known as amylin, forms aggregates that reduce the amount of insulin-producing cells in patients with type II diabetes mellitus. Much remains unknown about the process of aggregation and cytotoxicity, but it is known that certain cell membrane components can alter the rate of aggregation. Using atomistic molecular dynamics simulations combined with the highly mobile membrane mimetic model incorporating enhanced sampling of lipid diffusion, we investigate interaction of amylin peptides with the membrane components as well as the self-assembly of amylin. Consistent with experimental evidence, we find that an initial membrane-bound α-helical state folds into stable β-sheet structures upon self-assembly. Our results suggest the following mechanism for the initial phase of amylin self-assembly. The peptides move around on the membrane with the positively charged N-terminus interacting with the negatively charged lipid headgroups. When the peptides start to interact, they partly unfold and break some of the contacts with the membrane. The initial interactions between the peptides are dominated by aromatic and hydrophobic interactions. Oligomers are formed showing both intra- and interpeptide β-sheets, initially with interactions mainly in the C-terminal domain of the peptides. Decreasing the pH to 5.5 is known to inhibit amyloid formation. At low pH, His18 is protonated, adding a fourth positive charge at the peptide. With His18 protonated, no oligomerization is observed in the simulations. The additional charge gives a strong midpoint anchoring of the peptides to negatively charged membrane components, and the peptides experience additional interpeptide repulsion, thereby preventing interactions.
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Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hirata, Yuki; Choi, Junho, E-mail: choi@mech.t.u-tokyo.ac.jp
2015-08-28
Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from −1.0 to −15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) andmore » Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a deviation from the Raman behavior of a-C:H films deposited by bipolar PBII&D. This tendency intensifies as the negative voltage becomes greater. Also, the energy of incident ions on the sidewall of the trench increases with increasing negative voltage, which causes a shift in the Raman data of the sidewall to the bottom right corner on the figure depicting the relationship of the FWHM(G) and the G-peak position, indicating increased graphitization of a-C:H film.« less
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Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior
NASA Astrophysics Data System (ADS)
Hirata, Yuki; Choi, Junho
2015-08-01
Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from -1.0 to -15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a deviation from the Raman behavior of a-C:H films deposited by bipolar PBII&D. This tendency intensifies as the negative voltage becomes greater. Also, the energy of incident ions on the sidewall of the trench increases with increasing negative voltage, which causes a shift in the Raman data of the sidewall to the bottom right corner on the figure depicting the relationship of the FWHM(G) and the G-peak position, indicating increased graphitization of a-C:H film.
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Cooling field and temperature dependent exchange bias in Gd substituted YFe0.5Cr0.5O3
NASA Astrophysics Data System (ADS)
Singh, Karan; Mukherjee, K.
2018-04-01
We report the results of our investigation of cooling field and temperature dependence of exchange bias on Gd substituted mixed metal oxide YFe0.5Cr0.5O3. A negative exchange bias is observed in the Gd-substituted compounds, in contrast to the positive exchange bias in parent compound, YFe0.5Cr0.5O3 [1]. With the increase in Gd concentration it is noted that the exchange bias decreases. It was noted that the paramagnetic contribution from Gd ions plays the leading role in comparison to the antiferromagnetic type correlations among spins as is observed for the parent compound. Due to magnetic rare earth ion, additional exchange interaction of the form Gd-O-Fe/Cr dominates the magnetic interaction arising due to the transition metal ions, resulting in the reduction in exchange bias value.
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Zheng, Yulong; Liao, Zhiyong
2017-11-22
Invasive plant species often form dense mono-dominant stands in areas they have invaded, while having only sparse distribution in their native ranges, and the reasons behind this phenomenon are a key point of research in invasive species biology. Differences in species composition between native and invasive ranges may contribute to the difference in distribution status. In this study, we found that the high-density condition had a more negative effect on C. odorata than the low-density condition when co-grown with neighbor plants from its native range in Mexico, while this pattern was not in evidence when it was grown with neighbors from its invasive range in China. Different competitive ability and coevolutionary history with C. odorata between native-range neighbors and invasive-range neighbors may lead to the inconsistent patterns.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Carelli, F.; Grassi, T.; Gianturco, F. A.
The elementary mechanisms through which molecular polyynes could form stable negative ions after interacting with free electrons in planetary atmospheres (e.g., Titan's) are analyzed using quantum scattering calculations and quantum structure methods. The case of radical species and of nonpolar partners are analyzed via specific examples for both the C{sub n}H and HC{sub n}H series, with n values from 4 to 12. We show that attachment processes to polar radicals are dominating the anionic production and that the mediating role of dipolar scattering states is crucial to their formation. The corresponding attachment rates are presented as calculated upper limits tomore » their likely values and are obtained down to the low temperatures of interest. The effects of the computed rates, when used in simple evolutionary models, are also investigated and presented in detail.« less
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Manno, Jack P
2010-01-01
Commoditization is a generalized Darwinian selection pressure in economic evolution driven by profit- and efficiency-seeking in the investment of key resources. By winnowing noncommodity opportunities to satisfy human needs, commoditization distorts development in ways that intensify negative social outcomes experienced by oppressed groups and undermines the possibility for sustainable development. When market logic dominates the investment of financial capital, energy, raw materials, human attention, labor, and creativity, market goods with traits associated with commodities are fully developed while nonmarket goods lacking those traits are systematically underdeveloped. Analysis of the traits of commodities explains the unsustainable development or maldevelopment that disproportionately affects those who are dependent on or who highly value important nonmarket relationships. Oppression theory is addressed with specific examples. A generalized form of oppression is theorized that systematically stunts the imagination and creativity required to meet contemporary environmental crises.
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Functional association of Sun1 with nuclear pore complexes
Liu, Qian; Pante, Nelly; Misteli, Tom; Elsagga, Mohamed; Crisp, Melissa; Hodzic, Didier; Burke, Brian; Roux, Kyle J.
2007-01-01
Sun1 and 2 are A-type lamin-binding proteins that, in association with nesprins, form a link between the inner nuclear membranes (INMs) and outer nuclear membranes of mammalian nuclear envelopes. Both immunofluorescence and immunoelectron microscopy reveal that Sun1 but not Sun2 is intimately associated with nuclear pore complexes (NPCs). Topological analyses indicate that Sun1 is a type II integral protein of the INM. Localization of Sun1 to the INM is defined by at least two discrete regions within its nucleoplasmic domain. However, association with NPCs is dependent on the synergy of both nucleoplasmic and lumenal domains. Cells that are either depleted of Sun1 by RNA interference or that overexpress dominant-negative Sun1 fragments exhibit clustering of NPCs. The implication is that Sun1 represents an important determinant of NPC distribution across the nuclear surface. PMID:17724119
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Brooks, Benjamin
2008-01-01
Small to Medium Sized Enterprises (SMEs) form the majority of Australian businesses. This study uses ethnographic research methods to describe the organizational culture of a small furniture-manufacturing business in southern Australia. Results show a range of cultural assumptions variously 'embedded' within the enterprise. In line with memetics - Richard Dawkin's cultural application of Charles Darwin's theory of Evolution by Natural Selection, the author suggests that these assumptions compete to be replicated and retained within the organization. The author suggests that dominant assumptions are naturally selected, and that the selection can be better understood by considering the cultural assumptions in reference to Darwin's original principles and Frederik Barth's anthropological framework of knowledge. The results are discussed with reference to safety systems, negative cultural elements called Cultural Safety Viruses, and how our understanding of this particular organizational culture might be used to build resistance to these viruses.
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Wolfe, Benjamin E.; Button, Julie E.; Santarelli, Marcela; Dutton, Rachel J.
2014-01-01
SUMMARY Tractable microbial communities are needed to bridge the gap between observations of patterns of microbial diversity and mechanisms that can explain these patterns. We developed cheese rinds as model microbial communities by characterizing in situ patterns of diversity and by developing an in vitro system for community reconstruction. Sequencing of 137 different rind communities across 10 countries revealed 24 widely distributed and culturable genera of bacteria and fungi as dominant community members. Reproducible community types formed independent of geographic location of production. Intensive temporal sampling demonstrated that assembly of these communities is highly reproducible. Patterns of community composition and succession observed in situ can be recapitulated in a simple in vitro system. Widespread positive and negative interactions were identified between bacterial and fungal community members. Cheese rind microbial communities represent an experimentally tractable system for defining mechanisms that influence microbial community assembly and function. PMID:25036636
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NASA Astrophysics Data System (ADS)
Li, Wei; Wang, Tian-Xing; Dai, Xian-Qi; Wang, Xiao-Long; Ma, Ya-Qiang; Chang, Shan-Shan; Tang, Ya-Nan
2017-04-01
Using density functional theory calculations, we investigate the electronic properties of arsenene/graphene van der Waals (vdW) heterostructures by applying external electric field perpendicular to the layers. It is demonstrated that weak vdW interactions dominate between arsenene and graphene with their intrinsic electronic properties preserved. We find that an n-type Schottky contact is formed at the arsenene/graphene interface with a Schottky barrier of 0.54 eV. Moreover, the vertical electric field can not only control the Schottky barrier height but also the Schottky contacts (n-type and p-type) and Ohmic contacts (n-type) at the interface. Tunable p-type doping in graphene is achieved under the negative electric field because electrons can transfer from the Dirac point of graphene to the conduction band of arsenene. The present study would open a new avenue for application of ultrathin arsenene/graphene heterostructures in future nano- and optoelectronics.
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NASA Astrophysics Data System (ADS)
Rebelo, André; Cunha, Tiago; Mendes, Mónica; da Silva, Filipe Ferreira; García, Gustavo; Limão-Vieira, Paulo
2016-06-01
Kinetic-energy release distributions have been obtained from the width and shapes of the time-of-flight (TOF) negative ion mass peaks formed in collisions of fast potassium atoms with D-Ribose (DR) and tetrahydrofuran (THF) molecules. Recent dissociative ion-pair formation experiments yielding anion formation have shown that the dominant fragment from D-Ribose is OH- [D. Almeida, F. Ferreira da Silva, G. García, P. Limão-Vieira, J. Chem. Phys. 139, 114304 (2013)] whereas in the case of THF is O- [D. Almeida, F. Ferreira da Silva, S. Eden, G. García, P. Limão-Vieira, J. Phys. Chem. A 118, 690 (2014)]. The results for DR and THF show an energy distribution profile reminiscent of statistical degradation via vibrational excitation and partly due to direct transformation of the excess energy in translational energy.
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Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.
Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto
2003-12-01
There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest genetic cascade. In order to study the hierarchical relationship between msx1 and snail/slug we performed several rescue experiments using dominant negatives for these genes. The rescuing activity by snail and slug on neural crest development of the msx1 dominant negative, together with the inability of msx1 to rescue the dominant negatives of slug and snail strongly argue that msx1 is upstream of snail and slug in the genetic cascade that specifies the neural crest in the ectoderm. We propose a model where a gradient of Bmp activity specifies the expression of Msx genes in the neural folds, and that this expression is essential for the early specification of the neural crest.
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Jones, Adele M; Xue, Youjia; Kinsela, Andrew S; Wilcken, Klaus M; Collins, Richard N
2016-03-15
Donnan dialysis has been applied to forty filtered drainage waters collected from five coastal lowland acid sulfate soil (CLASS) catchments across north-eastern NSW, Australia. Despite having average pH values<3.9, 78 and 58% of Al and total Fe, respectively, were present as neutral or negatively-charged species. Complementary isotope dilution experiments with (55)Fe and (26)Al demonstrated that only soluble (i.e. no colloidal) species were present. Trivalent rare earth elements (REEs) were also mainly present (>70%) as negatively-charged complexes. In contrast, the speciation of the divalent trace metals Co, Mn, Ni and Zn was dominated by positively-charged complexes and was strongly correlated with the alkaline earth metals Ca and Mg. Thermodynamic equilibrium speciation calculations indicated that natural organic matter (NOM) complexes dominated Fe(III) speciation in agreement with that obtained by Donnan dialysis. In the case of Fe(II), however, the free cation was predicted to dominate under thermodynamic equilibrium, whilst our results indicated that Fe(II) was mainly present as neutral or negatively-charged complexes (most likely with sulfate). For all other divalent metals thermodynamic equilibrium speciation calculations agreed well with the Donnan dialysis results. The proportion of Al and REEs predicted to be negatively-charged was also grossly underestimated, relative to the experimental results, highlighting possible inaccuracies in the stability constants developed for these trivalent Me(SO4)2(-) and/or Me-NOM complexes and difficulties in modeling complex environmental samples. These results will help improve metal mobility and toxicity models developed for CLASS-affected environments, and also demonstrate that Australian CLASS environments can discharge REEs at concentrations an order of magnitude greater than previously reported. Copyright © 2015 Elsevier B.V. All rights reserved.
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An exposition on Friedmann cosmology with negative energy densities
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nemiroff, Robert J.; Joshi, Ravi; Patla, Bijunath R., E-mail: nemiroff@mtu.edu, E-mail: rjoshimtu@gmail.com, E-mail: bijunath.patla@nist.gov
2015-06-01
How would negative energy density affect a classic Friedmann cosmology? Although never measured and possibly unphysical, certain realizations of quantum field theories leaves the door open for such a possibility. In this paper we analyze the evolution of a universe comprising varying amounts of negative energy forms. Negative energy components have negative normalized energy densities, Ω < 0. They include negative phantom energy with an equation of state parameter w < −1, negative cosmological constant: w=−1, negative domain walls: w = −2/3, negative cosmic strings: w=−1/3, negative mass: w = 0, negative radiation: w = 1/3 and negative ultralight: w > 1/3. Assuming that such energy forms generate pressure like perfect fluids,more » the attractive or repulsive nature of negative energy components are reviewed. The Friedmann equation is satisfied only when negative energy forms are coupled to a greater magnitude of positive energy forms or positive curvature. We show that the solutions exhibit cyclic evolution with bounces and turnovers.The future and fate of such universes in terms of curvature, temperature, acceleration, and energy density are reviewed. The end states are dubbed ''big crunch,' '' big void,' or ''big rip' and further qualified as ''warped',''curved', or ''flat',''hot' versus ''cold', ''accelerating' versus ''decelerating' versus ''coasting'. A universe that ends by contracting to zero energy density is termed ''big poof.' Which contracting universes ''bounce' in expansion and which expanding universes ''turnover' into contraction are also reviewed.« less
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Dominant-negative diabetes insipidus and other endocrinopathies
Phillips, John A.
2003-01-01
Familial neurohypophyseal diabetes insipidus (FNDI) in humans is an autosomal dominant disorder caused by a variety of mutations in the arginine vasopressin (AVP) precursor. A new report demonstrates how heterozygosity for an AVP mutation causes FNDI (see the related article beginning on page 1697). Using an AVP knock-in mutation in mice, the study shows that FNDI is caused by retention of AVP precursors and progressive loss of AVP-producing neurons. PMID:14660740
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Richard E. Feldman; Pam G. Krannitz
2005-01-01
The Garry oak (Quercus garryana) ecosystem was once a dominant habitat type on southeastern Vancouver Island, British Columbia, but urbanization has lead to massive habitat loss and fragmentation (Hebda 1993). Most bird species are expected to respond negatively to urbanization because of increased patch isolation, increased predation pressure, and negative edge...
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NASA Astrophysics Data System (ADS)
Nosouhian, N.; Torabi, G.; Arai, S.
2016-05-01
Late Cretaceous Bayazeh dyke swarm is situated in the western part of the Central-East Iranian Microcontinent (CEIM). These dykes with a dominant northeast-southwest trend occur in the Eastern margin of the Yazd block. They cross cut the Lower Cretaceous sedimentary rocks. The length of the Bayazeh dykes occasionally reaches up to the 2 km. Rock forming minerals of these dykes are plagioclase (andesine and oligoclase), amphibole (magnesio-hastingsitic hornblende, magnesio-hornblende and tschermakitic hornblende), quartz, K-feldspar (orthoclase), zircon and apatite. Secondary minerals are chlorite (pycnochlorite), albite, magnetite and calcite. The main textures are porphyritic, glomeroporphyritic and poikilitic. The felsic character of the Bayazeh dacitic dykes is shown by their high SiO2 (62.70 to 64.60 wt %) and low [Fe2O3* + MgO + MnO + TiO2] (average 4.64 wt %) contents. These dykes represent the peraluminous to metaluminous nature and their Na2O and K2O values are 5.20-7.14 and 1.51-2.59 wt %, respectively, which reveal their sodic chemistry. The trace element characteristics are the LREE enrichment relative to HREE, [La/Yb]CN = 13.27-22.99, and slightly negative or positive Eu anomaly. These geochemical characteristics associated with low Nb/La (0.16-0.25), Yb/Nd (0.04-0.05) and high Zr/Sm (37.60-58.25) ratios indicate that the melting of a metamorphosed subducted oceanic crust is occurred where the residual mineral assemblage is dominated by garnet amphibolite. The chemical compositions of the Bayazeh dykes resemble those of slab-derived tonalite-trondhjemite-granodiorite (TTG) series. They were formed by subduction of Mesozoic Neo-Tethys -related Nain and Ashin oceanic crusts.
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Zhang, Qian; Yang, Ruyi; Tang, Jianjun; Yang, Haishui; Hu, Shuijin; Chen, Xin
2010-08-24
Negative or positive feedback between arbuscular mycorrhizal fungi (AMF) and host plants can contribute to plant species interactions, but how this feedback affects plant invasion or resistance to invasion is not well known. Here we tested how alterations in AMF community induced by an invasive plant species generate feedback to the invasive plant itself and affect subsequent interactions between the invasive species and its native neighbors. We first examined the effects of the invasive forb Solidago canadensis L. on AMF communities comprising five different AMF species. We then examined the effects of the altered AMF community on mutualisms formed with the native legume forb species Kummerowia striata (Thunb.) Schindl. and on the interaction between the invasive and native plants. The host preferences of the five AMF were also assessed to test whether the AMF form preferred mutualistic relations with the invasive and/or the native species. We found that S. canadensis altered AMF spore composition by increasing one AMF species (Glomus geosporum) while reducing Glomus mosseae, which is the dominant species in the field. The host preference test showed that S. canadensis had promoted the abundance of AMF species (G. geosporum) that most promoted its own growth. As a consequence, the altered AMF community enhanced the competitiveness of invasive S. canadensis at the expense of K. striata. Our results demonstrate that the invasive S. canadensis alters soil AMF community composition because of fungal-host preference. This change in the composition of the AMF community generates positive feedback to the invasive S. canadensis itself and decreases AM associations with native K. striata, thereby making the native K. striata less dominant.
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Kuwaiti dolocrete: petrology, geochemistry and groundwater origin
NASA Astrophysics Data System (ADS)
El-Sayed, M. I.; Fairchild, I. J.; Spiro, B.
1991-09-01
Near-surface sediments in southern Kuwait show extensive development of duricrusts. The host materials are siliciclastic sandstones of the post-Eocene Kuwait Group. Inland, the duricrusts are dominantly pedogenic calcrete (with some silcrete and gypcrete), whereas within 10-20 km of the coast, dolomite is the dominant duricrust mineral. Both these dolocretes and the inland calcretes display a similar maturation sequence in which carbonate-rich nodules develop and coalesce, carbonate progressively replacing and displacing detrital grains. The dolomite of the dolocretes forms mosaics of crystals typically 10-70 μm in size, varying from simple rhombs to spherulites. An intermediate morphology, named artichoke dolomite from its appearance in SEM, is particularly abundant. Authigenic palygorskite is associated with the dolomite. Dissolution of cores or zones within dolomite crystals has occurred. Calcite is present as sparry crystals (always post-dating dolomite) and is the expected precipitate from present-day soil and groundwaters. Chemical analyses of dolomite show highly negative values of δ13C (- to - 10.7‰ PDB) and δ18O varying from + 0.6 to + 3.3‰ PDB. The oxygen isotope values are interpreted as reflecting evaporation of a marine-based fluid. Manganese values of around 1000 ppm show that this fluid was reducing. Strontium data show variability reflecting mineral-fluid reactions. The general absence of metastable carbonates and presence of zoning in dolomite crystals suggests that meteoric dilution of seawater also occurred. Given that the duricrusts lack biogenic features, the light carbon isotope values are taken to indicate oxidation of seeping hydrocarbons. The dolocretes are interpreted as groundwater precipitates near the water table of a brackish water body formed at a time of higher relative sea level than today.
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Effects of Io's volcanos on the plasma torus and Jupiter's magnetosphere
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cheng, A.F.
1980-12-01
Io's volcanism can have dominant effects on Jupiter's magnetosphere. A model is developed in which a neutral gas torus is formed at Io's orbit by volcanic SO/sub 2/ escaping from Io. Ionization and dissociation of volcanic SO/sub 2/ is shown to be the dominant source of plasma in Jupiter's magnetosphere. The failure of Voyager observations to confirm predictions of the magnetic anomaly model is naturally explained. A 30--50 KeV sulfur and oxygen ion plasma is formed in the outer magnetosphere, with density roughly equal to the proton density there, by ionization of sulfur and oxygen atoms on highly eccentric ellipticalmore » orbits around Jupiter. When these atoms are ionized in the outer magnetosphere, they are swept up by the Jovian magnetic field and achieve 30--50 keV energies. Such atoms are created by dissociative attachment of SO/sub 2/ by < or approx. =10 eV electrons. Substantial losses of radiation-belt charged particles result from passage through the neutral gas torus. Such losses can account for observed anomalies in charged particle depletions near Io; these could not be understood in terms of satellite sweeping alone. Substantial ionization energy loss occurs for < or approx. =1 MeV protons and < or approx. =100 keV electrons; losses of < or approx. =1 MeV protons are much greater than for comparable energy electrons. Losses of < or approx. =1 MeV per nucleon ions are also severe. Other consequences of the model include intrinsic time variability in the Jovian magnetosphere, on times > or approx. =10/sup 6/ s, caused by variations in Io's volcanic activity. Charged particle losses in the neutral gas torus tend to yield dumbbell-shaped pitch-angle distributions. Negative ions are predicted in the Io plasma torus.« less
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Goji, Katsumi; Ozaki, Kayo; Sadewa, Ahmad H; Nishio, Hisahide; Matsuo, Masafumi
2006-02-01
Familial hypophosphatemic rickets is usually transmitted as an X-linked dominant disorder (XLH), although autosomal dominant forms have also been observed. Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively. The objective of the study was to describe the molecular genetic findings in a family affected by hypophosphatemic rickets with presumed autosomal dominant inheritance. We studied a family in which the father and the elder of his two daughters, but not the second daughter, were affected by hypophosphatemic rickets. The pedigree interpretation of the family suggested that genetic transmission of the disorder occurred as an autosomal dominant trait. Direct nucleotide sequencing of FGF23 and PHEX revealed that the elder daughter was heterozygous for an R567X mutation in PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an X-linked dominant trait. Unexpectedly, the father was heterozygous for this mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the father using DNA from single hair roots revealed that he was a somatic mosaic for the mutation. Haplotype analysis confirmed that the father transmitted the genotypes for 18 markers on the X chromosome equally to his two daughters. The fact that the father transmitted the mutation to only one of his two daughters indicated that he was a germline mosaic for the mutation. Somatic and germline mosaicism for an X-linked dominant mutation in PHEX may mimic autosomal dominant inheritance.
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Cerebral dominance for speech and handwriting of patients with cortical vascular malformations.
Sass, K J; Buchanan, C P; Westerveld, M; Spencer, D D
1994-10-01
Lateralization of speech dominance was established using amobarbital for 22 patients with vascular malformations lateralized to the left cerebral hemisphere. Patients' histories were negative for clinically evident neurological events (e.g., seizures or hemorrhage) prior to adulthood. The vascular lesions were categorized as high flow arteriovenous malformations (AVMs) (n = 4), low flow AVMs (n = 6), cavernous hemangiomas (n = 10), or venous angiomas (n = 2) by reviewing angiographic findings and surgical pathology for those patients whose lesions were excised. Three of the malformations encroached upon primary language areas. The frequency of right hemisphere speech dominance was not significantly elevated in comparison with the normal population, even though the incidence of nonright-handedness was. Ninety-five percent of the patients were left hemisphere dominant for speech: only one patient, with a parietal lobe cavernous hemangioma, was found to be right hemisphere dominant for speech. This malformation did not involve the primary language areas. These findings suggest that vascular malformations do not affect speech dominance as readily as other neurological diseases, but frequently affect manual dominance.
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Li, J. C.; Diamond, P. H.
2017-03-23
Here, negative compressibility ITG turbulence in a linear plasma device (CSDX) can induce a negative viscosity increment. However, even with this negative increment, we show that the total axial viscosity remains positive definite, i.e. no intrinsic axial flow can be generated by pure ITG turbulence in a straight magnetic field. This differs from the case of electron drift wave (EDW) turbulence, where the total viscosity can turn negative, at least transiently. When the flow gradient is steepened by any drive mechanism, so that the parallel shear flow instability (PSFI) exceeds the ITG drive, the flow profile saturates at a level close to the value above which PSFI becomes dominant. This saturated flow gradient exceeds the PSFI linear threshold, and grows withmore » $$\
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NASA Astrophysics Data System (ADS)
Fu, Yu; Sun, Xiaoming; Hollings, Pete; Li, Dengfeng; Yang, Tianjian
2018-06-01
The Machangqing Cu-Mo-dominated polymetallic deposit is a porphyry-skarn-epithermal Cu-Mo (-Au) metallogenic system located in the middle part of the Jinshajiang-Ailaoshan alkaline porphyry metallogenic belt. The skarn mineralization of the Machangqing deposit mainly occurs along the contacts between the alkalic porphyry intrusions and the surrounding Lower Ordovician Xiangyang Formation rocks. We present LA-ICP-MS U-Pb ages and trace element data for titanite from the Machangqing deposit in order to investigate the origin of this deposit. Based on mineral textures and assemblages, two types of titanite are recognized in Machangqing: magmatic titanite (Type I) from the granite porphyry and hydrothermal titanite from the mineralized skarn. The coarse-grained magmatic titanite is euhedral and occurs as discrete grains in the interstices of feldspar, quartz and biotite, whereas fine- to medium-grained hydrothermal titanite crystals (Type II) are euhedral to subhedral and occur in association with skarn minerals such as garnet, pyroxene and magnetite. Magmatic titanite has lower FeO, Al2O3, F and Nb/Ta but higher TiO2, Th/U, HFSEs and Lu/Hf than hydrothermal titanite. The magmatic titanite has higher LREE/HREE ratios and total REE contents with stronger negative Eu anomalies than its mineralized skarn counterpart. Trace elemental characteristics of hydrothermal titanite in Machangqing are consistent with relatively low F contents and oxygen fugacities when compared to the neighboring Beiya gold-dominated polymetallic deposit in the same metallogenic belt. The weighted average 206Pb/238U age of 34.3 ± 1.2 Ma of hydrothermal titanite is within error but slightly younger than the age of magmatic titanite (37.5 ± 4.1 Ma), indicating that the skarn mineralization followed the emplacement of the granite porphyry and was broadly coeval with the porphyry mineralization. The porphyry and skarn types of mineralization at Machangqing were formed from the same metallogenic system. Different ore-forming conditions, such as oxygen fugacities and F contents, might be responsible for different metal enrichments at the Machangqing and Beiya deposits.
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NASA Astrophysics Data System (ADS)
Istanbulluoglu, Erkan; Bras, Rafael L.
2005-06-01
Topography acts as a template for numerous landscape processes that include hydrologic, ecologic, and biologic phenomena. These processes not only interact with each other but also contribute to shaping the landscape as they influence geomorphic processes. We have investigated the effects of vegetation on thresholds for channel initiation and landform evolution using both analytical and numerical approaches. Vegetation is assumed to form a uniform ground cover. Runoff erosion is modeled based on a power function of excess shear stress, in which shear stress efficiency is inversely proportional to vegetation cover. This approach is validated using data. Plant effect on slope stability is represented by additional cohesion provided by plant roots. Vegetation cover is assumed to reduce sediment transport rates due to physical creep processes (rainsplash, dry ravel, and expansion and contraction of sediments) according to a negative exponential relationship. Vegetation grows as a function of both available cover and unoccupied space by plants and is killed by geomorphic disturbances (runoff erosion and landsliding) and wildfires. Analytical results suggest that in an equilibrium basin with a fixed vegetation cover, plants may cause a transition in the dominant erosion process at the channel head. A runoff erosion-dominated landscape, under none or poor vegetation cover, may become landslide dominated under a denser vegetation cover. The sign of the predicted relationship between drainage density and vegetation cover depends on the relative influence of vegetation on different erosion phenomena. With model parameter values representative of the Oregon Coast Range (OCR), numerical experiments conducted using the Channel Hillslope Integrated Landscape Development (CHILD) model confirm the findings based on the analytical theory. A highly dissected fluvial landscape emerges when surface is assumed bare. When vegetation cover is modeled, landscape relief increases, resulting in hollow erosion dominated by landsliding. Interestingly, our simulations underscore the importance of vegetation disturbances by geomorphic events and wildfires on the landscape structure. Simulated landscapes resemble real-world catchments in the OCR when such disturbances are considered.
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Pareniuk, O Iu; Moshynets', O V; Tytova, L V; Levchuk, S Ie
2013-01-01
Qualitative composition of the dominating forms of microorganisms isolated from radionuclide contaminated soils has been studied. The ability to accumulate 137Cs by freshly isolated species and collection cultures that were not adapted to the presence of the radionuclide has been analyzed. It is shown that among the analyzed microorganisms the greatest ability to accumulate the radionuclide is inherent in the collection culture Bacillus megaterium UKMV-5724.
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Yang, Yongsheng; Bu, Chongfeng; Mu, Xingmin; Shao, Hongbo; Zhang, Kankan
2014-01-01
To better understand the effects of biological soil crusts (BSCs) on soil moisture and wind erosion and study the necessity and feasibility of disturbance of BSCs in the Mu Us sandland, the effects of four treatments, including moss-dominated crusts alone, Artemisia ordosica alone, bare sand, and Artemisia ordosica combined with moss-dominated crusts, on rainwater infiltration, soil moisture, and annual wind erosion were observed. The major results are as follows. (1) The development of moss-dominated crusts exacerbated soil moisture consumption and had negative effects on soil moisture in the Mu Us sandland. (2) Moss-dominated crusts significantly increased soil resistance to wind erosion, and when combined with Artemisia ordosica, this effect became more significant. The contribution of moss-dominated crusts under Artemisia ordosica was significantly lower than that of moss-dominated crusts alone in sites where vegetative coverage > 50%. (3) Finally, an appropriate disturbance of moss-dominated crusts in the rainy season in sites with high vegetative coverage improved soil water environment and vegetation succession, but disturbance in sites with little or no vegetative cover should be prohibited to avoid the exacerbation of wind erosion. PMID:24982973
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Yang, Yongsheng; Bu, Chongfeng; Mu, Xingmin; Shao, Hongbo; Zhang, Kankan
2014-01-01
To better understand the effects of biological soil crusts (BSCs) on soil moisture and wind erosion and study the necessity and feasibility of disturbance of BSCs in the Mu Us sandland, the effects of four treatments, including moss-dominated crusts alone, Artemisia ordosica alone, bare sand, and Artemisia ordosica combined with moss-dominated crusts, on rainwater infiltration, soil moisture, and annual wind erosion were observed. The major results are as follows. (1) The development of moss-dominated crusts exacerbated soil moisture consumption and had negative effects on soil moisture in the Mu Us sandland. (2) Moss-dominated crusts significantly increased soil resistance to wind erosion, and when combined with Artemisia ordosica, this effect became more significant. The contribution of moss-dominated crusts under Artemisia ordosica was significantly lower than that of moss-dominated crusts alone in sites where vegetative coverage > 50%. (3) Finally, an appropriate disturbance of moss-dominated crusts in the rainy season in sites with high vegetative coverage improved soil water environment and vegetation succession, but disturbance in sites with little or no vegetative cover should be prohibited to avoid the exacerbation of wind erosion.
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Abolhasani, Mohammad Mahdi; Naebe, Minoo; Jalali-Arani, Azam; Guo, Qipeng
2014-01-01
In this paper, intercalation of nanoclay in the miscible polymer blend of poly(vinylidene fluoride) (PVDF) and acrylic rubber(ACM) was studied. X-ray diffraction was used to investigate the formation of nanoscale polymer blend/clay hybrid. Infrared spectroscopy and X-ray analysis revealed the coexistence of β and γ crystalline forms in PVDF/Clay nanocomposite while α crystalline form was found to be dominant in PVDF/ACM/Clay miscible hybrids. Flory-Huggins interaction parameter (B) was used to further explain the miscibility phenomenon observed. The B parameter was determined by combining the melting point depression and the binary interaction model. The estimated B values for the ternary PVDF/ACM/Clay and PVDF/ACM pairs were all negative, showing both proper intercalation of the polymer melt into the nanoclay galleries and the good miscibility of PVDF and ACM blend. The B value for the PVDF/ACM blend was almost the same as that measured for the PVDF/ACM/Clay hybrid, suggesting that PVDF chains in nanocomposite hybrids interact with ACM chains and that nanoclay in hybrid systems is wrapped by ACM molecules. PMID:24551141
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Gehlot, Hukam Singh; Ardley, Julie; Tak, Nisha; ...
2016-06-23
Ensifer sp. PC2 is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from a nitrogen-fixing nodule of the tree legume P. cineraria (L.) Druce (Khejri), which is a keystone species that grows in arid and semi-arid regions of the Indian Thar desert. Strain PC2 exists as a dominant saprophyte in alkaline soils of Western Rajasthan. It is fast growing, well-adapted to arid conditions and is able to form an effective symbiosis with several annual crop legumes as well as species of mimosoid trees and shrubs. Here we describe the features of Ensifer sp. PC2, together with genome sequence informationmore » and its annotation. The 8,458,965 bp high-quality permanent draft genome is arranged into 171 scaffolds of 171 contigs containing 8,344 protein-coding genes and 139 RNA-only encoding genes, and is one of the rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project proposal.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gehlot, Hukam Singh; Ardley, Julie; Tak, Nisha
Ensifer sp. PC2 is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from a nitrogen-fixing nodule of the tree legume P. cineraria (L.) Druce (Khejri), which is a keystone species that grows in arid and semi-arid regions of the Indian Thar desert. Strain PC2 exists as a dominant saprophyte in alkaline soils of Western Rajasthan. It is fast growing, well-adapted to arid conditions and is able to form an effective symbiosis with several annual crop legumes as well as species of mimosoid trees and shrubs. Here we describe the features of Ensifer sp. PC2, together with genome sequence informationmore » and its annotation. The 8,458,965 bp high-quality permanent draft genome is arranged into 171 scaffolds of 171 contigs containing 8,344 protein-coding genes and 139 RNA-only encoding genes, and is one of the rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project proposal.« less
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Role of the Lipid Environment in the Dimerization of Transmembrane Domains of Glycophorin A
Kuznetsov, A. S.; Volynsky, P. E.; Efremov, R. G.
2015-01-01
An efficient computational approach is developed to quantify the free energy of a spontaneous association of the α-helices of proteins in the membrane environment. The approach is based on the numerical decomposition of the free energy profiles of the transmembrane (TM) helices into components corresponding to protein-protein, protein-lipid, and protein-water interactions. The method was tested for the TM segments of human glycophorin A (GpA) and two mutant forms, Gly83Ala and Thr87Val. It was shown that lipids make a significant negative contribution to the free energy of dimerization, while amino acid residues forming the interface of the helix-helix contact may be unfavorable in terms of free energy. The detailed balance between different energy contributions is highly dependent on the amino acid sequence of the TM protein segment. The results show the dominant role of the environment in the interaction of membrane proteins that is changing our notion of the driving force behind the spontaneous association of TM α-helices. Adequate estimation of the contribution of the water-lipid environment thus becomes an extremely urgent task for a rational design of new molecules targeting bitopic membrane proteins, including receptor tyrosine kinases. PMID:26798499
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Corruption: Taking into account the psychological mimicry of officials
NASA Astrophysics Data System (ADS)
Kolesin, Igor; Malafeyev, Oleg; Andreeva, Mariia; Ivanukovich, Georgiy
2017-07-01
A mathematical model of corruption with regard to psychological mimicry in the administrative apparatus with three forms of corruption is constructed. It is assumed that the change of officials forms of corruption is due to situational factors, and anti-corruption laws imply the change of the dominant form. Form's changing is modeled by the system of four differential equations (including groups of corrupt officials), describing the number of groups. The speed of the transition from group to group is expressed through the frequency of meetings. The controlling influence is expressed through the force of anticorruption laws. Two cases are discussed: strictly constant and variable (depending on the scope of one or another form). The equilibrium states that allow to specify the dominant form and investigate its stability, depending on the parameters of the psychological mimicry and rigor of anti-corruption laws are found and discussed.
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Yang, Ying; Li, Wenqi; Sheldon, Kennon M; Kou, Yu
2018-01-10
This study aims to investigate the relationship between social dominance orientation (SDO) and subjective well-being among Chinese adolescents (N = 4246), and to examine the mediating role of prosocial behaviour in this relationship. The structural equation model's results showed that SDO was negatively associated with prosocial behaviour and subjective well-being, that prosocial behaviour was positively associated with subjective well-being, and also that (low) prosocial behaviour partially mediated the negative relationship between SDO and subjective well-being. Multi-group analyses showed that the mediation model was generally similar between boys and girls, but that the negative relationship between SDO and prosocial behaviour was somewhat stronger among girls than boys. This study sheds light on how SDO is associated with positive outcomes among Chinese adolescents and highlights the mediating role of prosocial behaviour as an underlying mechanism between SDO and subjective well-being. Future studies are needed to further discover the role of culture values in the association between SDO and subjective well-being. © 2018 International Union of Psychological Science.
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Dissociation of dicyclohexyl phthalate molecule induced by low-energy electron impact
NASA Astrophysics Data System (ADS)
Lacko, Michal; Papp, Peter; Matejčík, Štefan
2018-06-01
Experimental investigation of electron ionization (EI) of and electron attachment (EA) onto dicyclohexyl phthalate (DCHP) was carried out using a crossed electron and molecular beam technique. Formation of positive and negative ions by EI and EA with the corresponding dissociation processes was studied and discussed. Due to a low ion yield of the parent positive ion, we were not able to estimate the ionization energy of DCHP. However, we estimated the appearance energies for the protonated phthalate anhydride (m/z 149) to be 10.5 eV and other significant ionic fragments of m/z 249 [DCHP—(R—2H)]+, m/z 167 [DCHP—(2R—3H)]+, and m/z 83 [C6H11]+. The reaction mechanisms of the dissociative ionization process were discussed. In the case of negative ions, we estimated the relative cross sections for a transient negative ion (TNI) and for several detected ions. At low electron energies (close to 0 eV), the TNI of DCHP molecules was the dominant ion, with products of dissociative EA dominating in broad resonances at 7.5 and 8.5 eV.
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Factors affecting the reproductive success of dominant male meerkats.
Spong, Göran F; Hodge, Sarah J; Young, Andrew J; Clutton-Brock, Tim H
2008-05-01
Identifying traits that affect the reproductive success of individuals is fundamental for our understanding of evolutionary processes. In cooperative breeders, a dominant male typically restricts mating access to the dominant female for extended periods, resulting in pronounced variation in reproductive success among males. This may result in strong selection for traits that increase the likelihood of dominance acquisition, dominance retention and reproductive rates while dominant. However, despite considerable research on reproductive skew, few studies have explored the factors that influence these three processes among males in cooperative species. Here we use genetic, behavioural and demographic data to investigate the factors affecting reproductive success in dominant male meerkats (Suricata suricatta). Our data show that dominant males sire the majority of all offspring surviving to 1 year. A male's likelihood of becoming dominant is strongly influenced by age, but not by weight. Tenure length and reproductive rate, both important components of dominant male reproductive success, are largely affected by group size and composition, rather than individual traits. Dominant males in large groups have longer tenures, but after this effect is controlled, male tenure length also correlates negatively to the number of adult females in the group. Male reproductive rate also declines as the number of intra- and extra-group competitors increases. As the time spent in the dominant position and reproductive rate while dominant explain > 80% of the total variance in reproductive success, group composition thus has major implications for male reproductive success.
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Segerson, Nathan M; Wasmund, Stephen L; Abedin, Moeen; Pai, Rakesh K; Daccarett, Marcos; Akoum, Nazem; Wall, T Scott; Klein, Richard C; Freedman, Roger A; Hamdan, Mohamed H
2007-03-01
Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = -0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease.
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Riley, Stephen C.; Tatara, Christopher P.; Berejikian, Barry A.; Flagg, Thomas A.
2009-01-01
We quantified the aggression, feeding, dominance, position choice, and territory size of naturally reared steelhead Oncorhynchus mykiss fry stocked with two types of hatchery-reared fry (from conventional and enriched rearing environments) at two densities in experimental flumes to determine how rearing environment and fish density affect the behavior of steelhead fry. We found that fry density had a significant effect on most response variables but that rearing treatment did not. The rates of threats and attacks were positively correlated with fry density, but the overall feeding rate was negatively correlated. Naturally reared fry were dominant more often at low densities, and hatchery-reared fry were dominant more often at high densities. There were no significant effects of hatchery rearing treatment on aggression, feeding, dominance, or territory size. The only significant effect of rearing treatment was on the position of naturally reared fry, which occupied more upstream positions when stocked with conventional than with enriched hatchery-reared fry. Overall, rearing environment had relatively little influence on the behavior of steelhead fry. Our results indicate that stocking hatchery-reared steelhead fry at low densities may have effects on similar-size wild fish comparable to an equivalent increase in the density of wild fish. We suggest that releasing hatchery-reared steelhead fry as a supplementation strategy may have few direct negative ecological effects on wild fry.
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Sato, Atsuko; Sasaki, Shu; Matsuzaki, Jun; Yamamoto, Kotaro T
2014-09-01
Gravitropism and phototropism of the primary inflorescence stems were examined in a dominant Aux/IAA mutant of Arabidopsis, axr2/iaa7, which did not display either tropism in hypocotyls. axr2-1 stems completely lacked gravitropism in the dark but slowly regained it in light condition. Though wild-type stems showed positive phototropism, axr2 stems displayed negative phototropism with essentially the same light fluence-response curve as the wild type (WT). Application of 1-naphthaleneacetic acid-containing lanolin to the stem tips enhanced the positive phototropism of WT, and reduced the negative phototropism of axr2. Decapitation of stems caused a small negative phototropism in WT, but did not affect the negative phototropism of axr2. p-glycoprotein 1 (pgp1) pgp19 double mutants showed no phototropism, while decapitated double mutants exhibited negative phototropism. Expression of auxin-responsive IAA14/SLR, IAA19/MSG2 and SAUR50 genes was reduced in axr2 and pgp1 pgp19 stems relative to that of WT. These suggest that the phototropic response of stem is proportional to the auxin supply from the shoot apex, and that negative phototropism may be a basal response to unilateral blue-light irradiation when the levels of auxin or auxin signaling are reduced to the minimal level in the primary stems. In contrast, all of these treatments reduced or did not affect gravitropism in wild-type or axr2 stems. Tropic responses of the transgenic lines that expressed axr2-1 protein by the endodermis-specific promoter suggest that AXR2-dependent auxin response in the endodermis plays a more crucial role in gravitropism than in phototropism in stems but no significant roles in either tropism in hypocotyls.
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2009-11-01
and audience presence interact to affect aggressive behaviour in response to self-relevant negative feedback. It was hypothesized that aggression...Audience Presence Impression management theory posits that a key motivation behind human behaviour is to develop a favourable impression of oneself...discrepancy between a negative self-view and need for dominance results in defensive behaviours designed to validate their own favourable self-view
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Heterotrophic bacterial flora in aquaculture area around Xuejiadao
NASA Astrophysics Data System (ADS)
Du, Zongjun; Li, Yun; Yu, Dehua; Wang, Xianghong; Chen, Jixiang; Robertson, P. A. W.; Austin, B.; Xu, Huaishu
2002-10-01
From Oct., 1999 to Oct., 2000, the heterotrophic bacterial flora in the aquaculture area around Xuejiadao was investigated. The result shows that the populations of the heterotrophic bacteria are heavier in summer and autumn than those in winter and spring. The average populations in seawater, sediment, the surface of seaweed and the surface of fish are 1.4×104cfu mL-1, 5.4×106cfu g-1, 1.5×106cfu g-1 and 1.8×103cfu cm-2, respectively. A total of 301 strains were isolated, among them 259 were Gram-negative. All the Gram-negative bacteria belong to 13 genera and some genera of Enterobacteriaceae. The communities of bacteria are slightly different among the samples. In the body surface of fish, Genus vibrio is dominant. In the remaining samples, dominant genus is Aeromonas.
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Within-Subject Correlation Analysis to Detect Functional Areas Associated With Response Inhibition.
Yamasaki, Tomoko; Ogawa, Akitoshi; Osada, Takahiro; Jimura, Koji; Konishi, Seiki
2018-01-01
Functional areas in fMRI studies are often detected by brain-behavior correlation, calculating across-subject correlation between the behavioral index and the brain activity related to a function of interest. Within-subject correlation analysis is also employed in a single subject level, which utilizes cognitive fluctuations in a shorter time period by correlating the behavioral index with the brain activity across trials. In the present study, the within-subject analysis was applied to the stop-signal task, a standard task to probe response inhibition, where efficiency of response inhibition can be evaluated by the stop-signal reaction time (SSRT). Since the SSRT is estimated, by definition, not in a trial basis but from pooled trials, the correlation across runs was calculated between the SSRT and the brain activity related to response inhibition. The within-subject correlation revealed negative correlations in the anterior cingulate cortex and the cerebellum. Moreover, the dissociation pattern was observed in the within-subject analysis when earlier vs. later parts of the runs were analyzed: negative correlation was dominant in earlier runs, whereas positive correlation was dominant in later runs. Regions of interest analyses revealed that the negative correlation in the anterior cingulate cortex, but not in the cerebellum, was dominant in earlier runs, suggesting multiple mechanisms associated with inhibitory processes that fluctuate on a run-by-run basis. These results indicate that the within-subject analysis compliments the across-subject analysis by highlighting different aspects of cognitive/affective processes related to response inhibition.
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van der Lee, Arie; Roche, Gilles H; Wantz, Guillaume; Moreau, Joël J E; Dautel, Olivier J; Filhol, Jean-Sébastien
2018-04-28
Thermal expansion coefficients of most materials are usually small, typically up to 50 parts per million per kelvin, and positive, i.e. materials expand when heated. Some materials show an atypical shrinking behavior in one or more crystallographic directions when heated. Here we show that a high mobility thiophene-based organic semiconductor, BHH-BTBT , has an exceptionally large negative expansion between 95 and 295 K (-216 < α 2 = α b < -333 MK -1 ), being compensated by an even larger positive expansion in the perpendicular direction (287 < α 1 < 634 MK -1 ). It is shown that these anomalous expansivities are completely absent in C8-BTBT , a much studied organic semiconductor with a closely related molecular formula and 3D crystallographic structure. Complete theoretical characterization of BHH-BTBT using ab initio molecular dynamics shows that below ∼200 K two different α and β domains exist of which one is dominant but which dynamically exchange around and above 210 K. A supercritical-like transition from an α dominated phase to a β dominated phase is observed using DSC measurements, UV-VIS spectroscopy, and X-ray diffraction. The origin of the extreme negative and positive thermal expansion is related to steric hindrance between adjacent tilted thiophene units and strongly enhanced by attractive S···S and S···C interactions within the highly anharmonic mixed-domain phase. This material could trigger the tailoring of optoelectronic devices highly sensitive to strain and temperature.
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NASA Astrophysics Data System (ADS)
Huang, Jie; Xu, Fanghua; Zhou, Kuanbo; Xiu, Peng; Lin, Yanluan
2017-08-01
Temporal evolution of near-surface chlorophyll (CHL) associated with mesoscale eddies over entire eddy lifespan is complicated. Based on satellite measurements and a reanalysis data set, we identify and quantify major temporal and spatial CHL responses in cyclonic eddies in the southeastern Pacific, and explore the associated mechanisms. Only few temporal CHL variations can be directly linked to the four primary mechanisms: "eddy pumping," "eddy trapping," "eddy stirring," and "eddy-induced Ekman pumping." About 80% of the temporal CHL variations are too complex to be explained by a single mechanism. Five characteristic CHL responses, including classic dipoles (CD), positive-dominant dipoles (PD), negative-dominant dipoles (ND), positive monopoles (PM), and negative monopoles (NM) are identified using the self-organizing map (SOM). CD, a dominant response induced primarily by "eddy stirring," has a continued increasing of frequency of occurrence with time, although its contribution to the total CHL variability remains low. As the secondary prominent response, NM has two peaks of frequency of occurrence at eddy formation and maturation stages, mainly accounted by "eddy trapping" after eddy breakup and "eddy-induced Ekman pumping," respectively. The sum of frequency of occurrence of PD and PM are comparable to that of NM. The initial positive CHL at eddy formation stage is associated with "eddy trapping." The significant positive CHL increase from the eddy intensification to early decay stage is mainly attributed to "eddy pumping." Although the frequency of occurrence of ND is the smallest, its contribution to negative CHL anomalies is unnegligible.
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Iwata, Yuko; Katanosaka, Yuki; Arai, Yuji; Shigekawa, Munekazu; Wakabayashi, Shigeo
2009-03-01
Muscular dystrophy is a severe degenerative disorder of skeletal muscle characterized by progressive muscle weakness. One subgroup of this disease is caused by a defect in the gene encoding one of the components of the dystrophin-glycoprotein complex, resulting in a significant disruption of membrane integrity and/or stability and, consequently, a sustained increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)). In the present study, we demonstrate that muscular dystrophy is ameliorated in two animal models, dystrophin-deficient mdx mice and delta-sarcoglycan-deficient BIO14.6 hamsters by dominant-negative inhibition of the transient receptor potential cation channel, TRPV2, a principal candidate for Ca(2+)-entry pathways. When transgenic (Tg) mice expressing a TRPV2 mutant in muscle were crossed with mdx mice, the [Ca(2+)](i) increase in muscle fibers was reduced by dominant-negative inhibition of endogenous TRPV2. Furthermore, histological, biochemical and physiological indices characterizing dystrophic pathology, such as an increased number of central nuclei and fiber size variability/fibrosis/apoptosis, elevated serum creatine kinase levels, and reduced muscle performance, were all ameliorated in the mdx/Tg mice. Similar beneficial effects were also observed in the muscles of BIO14.6 hamsters infected with adenovirus carrying mutant TRPV2. We propose that TRPV2 is a principal Ca(2+)-entry route leading to a sustained [Ca(2+)](i) increase and muscle degeneration, and that it is a promising therapeutic target for the treatment of muscular dystrophy.
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Abnormal proactive and reactive cognitive control during conflict processing in major depression.
Vanderhasselt, Marie-Anne; De Raedt, Rudi; De Paepe, Annick; Aarts, Kristien; Otte, Georges; Van Dorpe, Jan; Pourtois, Gilles
2014-02-01
According to the Dual Mechanisms of Control framework, cognitive control consists of two complementary components: proactive control refers to anticipatory maintenance of goal-relevant information, whereas reactive control acts as a correction mechanism that is activated when a conflict occurs. Possibly, the well-known diminished inhibitory control in response to negative stimuli in Major Depressive Disorder (MDD) patients stems from a breakdown in proactive control, and/or anomalies in reactive cognitive control. In our study, MDD patients specifically showed increased response latencies when actively inhibiting a dominant response to a sad compared with a happy face. This condition was associated with a longer duration of a dominant ERP topography (800-900 ms poststimulus onset) and a stronger activity in the bilateral dorsal anterior cingulate cortex, reflecting abnormal reactive control when inhibiting attention to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive cognitive control when preparing for the upcoming imperative stimulus (abnormal modulation of the contingent negative variation component), accompanied by more activity in brain regions belonging to the default mode network. All together, deficits to inhibit attention to negative information in MDD might originate from an abnormal use of both proactive resources and reactive control processes. PsycINFO Database Record (c) 2014 APA, all rights reserved.
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Diaz, Arturo; Gallei, Andreas
2012-01-01
All positive-strand RNA viruses replicate their genomes in association with rearranged intracellular membranes such as single- or double-membrane vesicles. Brome mosaic virus (BMV) RNA synthesis occurs in vesicular endoplasmic reticulum (ER) membrane invaginations, each induced by many copies of viral replication protein 1a, which has N-terminal RNA capping and C-terminal helicase domains. Although the capping domain is responsible for 1a membrane association and ER targeting, neither this domain nor the helicase domain was sufficient to induce replication vesicle formation. Moreover, despite their potential for mutual interaction, the capping and helicase domains showed no complementation when coexpressed in trans. Cross-linking showed that the capping and helicase domains each form trimers and larger multimers in vivo, and the capping domain formed extended, stacked, hexagonal lattices in vivo. Furthermore, coexpressing the capping domain blocked the ability of full-length 1a to form replication vesicles and replicate RNA and recruited full-length 1a into mixed hexagonal lattices with the capping domain. Thus, BMV replication vesicle formation and RNA replication depend on the direct linkage and concerted action of 1a's self-interacting capping and helicase domains. In particular, the capping domain's strong dominant-negative effects showed that the ability of full-length 1a to form replication vesicles was highly sensitive to disruption by non-productively titrating lattice-forming self-interactions of the capping domain. These and other findings shed light on the roles and interactions of 1a domains in replication compartment formation and support prior results suggesting that 1a induces replication vesicles by forming a capsid-like interior shell. PMID:22090102
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NASA Astrophysics Data System (ADS)
Krider, E. P.; Baffou, G.; Murray, N. D.; Willett, J. C.
2004-12-01
We have analyzed the shapes and other characteristics of the electric field, E, and dE/dt waveforms that were radiated by leader steps just before the first return stroke in cloud-to-ocean lightning. dE/dt waveforms were recorded using an 8-bit digitizer sampling at 100 MHz, and an integrated waveform, Eint, was computed by numerically integrating dE/dt and comparing the result with an analog E waveform digitized at 10 MHz. All signals were recorded under conditions where the lightning locations were known and there was minimal distortion in the fields due to the effects of ground-wave propagation. The dE/dt waveforms radiated by leader steps tend to fall into three categories: (1) "simple" - an isolated negative peak that is immediately followed by a positive overshoot (where negative polarity follows the normal physics convention), (2) "double" - two simple waveforms that occur at almost the same time, and (3) "burst" - a complex cluster of pulses with a total duration of about one microsecond. In this paper, we will give examples of each of these waveform types, and we will summarize their characteristics on a submicrosecond time-scale. For example, in an interval starting 9 μ s before to 4 μ s before the largest, negative (dominant) peak in dE/dt peak in the return stroke, 131 first strokes produced a total of 296 impulses with a peak amplitude greater than 10% of the dominant peak, and the average amplitude of these pulses was 0.21 of the dominant peak. The last leader step in a 12 μ s interval before the dominant peak was a simple waveform in 51 first strokes, and in these cases, the average time-interval between the peak dE/dt of the step and the dominant peak of the stroke was 5.8 ± 1.7 μ s, a value that is in good agreement with prior measurements. The median full-width-at-half-maximum (FWHM) of 274 simple Eint signatures was 141 ns, and the associated mean and standard deviation were 187 ± 131 ns.
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Dominance-diversity relationships in ant communities differ with invasion.
Arnan, Xavier; Andersen, Alan N; Gibb, Heloise; Parr, Catherine L; Sanders, Nathan J; Dunn, Robert R; Angulo, Elena; Baccaro, Fabricio B; Bishop, Tom R; Boulay, Raphaël; Castracani, Cristina; Cerdá, Xim; Toro, Israel Del; Delsinne, Thibaut; Donoso, David A; Elten, Emilie K; Fayle, Tom M; Fitzpatrick, Matthew C; Gómez, Crisanto; Grasso, Donato A; Grossman, Blair F; Guénard, Benoit; Gunawardene, Nihara; Heterick, Brian; Hoffmann, Benjamin D; Janda, Milan; Jenkins, Clinton N; Klimes, Petr; Lach, Lori; Laeger, Thomas; Leponce, Maurice; Lucky, Andrea; Majer, Jonathan; Menke, Sean; Mezger, Dirk; Mori, Alessandra; Moses, Jimmy; Munyai, Thinandavha Caswell; Paknia, Omid; Pfeiffer, Martin; Philpott, Stacy M; Souza, Jorge L P; Tista, Melanie; Vasconcelos, Heraldo L; Retana, Javier
2018-05-30
The relationship between levels of dominance and species richness is highly contentious, especially in ant communities. The dominance-impoverishment rule states that high levels of dominance only occur in species-poor communities, but there appear to be many cases of high levels of dominance in highly diverse communities. The extent to which dominant species limit local richness through competitive exclusion remains unclear, but such exclusion appears more apparent for non-native rather than native dominant species. Here we perform the first global analysis of the relationship between behavioral dominance and species richness. We used data from 1,293 local assemblages of ground-dwelling ants distributed across five continents to document the generality of the dominance-impoverishment rule, and to identify the biotic and abiotic conditions under which it does and does not apply. We found that the behavioral dominance-diversity relationship varies greatly, and depends on whether dominant species are native or non-native, whether dominance is considered as occurrence or relative abundance, and on variation in mean annual temperature. There were declines in diversity with increasing dominance in invaded communities, but diversity increased with increasing dominance in native communities. These patterns occur along the global temperature gradient. However, positive and negative relationships are strongest in the hottest sites. We also found that climate regulates the degree of behavioral dominance, but differently from how it shapes species richness. Our findings imply that, despite strong competitive interactions among ants, competitive exclusion is not a major driver of local richness in native ant communities. Although the dominance-impoverishment rule applies to invaded communities, we propose an alternative dominance-diversification rule for native communities. © 2018 John Wiley & Sons Ltd.
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The end of a monolith: Deconstructing the Cnn-Polo interaction.
Eisman, Robert C; Phelps, Melissa A S; Kaufman, Thomas C
2016-04-02
In Drosophila melanogaster a functional pericentriolar matrix (PCM) at mitotic centrosomes requires Centrosomin-Long Form (Cnn-LF) proteins. Moreover, tissue culture cells have shown that the centrosomal localization of both Cnn-LF and Polo kinase are co-dependent, suggesting a direct interaction. Our recent study found Cnn potentially binds to and is phosphorylated by Polo kinase at 2 residues encoded by Exon1A, the initiating exon of a subset of Cnn isoforms. These interactions are required for the centrosomal localization of Cnn-LF in syncytial embryos and a mutation of either phosphorylation site is sufficient to block localization of both mutant and wild-type Cnn when they are co-expressed. Immunoprecipitation experiments show that Cnn-LF interacts directly with mitotically activated Polo kinase and requires the 2 phosphorylation sites in Exon1A. These IP experiments also show that Cnn-LF proteins form multimers. Depending on the stoichiometry between functional and mutant peptides, heteromultimers exhibit dominant negative or positive trans-complementation (rescue) effects on mitosis. Additionally, following the completion of meiosis, Cnn-Short Form (Cnn-SF) proteins are required for polar body formation in embryos, a process previously shown to require Polo kinase. These findings, when combined with previous work, clearly demonstrate the complexity of cnn and show that a view of cnn as encoding a single peptide is too simplistic.
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The end of a monolith: Deconstructing the Cnn-Polo interaction
2016-01-01
ABSTRACT In Drosophila melanogaster a functional pericentriolar matrix (PCM) at mitotic centrosomes requires Centrosomin-Long Form (Cnn-LF) proteins. Moreover, tissue culture cells have shown that the centrosomal localization of both Cnn-LF and Polo kinase are co-dependent, suggesting a direct interaction. Our recent study found Cnn potentially binds to and is phosphorylated by Polo kinase at 2 residues encoded by Exon1A, the initiating exon of a subset of Cnn isoforms. These interactions are required for the centrosomal localization of Cnn-LF in syncytial embryos and a mutation of either phosphorylation site is sufficient to block localization of both mutant and wild-type Cnn when they are co-expressed. Immunoprecipitation experiments show that Cnn-LF interacts directly with mitotically activated Polo kinase and requires the 2 phosphorylation sites in Exon1A. These IP experiments also show that Cnn-LF proteins form multimers. Depending on the stoichiometry between functional and mutant peptides, heteromultimers exhibit dominant negative or positive trans-complementation (rescue) effects on mitosis. Additionally, following the completion of meiosis, Cnn-Short Form (Cnn-SF) proteins are required for polar body formation in embryos, a process previously shown to require Polo kinase. These findings, when combined with previous work, clearly demonstrate the complexity of cnn and show that a view of cnn as encoding a single peptide is too simplistic. PMID:27096551
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Illegitimate WNT signaling promotes proliferation of multiple myeloma cells
Derksen, Patrick W. B.; Tjin, Esther; Meijer, Helen P.; Klok, Melanie D.; Mac Gillavry, Harold D.; van Oers, Marinus H. J.; Lokhorst, Henk M.; Bloem, Andries C.; Clevers, Hans; Nusse, Roel; van der Neut, Ronald; Spaargaren, Marcel; Pals, Steven T.
2004-01-01
The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes. Given their oncogenic potential, WNT signals form a class of paracrine growth factors that could act to influence MM cell growth. In this paper, we report that MM cells have hallmarks of active WNT signaling, whereas the cells have not undergone detectable mutations in WNT signaling genes such as adenomatous polyposis coli and β-catenin (CTNNB1). We show that the malignant MM plasma cells overexpress β-catenin, including its N-terminally unphosphorylated form, suggesting active β-catenin/T cell factor-mediated transcription. Further accumulation and nuclear localization of β-catenin, and/or increased cell proliferation, was achieved by stimulation of WNT signaling with either Wnt3a, LiCl, or the constitutively active S33Y mutant of β-catenin. In contrast, by blocking WNT signaling by dominant-negative T cell factor, we can interfere with the growth of MM cells. We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer. PMID:15067127
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The Origin of the Milky Way's Halo Age Distribution
NASA Astrophysics Data System (ADS)
Carollo, Daniela; Tissera, Patricia B.; Beers, Timothy C.; Gudin, Dmitrii; Gibson, Brad K.; Freeman, Ken C.; Monachesi, Antonela
2018-05-01
We present an analysis of the radial age gradients for the stellar halos of five Milky Way (MW) mass-sized systems simulated as part of the Aquarius Project. The halos show a diversity of age trends, reflecting their different assembly histories. Four of the simulated halos possess clear negative age gradients, ranging from approximately ‑7 to ‑19 Myr kpc‑1, shallower than those determined by recent observational studies of the Milky Way’s stellar halo. However, when restricting the analysis to the accreted component alone, all of the stellar halos exhibit a steeper negative age gradient with values ranging from ‑8 to ‑32 Myr kpc‑1, closer to those observed in the Galaxy. Two of the accretion-dominated simulated halos show a large concentration of old stars in the center, in agreement with the Ancient Chronographic Sphere reported observationally. The stellar halo that best reproduces the current observed characteristics of the age distributions of the Galaxy is that formed principally by the accretion of small satellite galaxies. Our findings suggest that the hierarchical clustering scenario can reproduce the MW’s halo age distribution if the stellar halo was assembled from accretion and the disruption of satellite galaxies with dynamical masses less than ∼109.5 M ⊙, and a minimal in situ contribution.
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Fu, Ssu-Ju; Jeng, Chung-Jiuan; Ma, Chia-Hao; Peng, Yi-Jheng; Lee, Chi-Ming; Fang, Ya-Ching; Lee, Yi-Ching; Tang, Sung-Chun; Hu, Meng-Chun; Tang, Chih-Yung
2017-03-01
Voltage-gated Ca V 2.1 channels comprise a pore-forming α 1A subunit with auxiliary α 2 δ and β subunits. Ca V 2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding the Ca V 2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of Ca V 2.1 wild-type (WT) protein expression via aberrant proteasomal degradation. Here, we set out to delineate the protein degradation mechanism of human Ca V 2.1 subunit by identifying RNF138, an E3 ubiquitin ligase, as a novel Ca V 2.1-binding partner. In neurons, RNF138 and Ca V 2.1 coexist in the same protein complex and display notable subcellular colocalization at presynaptic and postsynaptic regions. Overexpression of RNF138 promotes polyubiquitination and accelerates protein turnover of Ca V 2.1. Disrupting endogenous RNF138 function with a mutant (RNF138-H36E) or shRNA infection significantly upregulates the Ca V 2.1 protein level and enhances Ca V 2.1 protein stability. Disrupting endogenous RNF138 function also effectively rescues the defective protein expression of EA2 mutants, as well as fully reversing EA2 mutant-induced excessive proteasomal degradation of Ca V 2.1 WT subunits. RNF138-H36E coexpression only partially restores the dominant-negative effect of EA2 mutants on Ca V 2.1 WT functional expression, which can be attributed to defective membrane trafficking of Ca V 2.1 WT in the presence of EA2 mutants. We propose that RNF138 plays a critical role in the homeostatic regulation of Ca V 2.1 protein level and functional expression and that RNF138 serves as the primary E3 ubiquitin ligase promoting EA2-associated aberrant degradation of human Ca V 2.1 subunits. SIGNIFICANCE STATEMENT Loss-of-function mutations in the human Ca V 2.1 subunit are linked to episodic ataxia type 2 (EA2), a dominantly inherited disease characterized by paroxysmal attacks of ataxia and nystagmus. EA2-causing mutants may exert dominant-negative effects on the Ca V 2.1 wild-type subunit via aberrant proteasomal degradation. The molecular nature of the Ca V 2.1 ubiquitin-proteasome degradation pathway is currently unknown. The present study reports the first identification of an E3 ubiquitin ligase for Ca V 2.1, RNF138. Ca V 2.1 protein stability is dynamically regulated by RNF138 and auxiliary α 2 δ and β subunits. We provide a proof of concept that protecting the human Ca V 2.1 subunit from excessive proteasomal degradation with specific interruption of endogenous RNF138 function may partially contribute to the future development of a novel therapeutic strategy for EA2 patients. Copyright © 2017 the authors 0270-6474/17/372485-19$15.00/0.
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NASA Astrophysics Data System (ADS)
Bras, R. L.; Istanbulluoglu, E.
2004-12-01
Topography acts as a template for numerous landscape processes that includes hydrologic, ecologic and biologic phenomena. These processes not only interact with each other but also contribute to shaping the landscape as they influence geomorphic processes. We have investigated the effects of vegetation on known geomorphic relations, thresholds for channel initiation and landform evolution, using both analytical and numerical approaches. Vegetation is assumed to form a uniform ground cover. Runoff erosion is modeled based on power function of excess shear stress, in which shear stress efficiency is inversely proportional to vegetation cover. Plant effect on slope stability is represented by additional cohesion provided by plant roots. Vegetation cover is assumed to reduce sediment transport rates due to physical creep processes (rainsplash, dry ravel, and expansion and contraction of sediments) according to a negative exponential relationship. Vegetation grows as a function of both available cover and unoccupied space by plants, and is killed by geomorphic disturbances (runoff erosion and landsliding), and wildfires. Analytical results suggest that, in an equilibrium basin with a fixed vegetation cover, plants may cause a transition in the dominant erosion process at the channel head. A runoff erosion dominated landscape, under none or loose vegetation cover, may become landslide dominated under a denser vegetation cover. The sign of the predicted relationship between drainage density and vegetation cover depends on the relative influence of vegetation on different erosion phenomena. With model parameter values representative of the Oregon Coast Range (OCR), numerical experiments conducted using the CHILD model. Numerical experiments reveal the importance of vegetation disturbances on the landscape structure. Simulated landscapes resemble real-world catchments in the OCR when vegetation disturbances are considered.
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Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.
Kim, Hyo Jeong; Lv, Ping; Sihn, Choong-Ryoul; Yamoah, Ebenezer N
2011-01-14
Despite advances in identifying deafness genes, determination of the underlying cellular and functional mechanisms for auditory diseases remains a challenge. Mutations of the human K(+) channel hKv7.4 lead to post-lingual progressive hearing loss (DFNA2), which affects world-wide population with diverse racial backgrounds. Here, we have generated the spectrum of point mutations in the hKv7.4 that have been identified as diseased mutants. We report that expression of five point mutations in the pore region, namely L274H, W276S, L281S, G285C, and G296S, as well as the C-terminal mutant G321S in the heterologous expression system, yielded non-functional channels because of endoplasmic reticulum retention of the mutant channels. We mimicked the dominant diseased conditions by co-expressing the wild-type and mutant channels. As compared with expression of wild-type channel alone, the blend of wild-type and mutant channel subunits resulted in reduced currents. Moreover, the combinatorial ratios of wild type:mutant and the ensuing current magnitude could not be explained by the predictions of a tetrameric channel and a dominant negative effect of the mutant subunits. The results can be explained by the dependence of cell surface expression of the mutant on the wild-type subunit. Surprisingly, a transmembrane mutation F182L, which has been identified in a pre-lingual progressive hearing loss patient in Taiwan, yielded cell surface expression and functional features that were similar to that of the wild type, suggesting that this mutation may represent redundant polymorphism. Collectively, these findings provide traces of the cellular mechanisms for DFNA2.
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River mouth morphodynamics - Examples from small, mountainous rivers (Invited)
NASA Astrophysics Data System (ADS)
Warrick, J. A.
2013-12-01
Small, high-sediment yield rivers are known to discharge massive amounts of sediment to the world's oceans. Because of these high rates of sediment discharge, many of these small rivers provide important sources of sediment to littoral cells, such as those along the west coasts of North and South America. Sediment discharge from these small watersheds is commonly ephemeral and dominated by infrequent high flow. Thus, the morphodynamic states of these river mouths will vary with time, often being 'wave dominated' for the majority of the year and then changing to 'river dominated' during river sediment discharge events. Here I will provide a summary of recent observations of the morphodynamics of river mouths along California that reveal that sediment dispersal and deposition patterns vary owing to the sediment transport processes at the river mouths, which are influenced by the buoyancy of the river discharge. During low rates of sediment discharge and low river sediment concentrations, sediment dispersal will occur in hypopycnal (positively buoyant) plumes and sand deposition will be close to the river mouth. These conditions commonly result in transfer of sand from the river delta to the littoral cell during the first 1-2 years following the river discharge event. During high rates of sediment discharge and high river sediment concentrations, river discharge may form hyperpycnal (negatively buoyant) plumes and disperse sand to deeper portions of the continental shelf, where transfer back to the littoral cell may take decades or may not occur. High-resolution bathymetry from southern California provides several examples of sand dispersal by hyperpycnal plumes to regions of the inner and middle continental shelf. Thus, sediment dispersal from river mouths influences coastal morphodynamics, morphology, and the rates and timing of sediment supply to littoral cells.
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Wu, Bo; Zhou, Yang; Wang, Yu; Yang, Xiang-Min; Liu, Zhen-Yu; Li, Jiang-Hua; Feng, Fei; Chen, Zhi-Nan; Jiang, Jian-Li
2016-01-01
Hepatocellular carcinoma (HCC) is currently the third most common cause of cancer-related death in the Asia-Pacific region. Our previous work showed that knockdown of CD98 significantly inhibits malignant HCC cell phenotypes in vitro and in vivo. The level of CD98 in the membrane is tightly regulated to mediate complex processes associated with cell–cell communication and intracellular signaling. In addition, the intracellular domain of CD98 (CD98-ICD) seems to be of vital importance for recycling CD98 to the membrane after it is endocytosed. The intracellular and transmembrane domains of CD98 associate with β-integrins (primarily β1 but also β3), and this association is essential for CD98 mediation of integrin-like signaling and complements dominant suppression of β1-integrin. We speculated that isolated CD98-ICD would similarly suppress β1-integrin activation and inhibit the malignant behaviors of cancer cells. In particular, the exact role of CD98-ICD has not been studied independently in HCC. In this study, we found that ectopic expression of CD98-ICD inhibited the malignant phenotypes of HCC cells, and the mechanism possibly involves β1-integrin suppression. Moreover, the expression levels of CD98, β1-integrin-A (the activated form of β1-integrin) and Ki-67 were significantly increased in HCC tissues relative to those of normal liver tissues. Therefore, our preliminary study indicates that ectopic CD98-ICD has an inhibitory role in the malignant development of HCC, and shows that CD98-ICD acts as a dominant negative mutant of CD98 that attenuates β1-integrin activation. CD98-ICD may emerge as a promising candidate for antitumor treatment. PMID:27834933
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Hossain, M G; Zyroul, R; Pereira, B P; Kamarul, T
2012-01-01
Grip strength is an important measure used to monitor the progression of a condition, and to evaluate outcomes of treatment. We assessed how various physical and social factors predict normal grip strength in an adult Malaysian population of mixed Asian ethnicity (254 men, 246 women). Grip strength was recorded using the Jamar dynamometer. The mean grip strength for the dominant hand was 29.8 kg for men and 17.6 kg for women. Multiple regression analysis demonstrated that the dominant hand grip strength was positively associated with height and body mass index, and negatively associated with age for both sexes. Dominant hand grip strength was related to work status for men (p < 0.05) but not for women. However, there was no difference in grip strength among ethnic groups.
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Negative ion source with hollow cathode discharge plasma
Hershcovitch, Ady; Prelec, Krsto
1983-01-01
A negative ion source of the type where negative ions are formed by bombarding a low-work-function surface with positive ions and neutral particles from a plasma, wherein a highly ionized plasma is injected into an anode space containing the low-work-function surface. The plasma is formed by hollow cathode discharge and injected into the anode space along the magnetic field lines. Preferably, the negative ion source is of the magnetron type.
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Reactions to Racial Trespassing.
Maykovich, Minako K
1978-10-01
Three trespassers into the "body territory" of racial groups-a white woman with an Afro wig, a black with a blond wig, and a Japanese American with a blond wig-invoked reactions among 144 white, black, and Japanese American female university students. The major findings were as follows: (a) Dominant group trespassing was more likely to be viewed in cultural perspectives, while minority trespassing was viewed in a racial context; (b) Minority members tended to view minority trespassing more negatively than dominant group trespassing.
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NIPA1 Gene Mutations Cause Autosomal Dominant Hereditary Spastic Paraplegia (SPG6)
Rainier, Shirley; Chai, Jing-Hua; Tokarz, Debra; Nicholls, Robert D.; Fink, John K.
2003-01-01
The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications. PMID:14508710
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Kievit, Anneke; Tessadori, Federico; Douben, Hannie; Jordens, Ingrid; Maurice, Madelon; Hoogeboom, Jeannette; Hennekam, Raoul; Nampoothiri, Sheela; Kayserili, Hülya; Castori, Marco; Whiteford, Margo; Motter, Connie; Melver, Catherine; Cunningham, Michael; Hing, Anne; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Richieri-Costa, Antonio; Baas, Annette F; Breugem, Corstiaan C; Duran, Karen; Massink, Maarten; Derksen, Patrick W B; van IJcken, Wilfred F J; van Unen, Leontine; Santos-Simarro, Fernando; Lapunzina, Pablo; Gil-da Silva Lopes, Vera L; Lustosa-Mendes, Elaine; Krall, Max; Slavotinek, Anne; Martinez-Glez, Victor; Bakkers, Jeroen; van Gassen, Koen L I; de Klein, Annelies; van den Boogaard, Marie-José H; van Haaften, Gijs
2018-02-01
Blepharocheilodontic syndrome (BCDS) consists of lagophthalmia, ectropion of the lower eyelids, distichiasis, euryblepharon, cleft lip/palate and dental anomalies and has autosomal dominant inheritance with variable expression. We identified heterozygous variants in two genes of the cadherin-catenin complex, CDH1, encoding E-cadherin, and CTNND1, encoding p120 catenin delta1 in 15 of 17 BCDS index patients, as was recently described in a different publication. CDH1 plays an essential role in epithelial cell adherence; CTNND1 binds to CDH1 and controls the stability of the complex. Functional experiments in zebrafish and human cells showed that the CDH1 variants impair the cell adhesion function of the cadherin-catenin complex in a dominant-negative manner. Variants in CDH1 have been linked to familial hereditary diffuse gastric cancer and invasive lobular breast cancer; however, no cases of gastric or breast cancer have been reported in our BCDS cases. Functional experiments reported here indicated the BCDS variants comprise a distinct class of CDH1 variants. Altogether, we identified the genetic cause of BCDS enabling DNA diagnostics and counseling, in addition we describe a novel class of dominant negative CDH1 variants.
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Bamashmus, M A; Downey, L M; Inglehearn, C F; Gupta, S R; Mansfield, D C
2000-04-01
Familial exudative vitreoretinopathy (FEVR) is associated with mutations in the Norrie disease gene in X linked pedigrees and with linkage to the EVR1 locus at 11q13 in autosomal dominant cases. A large autosomal dominant FEVR family was studied, both clinically and by linkage analysis, to determine whether it differed from the known forms of FEVR. Affected members and obligate gene carriers from this family were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and in some cases fluorescein angiography. Patient DNAs were genotyped for markers at the EVR1 locus on chromosome 11q13. The clinical evaluation in this family is consistent with previous descriptions of FEVR pedigrees, but linkage analysis proves that it has a form of FEVR genetically distinct from the EVR1 locus on 11q. This proves that there are at least three different loci associated with comparable FEVR phenotypes, a situation similar to that existing for many forms of retinal degeneration.
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NASA Astrophysics Data System (ADS)
Slamet, Isnandar; Mardiana Putri Carissa, Siska; Pratiwi, Hasih
2017-10-01
Investors always seek an efficient portfolio which is a portfolio that has a maximum return on specific risk or minimal risk on specific return. Almost marginal conditional stochastic dominance (AMCSD) criteria can be used to form the efficient portfolio. The aim of this research is to apply the AMCSD criteria to form an efficient portfolio of bank shares listed in the LQ-45. This criteria is used when there are areas that do not meet the criteria of marginal conditional stochastic dominance (MCSD). On the other words, this criteria can be derived from quotient of areas that violate the MCSD criteria with the area that violate and not violate the MCSD criteria. Based on the data bank stocks listed on LQ-45, it can be stated that there are 38 efficient portfolios of 420 portfolios where each portfolio comprises of 4 stocks and 315 efficient portfolios of 1710 portfolios with each of portfolio has 3 stocks.
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A dominantly inherited form of arthrogryposis multiplex congenita with unusual dermatoglyphics.
Sack, G H
1978-12-01
A father and daughter with arthrogryposis multiplex congenita and similar dermatoglyphic patterns are described. No evidence was found of chromosomal abnormality, neuropathy or myopathy, and there were no other affected family members. The findings are compatible with autosomal dominant inheritance.
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Skórska, Czesława; Sitkowska, Jolanta; Krysińska-Traczyk, Ewa; Cholewa, Grazyna; Dutkiewicz, Jacek
2005-01-01
The aim of this study was to determine the levels of microorganisms, dust and endotoxin in the air during processing of peppermint (Mentha piperita) and chamomile (Matricaria recutita) by herb farmers, and to examine the species composition of airborne microflora. Air samples were collected on glass fibre filters by use of personal samplers on 13 farms owned by herb cultivating farmers, located in Lublin province (eastern Poland). The concentrations of total viable microorganisms (bacteria + fungi) in the farm air during processing of peppermint herb were large, within a range from 895.1-6,015.8 x 10(3) cfu/m(3) (median 1,055.3 x 10(3) cfu/m(3)). During processing of chamomile herb they were much lower and varied within a range from 0.88-295.6 x 10(3) cfu/m(3) (median 27.3 x 10(3) cfu/m(3)). Gram-negative bacteria distinctly prevailed during processing of peppermint leaves, forming 46.4-88.5 % of the total airborne microflora. During processing of chamomile herb, Gram-negative bacteria were dominant at 3 out of 6 sampling sites forming 54.7-75.3 % of total microflora, whereas at the remaining 3 sites the most common were fungi forming 46.2-99.9 % of the total count. The species Pantoea agglomerans (synonyms: Erwinia herbicola, Enterobacter agglomerans ), having strong allergenic and endotoxic properties, distinctly prevailed among Gram-negative isolates. Among fungi, the most common species was Alternaria alternata. The concentrations of airborne dust and endotoxin determined on the examined herb farms were large. The concentrations of airborne dust during peppermint and chamomile processing ranged from 86.7-958.9 mg/m(3), and from 1.1-499.2 mg/m(3), respectively (medians 552.3 mg/m(3) and 12.3 mg/m(3)). The concentrations of airborne endotoxin determined during peppermint and chamomile processing were within a wide range 1.53-208.33 microg/m(3) and 0.005-2604.19 microg/m(3) respectively (medians 57.3 microg/m(3) and 0.96 microg/m(3)). In conclusion, farmers cultivating peppermint are exposed during processing of this herb to large concentrations of airborne microorganisms, dust and endotoxin posing a risk of work-related respiratory disease. The exposure to bioaerosols during processing of chamomile is lower; nevertheless, peak values create a respiratory risk for exposed farmers.
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da Cunha, Leonardo Fernandes; Gonzaga, Carla Castiglia; Saab, Rafaella; Mushashe, Amanda Mahammad; Correr, Gisele Maria
2015-01-01
Central dominance is an important element of an esthetic smile. Color, form, and size have been suggested as tools for assessing the dominance of maxillary teeth. A spectrophotometer can be used to determine the value, hue, and chroma. Correct sizing of restorations according to the central incisor dominance principle improves not only esthetics but also aspects of occlusion, such as anterior guidance. Refractory porcelain systems can effectively restore the color, shape, emergence profile, and incisal translucency. This report illustrates the esthetic and occlusal rehabilitation of the dominance of maxillary central incisors using fabricated minimal thickness refractory porcelain veneers.
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NASA Astrophysics Data System (ADS)
McEnroe, S. A.; Robinson, P.
2012-12-01
The magnetic response of crustal rocks is directly related to type and abundance of oxides in the rock bodies. About 800 samples from mafic bodies and mantle peridotites from the eclogite-facies part of the Western Gneiss Region, Norway, were studied for magnetic properties and oxide mineralogy, and show strong variations. Many eclogites are paramagnetic, while adjacent gabbros from which the eclogites were derived during high-pressure (HP) recrystallization, either preserved or formed magnetite during HP metamorphism or during the following exhumation. Phase petrology indicates many of these rocks were subjected to 4 Gpa and possibly to 6 Gpa equivalent to depths of 125 and 200 km during the Scandian (Upper Silurian - Lower Devonian) continental subduction. Likely conditions in intermediate stages of exhumation were temperature (T) > 700C and pressure (P) of 1 GPa. When magnetite dominates in these samples, the primary control on magnetization is abundance, because magnetite in coarse-grained igneous and high-grade metamorphic rocks is commonly of multi-domain size, close to end-member, and with few microstructures. With few features to stabilize the NRM, the magnetic response is dominated by induced magnetization (Ji). When exsolved members of the rhombohedral ilmenite-hematite solid solution are present, commonly in more oxidized rocks, the response is dominated by the NRM (Jr), and NRM intensity is more complicated than in magnetite-bearing rocks. Important here, in addition to the amount of oxide, are the orientation of the oxide grains relative to the magnetizing field, and the amount of exsolution lamellae, mostly produced during cooling from HP conditions, leading to lamellar magnetism. Where there is no coexisting magnetite, these rocks have high Q values (Jr/Ji) because the induced magnetization (Ji) is low. For such more oxidized rocks, remanent anomalies are generally more common than for more reduced magnetite-bearing rocks formed under the same conditions. Mafic rocks from the Southwest Swedish Granulite Region contain high-pressure granulite-facies assemblages produced during Sveconorwegian (early Neoproterozoic) metamorphism with peak T of 770C and P 0.75-1.05 GPa. Here, the assemblages commonly indicate more oxidized compositions than prevailing in the Western Gneiss Region. Thus, the NRM is dominant, and resultant magnetic vectors are controlled by NRM vectors, nearly opposite to the Earth's present magnetic field, giving rise to striking negative anomalies. Both regions offer insights and show strong variations in the magnetic properties of lower crustal rocks.
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Karaca, Ender; Yuregir, Ozge O; Bozdogan, Sevcan T; Aslan, Huseyin; Pehlivan, Davut; Jhangiani, Shalini N; Akdemir, Zeynep C; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M; Erdin, Serkan; Muzny, Donna; Gibbs, Richard A; Lupski, James R
2015-11-01
Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in addition-from a mechanistic standpoint-suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lopes-Cendes, I.; Mulley, J.C.; Andermann, E.
1994-09-01
Recently, six families with a familial form of partial epilepsy were described. All pedigrees showed autosomal dominant inheritance with incomplete penetrance. Affected individuals present with predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates in an autosomal dominant fashion and has been localized to a region distal to the centromere of mouse chromosome 9. Comparative genetic maps between man and mouse have been used for prediction of localization of several human disease genes. Because the region ofmore » mouse chromosome 9 that is the most likely to contain the El-1 locus is syntenic to regions on human chromosomes 3q21-p22, 3q21-q23.3, 6q12 and 15q24, we adopted the candidate gene approach as an initial linkage strategy. Twenty-two polymorphic microsatellite markers covering these regions were used for genotyping individuals in the three larger families ascertained, two of which are Australian and one French-Canadian. Negative two-point lod scores were obtained separately for each family. The analysis of all three families combined significantly excludes the candidate regions on chromosomes 3, 6 and 15.« less
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Compositional variation in minerals of the chevkinite group
Macdonald, R.; Belkin, H.E.
2002-01-01
The composition of chevkinite and perrierite, the most common members of the chevkinite group, is closely expressed by the formula A4BC2D2Si4O22, where A = (La,Ce,Ca,Sr,Th), B = Fe2+, C = (Fe2+,Fe3+,Ti,Al,Zr,Nb) and D = Ti. The A site is dominated by a strong negative correlation between (Ca+Sr) and the REE. Chondrite-normalized REE patterns are very variable, e.g. in LREE/HREE and Eu/Eu*. The C site is dominated by Ti, Al and Fe2+, in very variable proportions. Most chevkinites and perrierites are close to stoichiometric, with cation sums between 12.9 and 13.5, compared to the theoretical 13. There is no single, generally applicable charge balancing substitution scheme in the group; however, the general relationship (Ca+Sr)A + TiC + REEA + M3C+2+ defines a linear array with r2 = 0.91. Chevkinite and perrierite are shown to be compositionally distinct on the basis of CaO, FeO* Al2O3 and Ce2O3 abundances. Chevkinite forms mainly in chemically evolved parageneses, such as syenites, rhyolites and fenites associated with carbonatite complexes. Perrierite is more commonly recorded from igneous rocks of mafic to intermediate composition. The compositional characteristics and possible structural formulae of other members of the chevkinite group are reviewed briefly.
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García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.
2015-01-01
Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422
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PAUL, ARCO P.; MEDINA, ALEXANDRE E.
2012-01-01
Neuronal plasticity deficits underlie many of the cognitive problems seen in Fetal Alcohol Spectrum Disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF−) or control GFP. After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF− or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD. PMID:22742904
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Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Ritelli, Marco
2018-01-01
Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM) organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition into the ECM of several structural proteins crucial to the integrity of soft connective tissues. PMID:29346445
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Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Ritelli, Marco; Colombi, Marina
2018-01-01
Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM) organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition into the ECM of several structural proteins crucial to the integrity of soft connective tissues.
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Cortez, IbDanelo; Bulavin, Dmitry V.; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T
2018-01-01
A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38αAF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38αAF/+) and kinase activity. As a result, aged DN-p38αAF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer’s disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual’s relative risk. In the present study, we evaluated aged DN-p38αAF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38αAF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38αAF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38αAF/+, we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38αAF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. PMID:27765672
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wolff, Natascha A.; Lee, Wing-Kee; Abouhamed, Marouan
2008-07-01
Filtered metal-protein complexes, such as cadmium-metallothionein-1 (CdMT-1) or transferrin (Tf) are apically endocytosed partly via megalin/cubilin by kidney proximal tubule (PT) cells where CdMT-1 internalization causes apoptosis. Small GTPase ARF (ADP-ribosylation factor) proteins regulate endocytosis and vesicular trafficking. We investigated roles of ARF6, which has been shown to be involved in internalization of ligands and endocytic trafficking in PT cells, following MT-1/CdMT-1 and Tf uptake by PT cells. WKPT-0293 Cl.2 cells derived from rat PT S1 segment were transfected with hemagglutinin-tagged wild-type (ARF6-WT) or dominant negative (ARF6-T27N) forms of ARF6. Using immunofluorescence, endogenous ARF6 was associated with the plasma membranemore » (PM) as well as juxtanuclear and co-localized with Rab5a and Rab11 involved in early and recycling endosomal trafficking. Immunofluorescence staining of megalin showed reduced surface labelling in ARF6 dominant negative (ARF6-DN) cells. Intracellular Alexa Fluor 546-conjugated MT-1 uptake was reduced in ARF6-DN cells and CdMT-1 (14.8 {mu}M for 24 h) toxicity was significantly attenuated from 27.3 {+-} 3.9% in ARF6-WT to 11.1 {+-} 4.0% in ARF6-DN cells (n = 6, P < 0.02). Moreover, reduced Alexa Fluor 546-conjugated Tf uptake was observed in ARF-DN cells (75.0 {+-} 4.6% versus 3.9 {+-} 3.9% of ARF6-WT cells, n = 3, P < 0.01) and/or remained near the PM (89.3 {+-} 5. 6% versus 45.2 {+-} 14.3% of ARF6-WT cells, n = 3, P < 0.05). In conclusion, the data support roles for ARF6 in receptor-mediated endocytosis and trafficking of MT-1/Tf to endosomes/lysosomes and CdMT-1 toxicity of PT cells.« less
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Abe, Tomoyuki; Kato, Masayoshi; Miki, Hiroaki; Takenawa, Tadaomi; Endo, Takeshi
2003-01-01
Rho family small GTPases regulate multiple cellular functions through reorganization of the actin cytoskeleton. Among them, Cdc42 and Tc10 induce filopodia or peripheral processes in cultured cells. We have identified a member of the family, designated as RhoT, which is closely related to Tc10. Tc10 was highly expressed in muscular tissues and brain and remarkably induced during differentiation of C2 skeletal muscle cells and neuronal differentiation of PC12 and N1E-115 cells. On the other hand, RhoT was predominantly expressed in heart and uterus and induced during neuronal differentiation of N1E-115 cells. Tc10 exogenously expressed in fibroblasts generated actin-filament-containing peripheral processes longer than the Cdc42-formed filopodia, whereas RhoT produced much longer and thicker processes containing actin filaments. Furthermore, both Tc10 and RhoT induced neurite outgrowth in PC12 and N1E-115 cells, but Cdc42 did not do this by itself. Tc10 and RhoT as well as Cdc42 bound to the N-terminal CRIB-motif-containing portion of N-WASP and activated N-WASP to induce Arp2/3-complex-mediated actin polymerization. The formation of peripheral processes and neurites by Tc10 and RhoT was prevented by the coexpression of dominant-negative mutants of N-WASP. Thus, N-WASP is essential for the process formation and neurite outgrowth induced by Tc10 and RhoT. Neuronal differentiation of PC12 and N1E-115 cells induced by dibutyryl cyclic AMP and by serum starvation, respectively, was prevented by dominant-negative Cdc42, Tc10 and RhoT. Taken together, all these Rho family proteins are required for neuronal differentiation, but they exert their functions differentially in process formation and neurite extension. Consequently, N-WASP activated by these small GTPases mediates neuronal differentiation in addition to its recently identified role in glucose uptake.
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Sundararaj, Kamala; Pleasant, Dorea L; Moschella, Phillip C; Panneerselvam, Kavin; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani
2016-02-01
Connective tissue growth factor (CTGF) is a fibrogenic cytokine that promotes fibrosis in various organs. In the heart, both cardiomyocytes (CM) and cardiac fibroblasts have been reported as a source of CTGF expression, aiding cardiac fibrosis. Although the mammalian target of rapamycin (mTOR) forms 2 distinct complexes, mTORC1 and mTORC2, and plays a central role in integrating biochemical signals for protein synthesis and cellular homeostasis, we explored its role in CTGF expression in adult feline CM. CM were stimulated with 10 μM phenylephrine (PE), 200 nM angiotensin (Ang), or 100 nM insulin for 24 hours. PE and Ang, but not insulin, caused an increase in CTGF mRNA expression with the highest expression observed with PE. Inhibition of mTOR with torin1 but not rapamycin significantly enhanced PE-stimulated CTGF expression. Furthermore, silencing of raptor and rictor using shRNA adenoviral vectors to suppress mTORC1 and mTORC2, respectively, or blocking phosphatidylinositol 3-kinase (PI3K) signaling with LY294002 (LY) or Akt signaling by dominant-negative Akt expression caused a substantial increase in PE-stimulated CTGF expression as measured by both mRNA and secreted protein levels. However, studies with dominant-negative delta isoform of protein kinase C demonstrate that delta isoform of protein kinase C is required for both agonist-induced CTGF expression and mTORC2/Akt-mediated CTGF suppression. Finally, PE-stimulated CTGF expression was accompanied with a corresponding increase in Smad3 phosphorylation and pretreatment of cells with SIS3, a Smad3 specific inhibitor, partially blocked the PE-stimulated CTGF expression. Therefore, a PI3K/mTOR/Akt axis plays a suppressive role on agonist-stimulated CTGF expression where the loss of this mechanism could be a contributing factor for the onset of cardiac fibrosis in the hypertrophying myocardium.
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Kong, M; Mounier, C; Wu, J; Posner, B I
2000-11-17
In previous work we showed that the phosphatidylinositol 3-kinase (PI3-kinase), not the mitogen-activated protein kinase, pathway is necessary and sufficient to account for insulin- and epidermal growth factor (EGF)-induced DNA synthesis in rat hepatocytes. Here, using a dominant-negative p85, we confirmed the key role of EGF-induced PI3-kinase activation and sought to identify the mechanism by which this is effected. Our results show that EGF activates PI3-kinase with a time course similar to that of the association of p85 with three principal phosphotyrosine proteins (i. e. PY180, PY105, and PY52). We demonstrated that each formed a distinct p85-associated complex. PY180 and PY52 each constituted about 10% of EGF-activated PI3-kinase, whereas PY105 was responsible for 80%. PY105 associated with Grb2 and SHP-2, and although it behaved like Gab1, none of the latter was detected in rat liver. We therefore cloned a cDNA from rat liver, which was found to be 95% homologous to the mouse Grb2-associated binder 2 (Gab2) cDNA sequence. Using a specific Gab2 antibody, we demonstrated its expression in and association with p85, SHP-2, and Grb2 upon EGF treatment of rat hepatocytes. Gab2 accounted for most if not all of the PY105 species, since immunoprecipitation of Gab2 with specific antibodies demonstrated parallel immunodepletion of Gab2 and PY105 from the residual supernatants. We also found that the PI3-kinase activity associated with Gab2 was totally abolished by dominant negative p85. Thus, Gab2 appears to be the principal EGF-induced PY protein recruiting and activating PI3-kinase and mitogenesis.
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Elzarrad, M Khair; Haroon, Abu; Willecke, Klaus; Dobrowolski, Radoslaw; Gillespie, Mark N; Al-Mehdi, Abu-Bakr
2008-01-01
Background The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium. Methods Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function. Results Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci. Conclusion Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis. PMID:18647409
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Elzarrad, M Khair; Haroon, Abu; Willecke, Klaus; Dobrowolski, Radoslaw; Gillespie, Mark N; Al-Mehdi, Abu-Bakr
2008-07-22
The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium. Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function. Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci. Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis.
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Berger, J; Patel, H V; Woods, J; Hayes, N S; Parent, S A; Clemas, J; Leibowitz, M D; Elbrecht, A; Rachubinski, R A; Capone, J P; Moller, D E
2000-04-25
The peroxisomal proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that act as ligand-activated transcription factors. PPARgamma plays a critical role in regulating adipocyte differentiation and lipid metabolism. Recently, thiazolidinedione (TZD) and select non-TZD antidiabetic agents have been identified as PPARgamma agonists. To further characterize this receptor subclass, a mutant hPPARgamma lacking five carboxyl-terminal amino acids was produced (hPPARgamma2Delta500). In COS-1 cells transfected with PPAR-responsive reporter constructs, the mutant receptor could not be activated by a potent PPARgamma agonist. When cotransfected with hPPARgamma2 or hPPARalpha, hPPARgamma2Delta500 abrogated wild-type receptor activity in a dose-responsive manner. hPPARgamma2Delta500 was also impaired with respect to binding of a high-affinity radioligand. In addition, its conformation was unaffected by normally saturating concentrations of PPARgamma agonist as determined by protease protection experiments. Electrophoretic mobility shift assays demonstrated that hPPARgamma2Delta500 and hPPARgamma2 both formed heterodimeric complexes with human retinoidxreceptor alpha (hRXRalpha) and could bind a peroxisome proliferator-responsive element (PPRE) with similar affinity. Therefore, hPPARgamma2Delta500 appears to repress PPAR activity by competing with wild type receptor to dimerize with RXR and bind the PPRE. In addition, the mutant receptor may titrate out factors required for PPAR-regulated transcriptional activation. Both hPPARgamma2 and hPPARgamma2Delta500 localized to the nucleus of transiently transfected COS-1 cells as determined by immunofluorescence using a PPARgamma-specific antibody. Thus, nuclear localization of PPARgamma occurs independently of its activation state. The dominant negative mutant, hPPARgamma2Delta500, may prove useful in further studies to characterize PPAR functions both in vitro and in vivo
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Expression and Function of Xmsx-2B in Dorso-Ventral Axis Formation in Gastrula Embryos.
Onitsuka, I; Takeda, M; Maéno, M
2000-11-01
Msx is a homeodomain-containing transcriptional factor that plays an essential role in pattern formation in vertebrata and invertebrata embryos. In Xenopus laevis, two msx genes have been identified (Xmsx-1 and Xmsx-2). In the present study, we attempted to elucidate the expression and function of Xmsx-2B (formerly designated as Xhox7.1') in early embryogenesis. Whole mount in situ hybridization analyses showed that the expression pattern of Xmsx-2B at gastrula and neurula stages was very similar to that of Xmsx-1: the transcript of Xmsx-2B was observed in ventral and lateral sides of the embryo. At the tailbud stage, however, the expression pattern of Xmsx-2B in neural tissues was distinct from that of Xmsx-1. An RNA injection experiment revealed that, like BMP-4, Xmsx-2B has a strong ventralizing activity. In the Xmsx-2B -injected embryos, differentiation of axial structures such as the notochord, muscle, and neural tissue was completely suppressed, whereas alpha-globin mRNA, a blood cell marker, was highly expressed. Simultaneous injection of Xmsx-1 and Xmsx-2B RNAs showed that they function in an additive manner. It was also shown that coinjection of Xmsx-2B with a dominant-negative BMP-4 receptor (tBR), which can induce formation of secondary axis when injected alone in ventral blastomeres, suppressed secondary axis formation. Furthermore, Xmsx-2B also suppressed secondary axis formation, which was induced by a dominant-negative form of Xmsx-1 (VP16/msx-1). Therefore, like Xmsx-1, Xmsx-2B is a downstream nuclear factor of the BMP-4-derived ventralizing signal, and these two factors probably share the same target molecules. In conclusion, Xmsx-1 and Xmsx-2B function in dorso-ventral axis formation in early Xenopus laevis development.
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Cortez, IbDanelo; Bulavin, Dmitry V; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T
2017-03-30
A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α AF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α AF/+ ) and kinase activity. As a result, aged DN-p38α AF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer's disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual's relative risk. In the present study, we evaluated aged DN-p38α AF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38α AF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38α AF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38α AF/+ , we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38α AF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. Copyright © 2016 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Ejarque, Ana; Anderson, R. Scott; Simms, Alexander R.; Gentry, Beau J.
2015-03-01
Using a novel combination of paleoecologic proxies including pollen, non-pollen palynomorphs (NPPs), macroscopic charcoal, and Spheroidal Carbonaceous Particles (SCPs), 5000 years of landscape change, fire history and land-use have been reconstructed from Dune Pond, Santa Barbara County, California. The pond was sensitive to Holocene regional climatic variability, showing different phases of lower (4600-3700 cal yr BP, 2100-700 cal yr BP, historical period) and higher (3700-2100 cal yr BP, 700-150 cal yr BP) local moisture availability. During this period the landscape was dominated by a coastal mosaic vegetation including dune mats, coastal scrub and salt marshes on the dunes and backdunes, with chaparral and oak woodland growing in the valley plains and foothills. Fire was intimately linked with such dominating mosaic vegetation, and the combination of wet conditions and the presence of nearby human settlement were a trigger favoring coastal fires for at least two periods: from 3100 to 1500 cal yr BP and from 650 cal yr BP until the 18th century. In both cases fire was an important tool to keep an open coastal landscape attractive to hunting wildlife. Finally, matching this varied range of high-resolution paleoecological proxies with historical records we could characterize the development of colonial transported landscapes following the Euro-American settlement of Santa Barbara. The introduction of livestock grazing by Spanish colonists favored erosive processes and the introduction of fecal-borne parasites in freshwater bodies, negatively impacted salt and brackish coastal marshes, and promoted the invasion of alien grasses and ruderals. This agro-pastoral landscape was consolidated during the American period, with a greater role for cultivation, the development of industrial activities and increased population. Despite negative environmental consequences such as the loss of native habitats, exotic land-uses and plants introduced during the historical period significantly contributed to the configuration of a cultural landscape which forms part of the cultural heritage of California.
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Farhat, Katja; Riekenberg, Sabine; Heine, Holger; Debarry, Jennifer; Lang, Roland; Mages, Jörg; Buwitt-Beckmann, Ute; Röschmann, Kristina; Jung, Günther; Wiesmüller, Karl-Heinz; Ulmer, Artur J
2008-03-01
TLR are primary triggers of the innate immune system by recognizing various microorganisms through conserved pathogen-associated molecular patterns. TLR2 is the receptor for a functional recognition of bacterial lipopeptides (LP) and is up-regulated during various disorders such as chronic obstructive pulmonary disease and sepsis. This receptor is unique in its ability to form heteromers with TLR1 or TLR6 to mediate intracellular signaling. According to the fatty acid pattern as well as the assembling of the polypeptide tail, LP can signal through TLR2 in a TLR1- or TLR6-dependent manner. There are also di- and triacylated LP, which stimulate TLR1-deficient cells and TLR6-deficient cells. In this study, we investigated whether heterodimerization evolutionarily developed to broaden the ligand spectrum or to induce different immune responses. We analyzed the signal transduction pathways activated through the different TLR2 dimers using the three LP, palmitic acid (Pam)octanoic acid (Oct)(2)C-(VPGVG)(4)VPGKG, fibroblast-stimulating LP-1, and Pam(2)C-SK(4). Dominant-negative forms of signaling molecules, immunoblotting of MAPK, as well as microarray analysis indicate that all dimers use the same signaling cascade, leading to an identical pattern of gene activation. We conclude that heterodimerization of TLR2 with TLR1 or TLR6 evolutionarily developed to expand the ligand spectrum to enable the innate immune system to recognize the numerous, different structures of LP present in various pathogens. Thus, although mycoplasma and Gram-positive and Gram-negative bacteria may activate different TLR2 dimers, the development of different signal pathways in response to different LP does not seem to be of vital significance for the innate defense system.
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Positive and Negative Aspects of the Dominance of English.
ERIC Educational Resources Information Center
Master, Peter
1998-01-01
Maintains that because the field of English for specific purposes deals with the language of science, technology, and business, it is in a pivotal position regarding the use or abuse of linguistic power. (Author/VWL)
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LeBreton, James M.; Baysinger, Michael; Abbey, Antonia; Jacques-Tiura, Angela J.
2013-01-01
This paper reports the relative contributions of several facets of subclinical psychopathy (i.e., callous affect, erratic lifestyle, interpersonal manipulation), subclinical narcissism (i.e., entitlement, exploitation), and trait aggression (i.e., anger) to the prediction of four enduring attitudes towards women and sexual assault (i.e., hostility towards women, negative attitudes regarding women, sexual dominance, impersonal sex) and a behavioral indicator of an impersonal sexual behavior (i.e., number of one-night stands). Survey data were collected from 470 single men living in the Detroit Metropolitan area. The importance of personality traits varied as a function of the outcome with anger most predictive of hostility toward women; erratic lifestyle most predictive of impersonal sexual attitudes and behavior, and entitlement most predictive of sexual dominance and negative attitudes toward women. These outcome-specific findings are interpreted and directions for future research are discussed. PMID:26082565
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Motherhood and the Wages of Women in Professional Occupations.
Buchmann, Claudia; McDaniel, Anne
2016-08-01
It is well established that mothers are paid less than childless women and that fathers tend to earn higher wages relative to childless men, but we do not know whether these findings apply to workers in all occupations. Using IPUMS and ACS data from 1980 and 2010, we examine the family wage gap for highly educated professionals, the most advantaged sector of the occupational distribution. Results indicate that the size of the negative wage differential for motherhood has declined over time in all professions. Moreover, in the traditionally male-dominated professions of STEM, medicine, and law, women with children experience a positive wage differential, whereas their counterparts in female-dominated professions continue to experience a negative one. The positive differential for fatherhood has remained stable over time. These findings underscore the growing heterogeneity of women's experiences in combining work and family and raise important questions for further research.
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Motherhood and the Wages of Women in Professional Occupations
BUCHMANN, CLAUDIA; MCDANIEL, ANNE
2017-01-01
It is well established that mothers are paid less than childless women and that fathers tend to earn higher wages relative to childless men, but we do not know whether these findings apply to workers in all occupations. Using IPUMS and ACS data from 1980 and 2010, we examine the family wage gap for highly educated professionals, the most advantaged sector of the occupational distribution. Results indicate that the size of the negative wage differential for motherhood has declined over time in all professions. Moreover, in the traditionally male-dominated professions of STEM, medicine, and law, women with children experience a positive wage differential, whereas their counterparts in female-dominated professions continue to experience a negative one. The positive differential for fatherhood has remained stable over time. These findings underscore the growing heterogeneity of women’s experiences in combining work and family and raise important questions for further research. PMID:29177191
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Owuamalam, Chuma; Zagefka, Hanna
2013-11-01
This article examines the implications of perceived negativity from members of a dominant outgroup on the world views and perceived relative group worth of members of disadvantaged groups. We hypothesized that concerns about the negative opinions a dominant outgroup is perceived to hold of the ingroup (i.e., meta-stereotypes) would undermine group members' views about societal fairness. We expected this trend to be mediated by recall of previous personal experiences of discrimination. We further hypothesized that members' views about societal fairness would predict their perception of the ingroup's worth relative to the outgroup - such that undermined views about societal fairness would be associated with lower perceived ingroup worth relative to the outgroup. Taken jointly, results from two studies using two real intergroup contexts support these hypotheses and are discussed in terms of their implications for the social mobility of members of disadvantaged groups. © 2012 The British Psychological Society.
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Negative ion source with hollow cathode discharge plasma
Hershcovitch, A.; Prelec, K.
1980-12-12
A negative ion source of the type where negative ions are formed by bombarding a low-work-function surface with positive ions and neutral particles from a plasma, wherein a highly ionized plasma is injected into an anode space containing the low-work-function surface is described. The plasma is formed by hollow cathode discharge and injected into the anode space along the magnetic field lines. Preferably, the negative ion source is of the magnetron type.
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Owrangi, B; Masters, N; Vollmerhausen, T L; O'Dea, C; Kuballa, A; Katouli, M
2017-04-01
Escherichia coli strains are normal inhabitants of the gut and are normally found in the faeces of the host at different population sizes. We characterised faecal E. coli of 45 healthy male (n = 17) and female (n = 28) volunteers by testing 28 isolates from each individual. These isolates were typed and divided into dominant (if constituted >50% of the population tested) and non-dominant types in each individual. Representative strains of each dominant and non-dominant type were tested for their virulence gene profiles, their ability to form biofilm, adhere to, invade and translocate through a gut epithelial cell line (Caco-2 cells). Strains belonging to dominant types adhered significantly more to Caco-2 cells than non-dominant strains (5.7 ± 0.3 versus 4.3.± 0.13 CFU/cell mean ± SEM, P = 0.0003). They also invaded (135 ± 6 versus 63 ± 13 CFU) and translocated through Caco-2 cells (84 ± 5 versus 32 ± 9 CFU) significantly more than non-dominant strains (P < 0.0001 and P = 0.0002, respectively). Moreover, dominant strains showed the ability to form significantly more biofilm than non-dominant strains (1.1 ± 0.01 versus 0.5 ± 0.1 OD 600 , P < 0.0001). Majority (51%) of the strains belonged to phylogroup D followed by B2 (23%). Furthermore, out of 25 virulence genes tested, kpsMTII, papC and papG allele III were found to be significantly higher among dominant than non-dominant strains. Our results suggest that E. coli strains dominating the gut may have virulence properties that enable them to efficiently interact with the gut epithelium and translocate under predisposing conditions of the host. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Genesis of iron-apatite ores in Posht-e-Badam Block (Central Iran) using REE geochemistry
NASA Astrophysics Data System (ADS)
Mokhtari, Mir Ali Asghar; Zadeh, Ghader Hossein; Emami, Mohamad Hashem
2013-06-01
Rare earth elements in apatites of different ore types show characteristic patterns which are related to different modes of formation of the ores. Most of the apatite-bearing iron ores are associated with alkaline magmas with LREE/HREE fractionation varying from moderate to steep. Iron-apatite deposits in Posht-e-Badam Block (Central Iran) have a high concentration of REE (more than 1000 ppm up to 2.5%), and show a strong LREE/HREE ratio with a pronounced negative Eu anomaly. This REE pattern is typical of magmatic apatite and quiet distinct from sedimentary apatites (phosphorites) which have a low REE contents and Ce negative anomalies. On the other hand, they are comparable to the REE patterns of apatites in Kiruna-type iron ores in different parts of the world. The REE patterns of apatites, iron-apatite ores and iron ores are similar and only have different REE contents. This similarity indicates a genetic relation for these rocks. Most of the iron-apatite deposits in Central Iran have similar REE patterns too, which in turn show a genetic relation for all of these deposits. This similarity indicates a similar origin and processes in their genesis. There are some small intrusions around some of the iron-apatite deposits that are petrographically identified as syenite and gabbro. These intrusions also have REE patterns similar to that of iron-apatite ores. This demonstrates a genetic relation between these intrusions and iron-apatite ores. The REE patterns of apatites in different deposits of Posht-e-Badam Block iron-apatite ores show an affinity to alkaline to sub-alkaline magmas and rifting environment. The alkaline host rocks of Central Iran iron-apatite ores are clearly related to an extensional setting where rifting was important (SSE-NNW fault lines). A probable source for this large scale ore forming processes is relatively low partial melting of mantle rocks. The ores have originated by magmatic differentiation as a late phase in the volcanic cycle forming sub-surface injections or surface flows. These ores have formed during magmatism as immiscible liquids (silicate and Fe-P-rich magmatic liquids) which separated from strongly differentiated magmas aided by a large volatile and alkali element content. Separation of an iron oxide melt and the ensuing hydrothermal processes dominated by alkali metasomatism were both involved to different degrees in the formation of Posht-e-Badam Block iron-apatite deposits. We proposed that the separation of an iron oxide melt and the ensuing hydrothermal processes dominated by alkali metasomatism were both involved to different degrees in the formation of Posht-e-Badam Block iron-apatite deposits.
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Genetic forms of neurohypophyseal diabetes insipidus.
Rutishauser, Jonas; Spiess, Martin; Kopp, Peter
2016-03-01
Neurohypophyseal diabetes insipidus is characterized by polyuria and polydipsia owing to partial or complete deficiency of the antidiuretic hormone, arginine vasopressin (AVP). Although in most patients non-hereditary causes underlie the disorder, genetic forms have long been recognized and studied both in vivo and in vitro. In most affected families, the disease is transmitted in an autosomal dominant manner, whereas autosomal recessive forms are much less frequent. Both phenotypes can be caused by mutations in the vasopressin-neurophysin II (AVP) gene. In transfected cells expressing dominant mutations, the mutated hormone precursor is retained in the endoplasmic reticulum, where it forms fibrillar aggregates. Autopsy studies in humans and a murine knock-in model suggest that the dominant phenotype results from toxicity to vasopressinergic neurons, but the mechanisms leading to cell death remain unclear. Recessive transmission results from AVP with reduced biologic activity or the deletion of the locus. Genetic neurohypophyseal diabetes insipidus occurring in the context of diabetes mellitus, optic atrophy, and deafness is termed DIDMOAD or Wolfram syndrome, a genetically and phenotypically heterogeneous autosomal recessive disorder caused by mutations in the wolframin (WFS 1) gene. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Valiente, Carlos; Eisenberg, Nancy; Shepard, Stephanie A; Fabes, Richard A; Cumberland, Amanda J; Losoya, Sandra H; Spinrad, Tracy L
2004-03-01
Guided by the heuristic model proposed by Eisenberg et al. [Psychol. Inq. 9 (1998) 241], we examined the relations of mothers' reported and observed negative expressivity to children's (N = 159; 74 girls; M age = 7.67 years) experience and expression of emotion. Children's experience and/or expression of emotion in response to a distressing film were measured with facial, heart rate, and self-report measures. Children's heart rate and facial distress were modestly positively related. Children's facial distress was significantly positively related to mothers' reports of negative (dominant and submissive) expressivity; the positive relation between children's facial distress and mothers' observed negative expressivity approached the conventional level of significance. Moreover, mothers' observed negative expressivity was significantly negatively related to children's heart rate reactivity during the conflict film. The positive relation between children's reported distress and mothers' observed negative expressivity approached the conventional level of significance. Several possible explanations for the pattern of findings are discussed.
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Valiente, Carlos; Eisenberg, Nancy; Shepard, Stephanie A.; Fabes, Richard A.; Cumberland, Amanda J.; Losoya, Sandra H.; Spinrad, Tracy L.
2010-01-01
Guided by the heuristic model proposed by Eisenberg et al. [Psychol. Inq. 9 (1998) 241], we examined the relations of mothers’ reported and observed negative expressivity to children’s (N = 159; 74 girls; M age = 7.67 years) experience and expression of emotion. Children’s experience and/or expression of emotion in response to a distressing film were measured with facial, heart rate, and self-report measures. Children’s heart rate and facial distress were modestly positively related. Children’s facial distress was significantly positively related to mothers’ reports of negative (dominant and submissive) expressivity; the positive relation between children’s facial distress and mothers’ observed negative expressivity approached the conventional level of significance. Moreover, mothers’ observed negative expressivity was significantly negatively related to children’s heart rate reactivity during the conflict film. The positive relation between children’s reported distress and mothers’ observed negative expressivity approached the conventional level of significance. Several possible explanations for the pattern of findings are discussed. PMID:20617103
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Forms of Social Support in the Workplace for Individuals with Visual Impairments
ERIC Educational Resources Information Center
Papakonstantinou, Doxa; Papadopoulos, Konstantinos
2010-01-01
In this study, the authors explored the forms of social support, both positive and negative, that individuals with visual impairments receive in the workplace. This study was a follow-up to the authors' previous study (Papakonstantinou & Papadopoulos, 2009) that investigated the various forms of positive and negative social support received by…
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Fauchald, Per; Langeland, Knut; Ims, Rolf A.; Yoccoz, Nigel G.; Bråthen, Kari Anne
2014-01-01
The spatial and temporal distribution of forage quality is among the most central factors affecting herbivore habitat selection. Yet, for high latitude areas, forage quantity has been found to be more important than quality. Studies on large ungulate foraging patterns are faced with methodological challenges in both assessing animal movements at the scale of forage distribution, and in assessing forage quality with relevant metrics. Here we use first-passage time analyses to assess how reindeer movements relate to forage quality and quantity measured as the phenology and cover of growth forms along reindeer tracks. The study was conducted in a high latitude ecosystem dominated by low-palatable growth forms. We found that the scale of reindeer movement was season dependent, with more extensive area use as the summer season advanced. Small-scale movement in the early season was related to selection for younger stages of phenology and for higher abundances of generally phenologically advanced palatable growth forms (grasses and deciduous shrubs). Also there was a clear selection for later phenological stages of the most dominant, yet generally phenologically slow and low-palatable growth form (evergreen shrubs). As the summer season advanced only quantity was important, with selection for higher quantities of one palatable growth form and avoidance of a low palatable growth form. We conclude that both forage quality and quantity are significant predictors to habitat selection by a large herbivore at high latitude. The early season selectivity reflected that among dominating low palatability growth forms there were palatable phenological stages and palatable growth forms available, causing herbivores to be selective in their habitat use. The diminishing selectivity and the increasing scale of movement as the season developed suggest a response by reindeer to homogenized forage availability of low quality. PMID:24972188
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Iversen, Marianne; Fauchald, Per; Langeland, Knut; Ims, Rolf A; Yoccoz, Nigel G; Bråthen, Kari Anne
2014-01-01
The spatial and temporal distribution of forage quality is among the most central factors affecting herbivore habitat selection. Yet, for high latitude areas, forage quantity has been found to be more important than quality. Studies on large ungulate foraging patterns are faced with methodological challenges in both assessing animal movements at the scale of forage distribution, and in assessing forage quality with relevant metrics. Here we use first-passage time analyses to assess how reindeer movements relate to forage quality and quantity measured as the phenology and cover of growth forms along reindeer tracks. The study was conducted in a high latitude ecosystem dominated by low-palatable growth forms. We found that the scale of reindeer movement was season dependent, with more extensive area use as the summer season advanced. Small-scale movement in the early season was related to selection for younger stages of phenology and for higher abundances of generally phenologically advanced palatable growth forms (grasses and deciduous shrubs). Also there was a clear selection for later phenological stages of the most dominant, yet generally phenologically slow and low-palatable growth form (evergreen shrubs). As the summer season advanced only quantity was important, with selection for higher quantities of one palatable growth form and avoidance of a low palatable growth form. We conclude that both forage quality and quantity are significant predictors to habitat selection by a large herbivore at high latitude. The early season selectivity reflected that among dominating low palatability growth forms there were palatable phenological stages and palatable growth forms available, causing herbivores to be selective in their habitat use. The diminishing selectivity and the increasing scale of movement as the season developed suggest a response by reindeer to homogenized forage availability of low quality.
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Interactive learning in 2×2 normal form games by neural network agents
NASA Astrophysics Data System (ADS)
Spiliopoulos, Leonidas
2012-11-01
This paper models the learning process of populations of randomly rematched tabula rasa neural network (NN) agents playing randomly generated 2×2 normal form games of all strategic classes. This approach has greater external validity than the existing models in the literature, each of which is usually applicable to narrow subsets of classes of games (often a single game) and/or to fixed matching protocols. The learning prowess of NNs with hidden layers was impressive as they learned to play unique pure strategy equilibria with near certainty, adhered to principles of dominance and iterated dominance, and exhibited a preference for risk-dominant equilibria. In contrast, perceptron NNs were found to perform significantly worse than hidden layer NN agents and human subjects in experimental studies.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Stenger, Drake C., E-mail: drake.stenger@ars.usda.
Population structure of Homalodisca coagulata Virus-1 (HoCV-1) among and within field-collected insects sampled from a single point in space and time was examined. Polymorphism in complete consensus sequences among single-insect isolates was dominated by synonymous substitutions. The mutant spectrum of the C2 helicase region within each single-insect isolate was unique and dominated by nonsynonymous singletons. Bootstrapping was used to correct the within-isolate nonsynonymous:synonymous arithmetic ratio (N:S) for RT-PCR error, yielding an N:S value ~one log-unit greater than that of consensus sequences. Probability of all possible single-base substitutions for the C2 region predicted N:S values within 95% confidence limits of themore » corrected within-isolate N:S when the only constraint imposed was viral polymerase error bias for transitions over transversions. These results indicate that bottlenecks coupled with strong negative/purifying selection drive consensus sequences toward neutral sequence space, and that most polymorphism within single-insect isolates is composed of newly-minted mutations sampled prior to selection. -- Highlights: •Sampling protocol minimized differential selection/history among isolates. •Polymorphism among consensus sequences dominated by negative/purifying selection. •Within-isolate N:S ratio corrected for RT-PCR error by bootstrapping. •Within-isolate mutant spectrum dominated by new mutations yet to undergo selection.« less
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Health Providers' Narratives on Intimate Partner Violence Against Roma Women in Spain.
Briones-Vozmediano, Erica; La Parra-Casado, Daniel; Vives-Cases, Carmen
2018-03-01
This qualitative study identifies health professionals' dominant, adaptive, and liberating narratives regarding inter-ethnic relations when talking about intimate partner violence (IPV) and the health system responses to the way it affects Roma women. Dominant narratives are oppressive internalized stories that shape social perceptions of members of both dominant and minority groups, adaptive narratives refer to those that acknowledge asymmetry and inequality, and liberating narratives directly challenge oppression with resistant views of stereotypes and negative interpretations. A total of 25 in-depth interviews were carried out with healthcare professionals in Spain in 2015. A discourse analysis of the interview transcriptions was conducted, showing the way in which different narratives about Roma people and IPV are combined among health providers. Dominant narratives were more salient: they were used by health providers to reflect prejudicial social perceptions in Spain that depict the Roma as a marginalized and traditional group, to construct Roma women in negative and prejudicial terms as patients, and to explain the existence of the cultural normalization of IPV among Roma women. Adaptive and liberating narratives showed a prevailing ideology in terms of the tendency to socially discriminate against Roma people. Using liberating narratives to train and raise awareness among health professionals about IPV among Roma women could facilitate a positive change in their treatment of Roma women who could be affected by IPV, helping to ameliorate the maintenance of existing prejudices. © Society for Community Research and Action 2018.
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Heart Rate Turbulence Parameters Correlate with Post-PVC Changes in Muscle Sympathetic Activity
Segerson, Nathan M.; Wasmund, Stephen L.; Abedin, Moeen; Pai, Rakesh K.; Daccarett, Marcos; Akoum, Nazem; Wall, T. Scott; Klein, Richard C.; Freedman, Roger A.; Hamdan, Mohamed H.
2007-01-01
Background Heart rate turbulence (HRT) has been shown to be vagally-mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) following a premature ventricular contraction (PVC) remains unclear. Objective We sought to evaluate the relationship between HRT and the changes in peripheral SNA following PVCs. Methods We recorded post-ganglionic muscle SNA during ECG monitoring in 8 patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during 1) the dominant burst following the PVC (Dominant-Burst Area), and 2) the 10 seconds following the dominant burst (Post-Burst SNA). Results The mean TO was 0.1±4.6% and the mean TS was 6.1±6.6. The Dominant-Burst Area negatively correlated with TO (-0.50, p=0.0002). The Post-Burst SNA showed a significant positive correlation with TO (r=0.44, p=0.001) and a negative correlation with TS (r=-0.42, p=0.002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. Conclusions Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease. PMID:17341389
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de Diego, Rebeca Pérez; Sancho-Shimizu, Vanessa; Lorenzo, Lazaro; Puel, Anne; Plancoulaine, Sabine; Picard, Capucine; Herman, Melina; Cardon, Annabelle; Durandy, Anne; Bustamante, Jacinta; Vallabhapurapu, Sivakumar; Bravo, Jerónimo; Warnatz, Klaus; Chaix, Yves; Cascarrigny, Françoise; Lebon, Pierre; Rozenberg, Flore; Karin, Michael; Tardieu, Marc; Al-Muhsen, Saleh; Jouanguy, Emmanuelle; Zhang, Shen-Ying; Abel, Laurent; Casanova, Jean-Laurent
2010-01-01
Tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) functions downstream of multiple receptors that induce interferon-α (IFN-α), IFN–β and IFN-λ production, including Toll-like receptor 3 (TLR3), which is deficient in some patients with herpes simplex virus-1 encephalitis (HSE). Mice lacking TRAF3 die in the neonatal period, preventing direct investigation of the role of TRAF3 in immune responses and host defenses in vivo. Here we reported the autosomal dominant, human TRAF3 deficiency in a young adult with a history of HSE in childhood. The TRAF3 mutant allele was a loss-of-expression, loss-of-function, dominant-negative phenotype, and was associated with impaired, but not abolished TRAF3-dependent responses upon stimulation of both TNF receptors and receptors that induce IFN production. TRAF3 deficiency was associated with a clinical phenotype limited to HSE resulting from the impairment of TLR3-dependent induction of IFN. Thus, TLR3-mediated immunity against primary infection by HSV-1 in the central nervous system is critically dependent on TRAF3. Highlight sentence Autosomal dominant TRAF3 deficiency is a genetic etiology of herpes simplex encephalitis. Highlight sentence R118W TRAF3 allele is loss-of-function, loss-of-expression, and dominant-negative. Highlight sentence Human TRAF3 deficiency impairs the TLR3-dependent induction of anti-viral interferons. PMID:20832341
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Role of hand dominance in mapping preferences for emotional-valence words to keypress responses.
Song, Xiaolei; Chen, Jing; Proctor, Robert W
2017-10-01
When a crossed-hands placement (right hand presses left key; left hand presses right key) is used in a two-choice spatial reaction task, the mapping of left stimulus to left key and right stimulus to right key yields faster responses than the opposite mapping. In contrast, de la Vega, Dudschig, De Filippis, Lachmair, and Kaup (2013) reported that when right-handed individuals classified words as having positive or negative affect, there was a benefit for mapping positive affect to the right hand (left key) and negative affect to the left hand (right key). The goal of the present study was to replicate and extend this seemingly distinct finding. Experiment 1 duplicated the design of that study without including nonword "no-go" trials but including a condition in which participants performed with an uncrossed hand placement. Results corroborated the benefit for mapping positive to the right hand and negative to the left hand with the hands crossed, and this benefit was as large as that obtained with the hands uncrossed. Experiment 2 confirmed the importance of the dominant/subordinate hand distinction with left-handed participants, and Experiment 3 showed, with right-handed participants, that it does not depend on which limb is placed over the other. The results verify that the mapping advantage for positive→right/negative→left is indeed due to the distinction between dominant and subordinate hands. Possible reasons for the difference between these results and those obtained with spatial-location stimuli are considered. Copyright © 2017 Elsevier B.V. All rights reserved.
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Bilbao, Ainhoa; Rieker, Claus; Cannella, Nazzareno; Parlato, Rosanna; Golda, Slawomir; Piechota, Marcin; Korostynski, Michal; Engblom, David; Przewlocki, Ryszard; Schütz, Günther; Spanagel, Rainer; Parkitna, Jan R.
2014-01-01
It is suggested that striatal cAMP responsive element binding protein (CREB) regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined the effects of a dominant-negative CREB protein variant expressed in dopamine receptor D1 (D1R) neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection of a BAC-derived transgene harboring the A-CREB sequence under the control of the D1R gene promoter. Compared to wild-type, drug-naïve mutants showed moderate alterations in gene expression, especially a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2. The behavioral responses to cocaine were elevated in mutant mice. Locomotor activity after acute treatment, psychomotor sensitization after intermittent drug injections and the conditioned locomotion after saline treatment were increased compared to wild-type littermates. Transgenic mice had significantly higher cocaine conditioned place preference, displayed normal extinction of the conditioned preference, but showed an augmented cocaine-seeking response following priming-induced reinstatement. This enhanced cocaine-seeking response was associated with increased levels of activity-regulated transcripts and prodynorphin. The primary reinforcing effects of cocaine were not altered in the mutant mice as they did not differ from wild-type in cocaine self-administration under a fixed ratio schedule at the training dose. Collectively, our data indicate that expression of a dominant-negative CREB variant exclusively in neurons expressing D1R is sufficient to recapitulate the previously reported behavioral phenotypes associated with virally expressed dominant-negative CREB. PMID:24966820
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Smith, Alistair J H; Potvin, Lynette R; Lilleskov, Erik A
2015-11-01
Ectomycorrhizal fungi (EcMF) typically colonize nursery seedlings, but nutritional and growth effects of these communities are only partly understood. To examine these effects, Picea glauca seedlings collected from a tree nursery naturally colonized by three dominant EcMF were divided between fertilized and unfertilized treatments. After one growing season seedlings were harvested, ectomycorrhizas identified using DNA sequencing, and seedlings analyzed for leaf nutrient concentration and content, and biomass parameters. EcMF community structure-nutrient interactions were tested using nonmetric multidimensional scaling (NMDS) combined with vector analysis of foliar nutrients and biomass. We identified three dominant species: Amphinema sp., Atheliaceae sp., and Thelephora terrestris. NMDS + envfit revealed significant community effects on seedling nutrition that differed with fertilization treatment. PERMANOVA and regression analyses uncovered significant species effects on host nutrient concentration, content, and stoichiometry. Amphinema sp. had a significant positive effect on phosphorus (P), calcium and zinc concentration, and P content; in contrast, T. terrestris had a negative effect on P concentration. In the unfertilized treatment, percent abundance of the Amphinema sp. negatively affected foliar nitrogen (N) concentration but not content, and reduced foliar N/P. In fertilized seedlings, Amphinema sp. was positively related to foliar concentrations of N, magnesium, and boron, and both concentration and content of manganese, and Atheliaceae sp. had a negative relationship with P content. Findings shed light on the community and species effects on seedling condition, revealing clear functional differences among dominants. The approach used should be scalable to explore function in more complex communities composed of unculturable EcMF.
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DeFelice, R.C.; Parrish, J.D.
2001-01-01
The invertebrate assemblages in sediments bordering exposed fringing reefs at Hanalei Bay, Kauai, Hawaii, were examined during July to September 1994. Densities of invertebrate animals larger than 0.5 mm in sediments of the bay ranged from counts of 10 260 m-2 in the fine carbonate sands of the central bay to 870 m-2 in the habitat dominated by terrigenous silt near the reef edge close to the Hanalei river mouth. Similar sediment types supported broadly similar infaunal communities. Within the primarily carbonate sediments, mean grain size and wave exposure appear to have an important influence on the community. Taxonomic richness, number of individuals, and diversity showed significant negative relationships with exposure to wave energy (as estimated by sand ripple wavelength). The number of individuals was also significantly correlated with mean grain size. Overall, polychaetes and small crustaceans were numerically dominant among the major taxonomic groups investigated. Macrophagous and microphagous polychaetes had significant, but opposite, associations with grain size. In addition, microphagous polychaetes were significantly negatively correlated with wave exposure. No habitat variable measured could explain the variation in percent composition of crustaceans or echinoderms in the sedimentary habitats. The percentage of gastropods in the community was significantly negatively correlated with grain size, grain-size standard deviation and exposure, and positively with percent organic carbon. Bivalves were significantly positively associated with depth and grain size. These strong relationships imply that, in Hanalei Bay, physical processes are especially important in influencing assemblage structure, and that community structure and composition vary continuously along environmental gradients.
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Pellegrini, Isabelle; Roche, Cathy; Quentien, Marie-Helene; Ferrand, Mireille; Gunz, Ginette; Thirion, Sylvie; Bagnis, Claude; Enjalbert, Alain; Franc, Jean-Louis
2006-12-01
The anterior pituitary-specific transcription factor Pit-1 was initially identified and cloned as a transactivator of the prolactin (PRL) and GH genes and later as a regulator of the TSHb gene. It was found to be a major developmental regulator, because natural Pit-1 gene mutations cause a dwarf phenotype in mice and cause combined pituitary hormone deficiency associated with pituitary hypoplasia in humans. To further investigate the growth-promoting effects of Pit-1, we used a strategy based on the use of dominant-negative Pit-1 mutants as an alternative means of inactivating endogenous Pit-1 functions. R271W, a Pit-1 mutant identified in one allele in patients with severe combined pituitary hormone deficiency, and Pit-1Delta1-123, a deletion mutant in which only the DNA binding domain of Pit-1 is conserved, were generated, and their ability to abolish the effects of the endogenous native Pit-1 in the differentiated proliferating somatolactotrope GH4C1 cell line was investigated. Enforced expression of the dominant-negative mutants in GH4C1 cells using recombinant lentiviral vectors decreased the levels of expression of known Pit-1 target genes such as PRL and GH, abolished the hormone release, and reduced cell viability by decreasing the growth rate and inducing apoptosis via a caspase-independent pathway. These results show for the first time that the growth-promoting effects of Pit-1 are at least partly due to the fact that this transcription factor prevents apoptotic cell death.
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Caveolin-1 is a negative regulator of caveolae-mediated endocytosis to the endoplasmic reticulum.
Le, Phuong U; Guay, Ginette; Altschuler, Yoram; Nabi, Ivan R
2002-02-01
Caveolae are flask-shaped invaginations at the plasma membrane that constitute a subclass of detergent-resistant membrane domains enriched in cholesterol and sphingolipids and that express caveolin, a caveolar coat protein. Autocrine motility factor receptor (AMF-R) is stably localized to caveolae, and the cholesterol extracting reagent, methyl-beta-cyclodextrin, inhibits its internalization to the endoplasmic reticulum implicating caveolae in this distinct receptor-mediated endocytic pathway. Curiously, the rate of methyl-beta-cyclodextrin-sensitive endocytosis of AMF-R to the endoplasmic reticulum is increased in ras- and abl-transformed NIH-3T3 cells that express significantly reduced levels of caveolin and few caveolae. Overexpression of the dynamin K44A dominant negative mutant via an adenovirus expression system induces caveolar invaginations sensitive to methyl-beta-cyclodextrin extraction in the transformed cells without increasing caveolin expression. Dynamin K44A expression further inhibits AMF-R-mediated endocytosis to the endoplasmic reticulum in untransformed and transformed NIH-3T3 cells. Adenoviral expression of caveolin-1 also induces caveolae in the transformed NIH-3T3 cells and reduces AMF-R-mediated endocytosis to the endoplasmic reticulum to levels observed in untransformed NIH-3T3 cells. Cholesterol-rich detergent-resistant membrane domains or glycolipid rafts therefore invaginate independently of caveolin-1 expression to form endocytosis-competent caveolar vesicles via rapid dynamin-dependent detachment from the plasma membrane. Caveolin-1 stabilizes the plasma membrane association of caveolae and thereby acts as a negative regulator of the caveolae-mediated endocytosis of AMF-R to the endoplasmic reticulum.
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Cornwall, Christopher E; Boyd, Philip W; McGraw, Christina M; Hepburn, Christopher D; Pilditch, Conrad A; Morris, Jaz N; Smith, Abigail M; Hurd, Catriona L
2014-01-01
Anthropogenically-modulated reductions in pH, termed ocean acidification, could pose a major threat to the physiological performance, stocks, and biodiversity of calcifiers and may devalue their ecosystem services. Recent debate has focussed on the need to develop approaches to arrest the potential negative impacts of ocean acidification on ecosystems dominated by calcareous organisms. In this study, we demonstrate the role of a discrete (i.e. diffusion) boundary layer (DBL), formed at the surface of some calcifying species under slow flows, in buffering them from the corrosive effects of low pH seawater. The coralline macroalga Arthrocardia corymbosa was grown in a multifactorial experiment with two mean pH levels (8.05 'ambient' and 7.65 a worst case 'ocean acidification' scenario projected for 2100), each with two levels of seawater flow (fast and slow, i.e. DBL thin or thick). Coralline algae grown under slow flows with thick DBLs (i.e., unstirred with regular replenishment of seawater to their surface) maintained net growth and calcification at pH 7.65 whereas those in higher flows with thin DBLs had net dissolution. Growth under ambient seawater pH (8.05) was not significantly different in thin and thick DBL treatments. No other measured diagnostic (recruit sizes and numbers, photosynthetic metrics, %C, %N, %MgCO3) responded to the effects of reduced seawater pH. Thus, flow conditions that promote the formation of thick DBLs, may enhance the subsistence of calcifiers by creating localised hydrodynamic conditions where metabolic activity ameliorates the negative impacts of ocean acidification.
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Considering ionic state in modeling sorption of pharmaceuticals to sewage sludge.
Rybacka, Aleksandra; Andersson, Patrik L
2016-12-01
Information on the partitioning of chemicals between particulate matter and water in sewage treatment plants (STPs) can be used to predict their subsequent environmental fate. However, this information can be challenging to acquire, especially for pharmaceuticals that are frequently present in ionized forms. This study investigated the relationship between the ionization state of active pharmaceutical ingredients (APIs) and their partitioning between water and sludge in STPs. We also investigated the underlying mechanisms of sludge sorption by using chemical descriptors based on ionized structures, and evaluated the usefulness of these descriptors in quantitative structure-property relationship (QSPR) modeling. K D values were collected for 110 APIs, which were classified as neutral, positive, or negative at pH 7. The models with the highest performance had the R 2 Y and Q 2 values of above 0.75 and 0.65, respectively. We found that the dominant intermolecular forces governing the interactions of neutral and positively charged APIs with sludge are hydrophobic, pi-pi, and dipole-dipole interactions, whereas the interactions of negatively charged APIs with sludge were mainly governed by covalent bonding as well as ion-ion, ion-dipole, and dipole-dipole interactions; hydrophobicity-driven interactions were rather unimportant. Including charge-related descriptors improved the models' performance by 5-10%, underlining the importance of electrostatic interactions. The use of descriptors calculated for ionized structures did not improve the model statistics for positive and negative APIs, but slightly increased model performance for neutral APIs. We attribute this to a better description of neutral zwitterions. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Discovery-dominance trade-off among widespread invasive ant species.
Bertelsmeier, Cleo; Avril, Amaury; Blight, Olivier; Jourdan, Hervé; Courchamp, Franck
2015-07-01
Ants are among the most problematic invasive species. They displace numerous native species, alter ecosystem processes, and can have negative impacts on agriculture and human health. In part, their success might stem from a departure from the discovery-dominance trade-off that can promote co-existence in native ant communities, that is, invasive ants are thought to be at the same time behaviorally dominant and faster discoverers of resources, compared to native species. However, it has not yet been tested whether similar asymmetries in behavioral dominance, exploration, and recruitment abilities also exist among invasive species. Here, we establish a dominance hierarchy among four of the most problematic invasive ants (Linepithema humile, Lasius neglectus, Wasmannia auropunctata, Pheidole megacephala) that may be able to arrive and establish in the same areas in the future. To assess behavioral dominance, we used confrontation experiments, testing the aggressiveness in individual and group interactions between all species pairs. In addition, to compare discovery efficiency, we tested the species' capacity to locate a food resource in a maze, and the capacity to recruit nestmates to exploit a food resource. The four species differed greatly in their capacity to discover resources and to recruit nestmates and to dominate the other species. Our results are consistent with a discovery-dominance trade-off. The species that showed the highest level of interspecific aggressiveness and dominance during dyadic interactions.
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The face of female dominance: Women with dominant faces have lower cortisol.
Gonzalez-Santoyo, Isaac; Wheatley, John R; Welling, Lisa L M; Cárdenas, Rodrigo A; Jimenez-Trejo, Francisco; Dawood, Khytam; Puts, David A
2015-05-01
The human face displays a wealth of information, including information about dominance and fecundity. Dominance and fecundity are also associated with lower concentrations of the stress hormone cortisol, suggesting that cortisol may negatively predict facial dominance and attractiveness. We digitally photographed 61 women's faces, had these images rated by men and women for dominance, attractiveness, and femininity, and explored relationships between these perceptions and women's salivary cortisol concentrations. In a first study, we found that women with more dominant-appearing, but not more attractive, faces had lower cortisol levels. These associations were not due to age, ethnicity, time since waking, testosterone, or its interaction with cortisol. In a second study, composite images of women with low cortisol were perceived as more dominant than those of women with high cortisol significantly more often than chance by two samples of viewers, with a similar but non-significant trend in a third sample. However, data on perceptions of attractiveness were mixed; low-cortisol images were viewed as more attractive by two samples of US viewers and as less attractive by a sample of Mexican viewers. Our results suggest that having a more dominant-appearing face may be associated with lower stress and hence lower cortisol in women, and provide further evidence regarding the information content of the human face. Copyright © 2015 Elsevier Inc. All rights reserved.
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X-linked dominant retinitis pigmentosa in an American family
DOE Office of Scientific and Technical Information (OSTI.GOV)
McGuire, R.E.; Daiger, S.P.; Blanton, S.H.
1994-09-01
Retinitis pigmentosa is a genetically heterogeneous disease with autosomal dominant (adRP), autosomal recessive and X-linked forms. At least 3 forms of X-linked retinitis pigmentosa have been reported: RP2 which maps to Xp11.4-p 11.23, RP3 which maps to Xp21.1 and RP6, which maps to Xp21.3-p21.1. The X-linked forms of retinitis pigmentosa are generally considered to be recessive as female carriers are not affected or are much less affected than males. Here we report a five generation American family with X-linked retinitis pigmentosa in which both males and females are significantly affected. The disease locus in this family appears to be distinctmore » from RP2 and RP3. The American family (UTAD054) presents with early-onset retinitis pigmentosa. The family appeared to fit an autosomal dominant pattern; however, linkage testing excluded all known adRP loci. Absence of male-to-male transmission in the pedigree suggested the possibility of X-linked dominant inheritance. Thus we tested six microsatellite markers that map to Xp (DXS987, DXS989, DXS993, DXS999, DXS1003 and DXS1110). Of these, DXS989 showed tight linkage with one allele (199) showing a 100% concordance with disease status. The odds favoring an X-linked dominant mode of inheritance in this family, versus autosomal dominant, are 10{sup 5}:1. In addition, recombinations for DXS999, and dXS1110, the two markers flanking DXS989, were observed in affected individuals. These data map the disease locus in this family to a 9 mb region on the X chromosome between Xp22.11 and Xp21.41. In addition, the recombinant individuals exclude close linkage to RP2 and RP3. The observance of high penetrance in females indicates that this family has X-linked dominant retinitis pigmentosa. We suggest that this mode of inheritance should be considered in other families with dominant retinitis pigmentosa but an absence of male-to-male transmission.« less
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Investigation of a Mercury-Argon Hot Cathode Discharge
NASA Astrophysics Data System (ADS)
Wamsley, Robert Charles
Classical absorption and laser induced fluorescence (LIF) experiments are used to investigate processes in the cathode region of a Hg-Ar hot cathode discharge. The absorption and LIF measurements are used to test the qualitative understanding and develop a quantitative model of a hot cathode discharge. The main contribution of this thesis is a model of the negative glow region that demonstrates the importance of Penning ionization to the ionization balance in the negative glow. We modeled the excited argon balance equation using a Monte Carlo simulation. In this simulation we used the trapped radiative decay rate of the resonance levels and the Penning ionization rate as the dominant loss terms in the balance equation. The simulated data is compared to and found to agree with absolute excited argon densities measured in a classical absorption experiment. We found the primary production rate per unit volume of excited Ar atoms in the simulation is sharply peaked near the cathode hot spot. We used the ion production rate from this simulation and a Green's function solution to the ambipolar diffusion equation to calculate the contribution of Penning ionization to the total ion density. We compared the results of this calculation to our experimental values of the Hg ^+ densities in the negative glow. We found that Penning ionization is an important and possibly the dominant ionization process in the negative glow.
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Pawełczyk, Tomasz; Kołodziej-Kowalska, Emilia; Pawełczyk, Agnieszka; Rabe-Jabłońska, Jolanta
2014-12-15
The effectiveness and predictors of response to electroconvulsive therapy (ECT) combined with antipsychotics (AP) in treatment-resistant schizophrenia patients with the dominance of negative symptoms (TRS-NS) have not been studied systematically so far. 29 patients aged 21-55 years diagnosed with TRS-NS underwent ECT combined with antipsychotics (ECT+AP). Prior to the ECT, the symptom profile and severity were evaluated using Positive and Negative Syndrome Scale (PANSS). Demographic and medical data was collected; ECT parameters and pharmacotherapy results were evaluated. After the combined ECT+AP therapy a significant decrease in symptom severity was found. A response to treatment was achieved by 60% of patients. The greatest reductions were obtained in general and positive PANSS subscale (median change: 11 and 7 pts.) and the smallest, but still significant, ones in negative symptoms subscale (median: 3.5 pts.). Patients who responded to ECT+AP demonstrated a significantly shorter duration of the current episode in comparison with patients who did not experience at least a 25% reduction in symptom severity (median: 4 vs. 8 months). A combination of ECT and antipsychotic therapy can provide a useful treatment option for patients with TRS-NS. The only significant predictor of response to treatment was a shorter duration of the current episode. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Miao, Ning; Liu, Shi-Rong; Shi, Zuo-Min; Yu, Hong; Liu, Xing-Liang
2009-06-01
Based on the investigation in a 4 hm2 Betula-Abies forest plot in sub-alpine area in West Sichuan of China, and by using point pattern analysis method in terms of O-ring statistics, the spatial patterns of dominant species Betula albo-sinensis and Abies faxoniana in different age classes in study area were analyzed, and the intra- and inter-species associations between these age classes were studied. B. albo-sinensis had a unimodal distribution of its DBH frequency, indicating a declining population, while A. faxoniana had a reverse J-shaped pattern, showing an increasing population. All the big trees of B. albo-sinensis and A. faxoniana were spatially in random at all scales, while the medium age and small trees were spatially clumped at small scales and tended to be randomly or evenly distributed with increasing spatial scale. The maximum aggregation degree decreased with increasing age class. Spatial association mainly occurred at small scales. A. faxoniana generally showed positive intra-specific association, while B. albo-sinensis generally showed negative intra-specific association. For the two populations, big and small trees had no significant spatial association, but middle age trees had negative spatial association. Negative inter-specific associations of the two populations were commonly found in different age classes. The larger the difference of age class, the stronger the negative inter-specific association.
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Cellular vacuolation induced by Clostridium perfringens epsilon-toxin.
Nagahama, Masahiro; Itohayashi, Yukari; Hara, Hideki; Higashihara, Masahiro; Fukatani, Yusuke; Takagishi, Teruhisa; Oda, Masataka; Kobayashi, Keiko; Nakagawa, Ichiro; Sakurai, Jun
2011-09-01
The epsilon-toxin of Clostridium perfringens forms a heptamer in the membranes of Madin-Darby canine kidney cells, leading to cell death. Here, we report that it caused the vacuolation of Madin-Darby canine kidney cells. The toxin induced vacuolation in a dose-dependent and time-dependent manner. The monomer of the toxin formed oligomers on lipid rafts in membranes of the cells. Methyl-β-cyclodextrin and poly(ethylene glycol) 4000 inhibited the vacuolation. Epsilon-toxin was internalized into the cells. Confocal microscopy revealed that the internalized toxin was transported from early endosomes (early endosome antigen 1 staining) to late endosomes and lysosomes (lysosomal-associated membrane protein 2 staining) and then distributed to the membranes of vacuoles. Furthermore, the vacuolation was inhibited by bafilomycin A1, a V-type ATPase inhibitor, and colchicine and nocodazole, microtubule-depolymerizing agents. The early endosomal marker green fluorescent protein-Rab5 and early endosome antigen 1 did not localize to vacuolar membranes. In contrast, the vacuolar membranes were specifically stained by the late endosomal and lysosomal marker green fluorescent protein-Rab7 and lysosomal-associated membrane protein 2. The vacuoles in the toxin-treated cells were stained with LysoTracker Red DND-99, a marker for late endosomes and lysosomes. A dominant negative mutant of Rab7 prevented the vacuolization, whereas a mutant form of Rab5 was less effective. These results demonstrate, for the first time, that: (a) oligomers of epsilon-toxin formed in lipid rafts are endocytosed; and (b) the vacuoles originating from late endosomes and lysosomes are formed by an oligomer of epsilon-toxin. © 2011 The Authors Journal compilation © 2011 FEBS.
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Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C
2018-01-01
Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is one of four residues that are important for receptor functional integrity, maintaining the binding pocket conformation and allowing rotation following ligand binding. Conclusion This novel dominant negative variant confirms the important role of R265 in EL3 in the functional integrity of P2Y12R, and suggests that pathologic heterodimer formation may underlie this family bleeding phenotype. © 2017 International Society on Thrombosis and Haemostasis.
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Salton, Gabrielle Dias; Laurino, Claudia Cilene Fernandes Correia; Mega, Nicolás Oliveira; Delgado-Cañedo, Andrés; Setterblad, Niclas; Carmagnat, Maryvonnick; Xavier, Ricardo Machado; Cirne-Lima, Elizabeth; Lenz, Guido; Henriques, João Antonio Pêgas; Laurino, Jomar Pereira
2017-08-03
Eukaryote initiation factor 2 subunit β (eIF2β) plays a crucial role in regulation protein synthesis, which mediates the interaction of eIF2 with mRNA. eIF2β contains evolutionarily conserved polylysine stretches in amino-terminal region and a zinc finger motif in the carboxy-terminus. The gene eIF2β was cloned under tetracycline transcription control and the polylysine stretches were deleted by site-directed mutagenesis (eIF2βΔ3K). The plasmid was transfected into HEK 293 TetR cells. These cells were analyzed for their proliferative and translation capacities as well as cell death rate. Experiments were performed using gene reporter assays, western blotting, flow cytometry, cell sorting, cell proliferation assays and confocal immunofluorescence. eIF2βΔ3K affected negatively the protein synthesis, cell proliferation and cell survival causing G2 cell cycle arrest and increased cell death, acting in a negative dominant manner against the native protein. Polylysine stretches are also essential for eIF2β translocated from the cytoplasm to the nucleus, accumulating in the nucleolus and eIF2βΔ3K did not make this translocation. eIF2β is involved in the protein synthesis process and should act in nuclear processes as well. eIF2βΔ3K reduces cell proliferation and causes cell death. Since translation control is essential for normal cell function and survival, the development of drugs or molecules that inhibit translation has become of great interest in the scenario of proliferative disorders. In conclusion, our results suggest the dominant negative eIF2βΔ3K as a therapeutic strategy for the treatment of proliferative disorders and that eIF2β polylysine stretch domains are promising targets for this.
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NASA Astrophysics Data System (ADS)
Hammer, Melanie S.; Martin, Randall V.; Li, Chi; Torres, Omar; Manning, Max; Boys, Brian L.
2018-06-01
Observations of aerosol scattering and absorption offer valuable information about aerosol composition. We apply a simulation of the Ultraviolet Aerosol Index (UVAI), a method of detecting aerosol absorption from satellite observations, to interpret UVAI values observed by the Ozone Monitoring Instrument (OMI) from 2005 to 2015 to understand global trends in aerosol composition. We conduct our simulation using the vector radiative transfer model VLIDORT with aerosol fields from the global chemical transport model GEOS-Chem. We examine the 2005-2015 trends in individual aerosol species from GEOS-Chem and apply these trends to the UVAI simulation to calculate the change in simulated UVAI due to the trends in individual aerosol species. We find that global trends in the UVAI are largely explained by trends in absorption by mineral dust, absorption by brown carbon, and scattering by secondary inorganic aerosol. Trends in absorption by mineral dust dominate the simulated UVAI trends over North Africa, the Middle East, East Asia, and Australia. The UVAI simulation resolves observed negative UVAI trends well over Australia, but underestimates positive UVAI trends over North Africa and Central Asia near the Aral Sea and underestimates negative UVAI trends over East Asia. We find evidence of an increasing dust source from the desiccating Aral Sea that may not be well represented by the current generation of models. Trends in absorption by brown carbon dominate the simulated UVAI trends over biomass burning regions. The UVAI simulation reproduces observed negative trends over central South America and West Africa, but underestimates observed UVAI trends over boreal forests. Trends in scattering by secondary inorganic aerosol dominate the simulated UVAI trends over the eastern United States and eastern India. The UVAI simulation slightly overestimates the observed positive UVAI trends over the eastern United States and underestimates the observed negative UVAI trends over India. Quantitative simulation of the OMI UVAI offers new insight into global trends in aerosol composition.
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Lido, Andria C V; França, Marcela M; Correa, Fernanda A; Otto, Aline P; Carvalho, Luciani R; Quedas, Elisangela P S; Nishi, Mirian Y; Mendonca, Berenice B; Arnhold, Ivo J P; Jorge, Alexander A L
2014-10-01
In most studies, the autosomal dominant (type II) form of isolated growth hormone deficiency (IGHD) has been more frequent than the autosomal recessive (type I) form. Our aim was to assess defects in the GH1 in short Brazilian children with different GH secretion status. We selected 135 children with postnatal short stature and classified according to the highest GH peak at stimulation tests in: severe IGHD (peak GH≤3.3 μg/L, n=38, all with normal pituitary magnetic resonance imaging); GH peak between 3.3 and 10 μg/L (n=76); and GH peak >10 μg/L (n=21). The entire coding region of GH1 was sequenced and complete GH1 deletions were assessed by Multiplex Ligation Dependent Probe Amplification and restriction enzyme digestion. Patients with severe IGHD had a higher frequency of consanguinity, were shorter, had lower levels of IGF-1 and IGFBP-3, and despite treatment with lower GH doses had a greater growth response than patients with GH peak ≥3.3 μg/L. Mutations were found only in patients with severe IGHD (GH peak<3.3 μg/L). Eight patients had autosomal recessive IGHD: Seven patients were homozygous for GH1 deletions and one patient was compound heterozygous for a GH1 deletion and the novel c.171+5G>C point mutation in intron 2, predicted to abolish the donor splice site. Only one patient, who was heterozygous for the c.291+1G>T mutation located at the universal donor splice site of intron 3 and predicts exon 3 skipping, had an autosomal dominant form. Analysis of GH1 in a cohort of Brazilian patients revealed that the autosomal recessive form of IGHD was more common than the dominant one, and both were found only in severe IGHD. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Mixotrophy in Heterocapsa rotundata: A Mechanism for Dominating the Winter Phytoplankton Community
NASA Astrophysics Data System (ADS)
Millette, N.; Pierson, J. J.; Aceves, A.; Stoecker, D.
2016-02-01
Heterocapsa rotundata is a dinoflagellate that forms large winter blooms in estuaries and coastal ecosystems. Past research has focused on the mechanisms necessary for these winter blooms to form but it is unknown why H. rotundata consistently forms these blooms. H. rotundata is a known mixotroph, and we conducted grazing experiments with a non-axenic culture of H. rotundata containing bacteria to test what environmental conditions increase H. rotundata's community grazing rate. We used microspheres to confirm that H. rotundata was grazing. We measured the change of bacterial abundance in control (without grazers) and experimental groups over 24 hours to estimate H. rotundata's community grazing rate on bacteria at different irradiance levels and ammonium concentrations. There was a significant interaction between the effect of ammonium concentration and irradiance levels. As irradiance levels decreased, the effect of ammonium concentrations on H. rotundata grazing rates became less pronounced. At lower irradiance levels H. rotundata grazing rates remained high, regardless of the ammonium concentration. Overall, changes in irradiance levels had a larger impact on H. rotundata grazing rates than changes in ammonium concentration. The findings will be discussed in light of ongoing lab and field research. The winter season is known for limiting light levels that most likely have a negative impact on phytoplankton growth rates. Heterocapsa rotundata has adapted to low light levels by increasing grazing on bacteria to consume enough carbon to maintain growth. Heterocapsa rotundata's response to low light levels is likely the mechanism that provides the competitive advantage to form winter blooms under the right conditions over other phytoplankton species.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Scott, D.A.; Sheffield, V.C.; Stone, E.M.
1995-10-01
Nonsyndromic deafness accounts for {approximately}70% of all genetically determined deafness. Several types of nonsyndromic deafness, with a variety of inheritance patterns, have been genetically linked, including dominant, recessive and X-linked forms. Two of these forms - DFNA3, a dominant form causing moderate to severe hearing loss, predominantly in the high frequencies, and DFNB1, a recessive form causing profound, prelingual, neurosensory deafness affecting all frequencies - have been linked to the same pericentromeric region of chromosome 13. This finding is equally compatible with (1) the existence two closely linked deafness genes, (2) different mutations within a single deafness gene, and (3)more » a single mutation in a single gene that behaves differently in different genetic backgrounds. 12 refs., 2 figs., 1 tab.« less
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The Nature of Stakeholder Satisfaction with Marketing Education
ERIC Educational Resources Information Center
Taylor, Steven A.; Judson, Kim
2014-01-01
The current article represents a cautionary tale in continuing emerging marketization practices as the dominant form of marketing with higher education. Specifically, a review of three important emerging literature streams (i.e., quality-of-life, service-dominant logic, and stakeholder orientation) all appear to support calls for moving beyond…
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Geneviève, D; Le Merrer, M; Feingold, J; Munnich, A; Maroteaux, P; Cormier-Daire, V
2008-04-15
Metatropic dysplasia (MD-OMIM: 156530 and 250600) is a rare chondrodysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis, first described in 1893. Up until now, 81 other patients have been reported. The phenotypic variability of MD has led to a classification based on radiological anomalies dividing into three different types: a lethal autosomal recessive form, an autosomal recessive non-lethal form and a non-lethal autosomal dominant form with less severe radiographs manifestations and a better clinical outcome. Here, we report on clinical and radiological features of 19 novel MD patients. We describe new radiological features, including precocious calcification of hyoid and cricoid cartilage, irregular and squared-off calcaneal bones and severe hypoplasia of the anterior portion of first cervical vertebrae. In addition, the observation of an overlap between the autosomal recessive non-lethal form and the non-lethal autosomal dominant form, the rarity of sibship recurrences and the observation of vertical transmissions of MD in the literature argue in favor of an autosomal dominant mode of inheritance for all MD types. This hypothesis is reinforced by the use of the statistical single ascertainment method that rejects the hypothesis of an autosomal recessive mode of inheritance responsible for MD. Therefore, we propose that recurrence in sibs is due to gonadal mosaicism. Copyright 2008 Wiley-Liss, Inc.
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Lewis, Kimberly L; Taubitz, Lauren E; Duke, Michael W; Steuer, Elizabeth L; Larson, Christine L
2015-12-01
Rumination has been shown to increase negative affect and is highly associated with increased duration of depressive episodes. Previous research has shown that enhanced elaborative processing of negative stimuli is often associated with depression and trait rumination. We hypothesized that engaging in rumination would result in sustained elaborative processing of negative information, as measured by late positive potential (LPP) asymmetry, regardless of depression. Participants were experimentally induced to engage in ruminative- or distraction-oriented thoughts and subsequently viewed negative, positive, and neutral images. Our results showed a very specific right-dominant frontal and parietal LPP to negative, but not neutral or positive, pictures in the rumination condition only that was not correlated with any measures of trait rumination or depression symptoms. This suggests that state rumination alone may lead to an enhanced, sustained processing of negative material that is typically associated with depression. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
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DOE Office of Scientific and Technical Information (OSTI.GOV)
McGuire, R.E.; Sullivan, L.S.; Daiger, S.P.
1995-07-01
Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneration, a variant form of retinitis pigmentosa. We used microsatellite markers to test for linkage to the disease locus and exluded all mapped autosomal loci. However, a marker from the short arm of the X chromosome, DXS989, showed 0% recombination to the disease locus, with a maximum lod (log-odds) score of 3.3. On the basis of this marker, themore » odds favoring X-linked dominant versus autosomal dominant inheritance are > 10{sup 5}:1. Haplotype analysis using an additional nine microsatellite markers places the disease locus in the Xp22.13-p22.11 region and excludes other X-linked disease loci causing retinal degeneration. The clinical expression of the retinal degeneration is consistent with X-linked dominant inheritance with milder, variable effects of Lyonization affecting expression in females. On the basis of these data we propose that this family has a novel form of dominant, X-linked cone-rod degeneration with the gene symbol {open_quotes}RP15{close_quotes}. 17 refs., 2 figs., 4 tabs.« less
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Lichens and microfungi in biocrusts: Structure and function now and in the future: Chapter 10
Belnap, Jayne; Lange, Otto L.; Dighton, J.; White, James F.
2017-01-01
Lichens and microfungi are an essential and often dominant part of biocrusts. About one fifth (19 %) of all known species of fungi are lichenized; that is, they form a stable symbiotic association with green algal or/and cyanobacterial photobionts that provide nutrients for the mycobiont (fungi). The vast majority of lichenized fungi belong to the Ascomycota, with 42% of all fungi in this group forming lichens (Kirk et al., 2001). About 85% of lichen-forming fungi are symbiotic with Chlorophyta (green algae, creating "chlorolichens), approximately 10% with Cyanophyta, (creating "cyanolichens"), and the remainder are associated simultaneously with both groups. About 40 genera of photobionts have been identified in lichens: 25 are green algae and 15 are cyanobacteria. The autotrophic lifestyle of lichens requires an exposure of the green thallus to light. Most lichens are long-lived organisms with high habitat specificity. They are especially ecologically successful in dryland areas where competition with phanerogamous vegetation is reduced. It is estimated that approximately 8% of the earth's terrestrial surface has lichens as its most dominant life-form (Ahmadjian 1995). One of their most important habitats are biocrusts, which lichens often dominate. In the present Chapter we concentrate on those widely distributed biocrusts in which free-living and lichenized fungi play a dominating role. We describe their community structure, analyze the special properties and functions of these organisms as key members of biocrusts, and then discuss the function of the fungi-rich biocrusts as components of larger ecosystems and landscapes (for details and specific literature, see Belnap and Lange 2003).