Preformed β-amyloid fibrils are destabilized by coenzyme Q10 in vitro

International Nuclear Information System (INIS)

Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu; Yamada, Masahito

2005-01-01

Inhibition of the formation of β-amyloid fibrils (fAβ), as well as the destabilization of preformed fAβ in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fAβ formation from Aβ and destabilize preformed fAβ in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q 10 (CoQ 10 ) on the formation, extension, and destabilization of fAβ at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ 10 with NDGA and Myr. CoQ 10 dose-dependently inhibited fAβ formation from amyloid β-peptide (Aβ), as well as their extension. Moreover, it destabilized preformed fAβs. The anti-amyloidogenic effects of CoQ 10 were slightly weaker than those of NDGA and Myr. CoQ 10 could be a key molecule for the development of therapeutics for AD

Submarine landslides triggered by destabilization of high-saturation hydrate anomalies

Science.gov (United States)

Handwerger, Alexander L.; Rempel, Alan W.; Skarbek, Rob M.

2017-07-01

Submarine landslides occur along continental margins at depths that often intersect the gas hydrate stability zone, prompting suggestions that slope stability may be affected by perturbations that arise from changes in hydrate stability. Here we develop a numerical model to identify the conditions under which the destabilization of hydrates results in slope failure. Specifically, we focus on high-saturation hydrate anomalies at fine-grained to coarse-grained stratigraphic boundaries that can transmit bridging stresses that decrease the effective stress at sediment contacts and disrupt normal sediment consolidation. We evaluate slope stability before and after hydrate destabilization. Hydrate anomalies act to significantly increase the overall slope stability due to large increases in effective cohesion. However, when hydrate anomalies destabilize there is a loss of cohesion and increase in effective stress that causes the sediment grains to rapidly consolidate and generate pore pressures that can either trigger immediate slope failure or weaken the surrounding sediment until the pore pressure diffuses away. In cases where failure does not occur, the sediment can remain weakened for months. In cases where failure does occur, we quantify landslide dynamics using a rate and state frictional model and find that landslides can display either slow or dynamic (i.e., catastrophic) motion depending on the rate-dependent properties, size of the stress perturbation, and the size of the slip patch relative to a critical nucleation length scale. Our results illustrate the fundamental mechanisms through which the destabilization of gas hydrates can pose a significant geohazard.

Electromagnetic waves destabilized by runaway electrons in near-critical electric fields

Energy Technology Data Exchange (ETDEWEB)

Komar, A.; Pokol, G. I. [Department of Nuclear Techniques, Budapest University of Technology and Economics, Association EURATOM, H-1111 Budapest (Hungary); Fueloep, T. [Department of Applied Physics, Nuclear Engineering, Chalmers University of Technology and Euratom-VR Association, Goeteborg (Sweden)

2013-01-15

Runaway electron distributions are strongly anisotropic in velocity space. This anisotropy is a source of free energy that may destabilize electromagnetic waves through a resonant interaction between the waves and the energetic electrons. In this work, we investigate the high-frequency electromagnetic waves that are destabilized by runaway electron beams when the electric field is close to the critical field for runaway acceleration. Using a runaway electron distribution appropriate for the near-critical case, we calculate the linear instability growth rate of these waves and conclude that the obliquely propagating whistler waves are most unstable. We show that the frequencies, wave numbers, and propagation angles of the most unstable waves depend strongly on the magnetic field. Taking into account collisional and convective damping of the waves, we determine the number density of runaways that is required to destabilize the waves and show its parametric dependences.

Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

Directory of Open Access Journals (Sweden)

Charlotte Rachael Flavell

2013-12-01

Full Text Available The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of a memory following it’s reactivation and/or extinction, and investigates the evidence that extinction may involve both new learning as well as a partial destabilization-induced erasure of the original memory trace.

Atherosclerotic Plaque Destabilization Mechanisms, Models, and Therapeutic Strategies

NARCIS (Netherlands)

Silvestre-Roig, Carlos; de Winther, Menno P.; Weber, Christian; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

2014-01-01

Understanding the pathophysiology of atherogenesis and the progression of atherosclerosis have been major goals of cardiovascular research during the previous decades. However, the complex molecular and cellular mechanisms underlying plaque destabilization remain largely obscure. Here, we review how

Energetic particle destabilization of shear Alfven waves in stellarators and tokamaks

International Nuclear Information System (INIS)

Spong, D.A.; Carreras, B.A.; Hedrick, C.L.; Leboeuf, J.N.; Weller, A.

1994-01-01

An important issue for ignited devices is the resonant destabilization of shear Alfven waves by energetic populations. These instabilities have been observed in a variety of toroidal plasma experiments in recent years, including: beam-destabilized toroidal Alfven instabilities (TAE) in low magnetic field tokamaks, ICRF destabilized TAE's in higher field tokamaks, and global Alfven instabilities (GAE) in low shear stellarators. In addition, excitation and study of these modes is a significant goal of the TFIR-DT program and a component of the ITER physics tasks. The authors have developed a gyrofluid model which includes the wave-particle resonances necessary to excite such instabilities. The TAE linear mode structure is calculated nonperturbatively, including many of the relevant damping mechanisms, such as: continuum damping, non-ideal effects (ion FLR and electron collisionality), and ion/electron Landau damping. This model has been applied to both linear and nonlinear regimes for a range of experimental cases using measured profiles

[Population pressure: a factor of political destabilization].

Science.gov (United States)

Tallon, F

1993-04-01

Political stability throughout the world appears to be greater in countries with slowly growing populations than in those with rapid growth. Population is not the only influence on political stability, however. The relationship between political stability and development is strong. The rich countries with the slowest growth are the most stable, while poor developing countries with rapid growth suffer from chronic instability. Demographic pressure and density are not the same thing and must be distinguished. A fragile environment like that of the Sahel will experience demographic pressure despite low density. Japan has a greater population density than Rwanda and little cultivable land, but the population has a high standard of living. demographic pressure is not comparable in Japan and Rwanda because Japan has slow population growth and stable democratic political institutions. The rate of growth seems to be a more important element in destabilization than density. Rapid growth creates enormous political tensions especially when profound ethnic divisions exist, and it complicates problems of government by encouraging rapid urbanization. The unbalanced age structures resulting from rapid growth hinder the satisfaction of employment, educational, and health care needs for the ever-increasing masses of young people. 49% of Rwanda's population is under 15 and 66% is under 25. Rwanda is already densely populated, with around 300 inhabitants/sq km, and its population is projected to double in 20 years. 95% of the population is dependent on agriculture, but by 1988 the average landholding per family was only 1.25 hectares and 58% of families did not grown sufficient food for household needs. Further reduction in the size of holdings or a growing landless population will have multiple consequences. Urban migration will inevitably increase, bringing with it all the problems so evident in other poor countries where the process is more advanced than in Rwanda. Chaotic

Slurry Erosion Behavior of Destabilized and Deep Cryogenically Treated Cr-Mn-Cu White Cast Irons

Directory of Open Access Journals (Sweden)

S. Gupta

2016-12-01

Full Text Available The effects of destabilization treatment and destabilization followed by cryogenic treatment have been evaluated on the microstructural evolution and sand-water slurry erosion behavior of Cr-Mn-Cu white cast irons. The phase transformations after the destabilization and cryotreatment have been characterized by bulk hardness measurement, optical and scanning electron microscopy, x-ray diffraction analysis. The static corrosion rate has been measured in tap water (with pH=7 and the erosion-corrosion behavior has been studied by slurry pot tester using sand-water slurry. The test results indicate that the cryogenic treatment has a significant effect in minimizing the as-cast retained austenite content and transforming into martensitic and bainitic matrix embedded with ultra-fine M7C3 alloy carbides. In contrast, by conventional destabilization treatment retained austenite in the matrix are not fully eliminated. The slurry erosive wear resistance has been compared with reference to destabilized and cryotreated high chromium iron samples which are commonly employed for such applications. The cryotreated Cr-Mn-Cu irons have exhibited a comparable erosive wear performance to those of high chromium irons. Higher hardness combined with improved corrosion resistance result in better slurry erosion resistance.

Destabilization of a peeling-ballooning mode by a toroidal rotation in tokamaks

International Nuclear Information System (INIS)

Aiba, N.; Hirota, M.; Tokuda, S.; Furukawa, M.

2009-01-01

Full text: From the viewpoint of the heat load on the divertor, Type-I edge localized mode (ELM) needs to be suppressed or the amplitude of this ELM needs to be reduced. In JT-60U, some experimental results showed that the ELM frequency depends on the toroidal rotation, and the rapid rotation in the counter direction of the plasma current changes from Type-I ELM to Grassy ELM, whose frequency is high and the amplitude is small. Recent experimental and theoretical/numerical studies in a static system have identified that both Type-I and Grassy ELMs are considered ideal magnetohydrodynamic (MHD) modes destabilizing near the plasma surface, called peeling-ballooning modes. To investigate the mechanism of the change of ELM frequency by a toroidal rotation, theoretical and numerical analyses are important for understanding the toroidal rotation effects on the peeling-ballooning mode. Previous works about the toroidal rotation effect on the edge MHD stability have illustrated that the toroidal rotation with shear can destabilize low/intermediate-n (<50) modes but can stabilize high-n modes, where n is the toroidal mode number. The stabilization of the high-n mode can be understood qualitatively in analogy with the infinite-n ballooning mode case. However, the destabilizing mechanism of the low/intermediate-n mode is not still clarified, and to understand the stability property related to ELM suppression/mitigation, it is important to clarify this destabilizing mechanism. In this paper, we investigate numerically the destabilizing effect of a toroidal rotation on the peeling-ballooning mode with a newly developed code MINERVA, which solves the Frieman-Rotenberg equation. Particularly, we pay attention to the effect of the centrifuged force on not only equilibrium but also change of equation of motion. (author)

Allosteric Mutant IDH1 Inhibitors Reveal Mechanisms for IDH1 Mutant and Isoform Selectivity

Energy Technology Data Exchange (ETDEWEB)

Xie, Xiaoling; Baird, Daniel; Bowen, Kimberly; Capka, Vladimir; Chen, Jinyun; Chenail, Gregg; Cho, YoungShin; Dooley, Julia; Farsidjani, Ali; Fortin, Pascal; Kohls, Darcy; Kulathila, Raviraj; Lin, Fallon; McKay, Daniel; Rodrigues, Lindsey; Sage, David; Touré, B. Barry; van der Plas, Simon; Wright, Kirk; Xu, Ming; Yin, Hong; Levell, Julian; Pagliarini, Raymond A. (Novartis)

2017-03-01

Oncogenic IDH1 and IDH2 mutations contribute to cancer via production of R-2-hydroxyglutarate (2-HG). Here, we characterize two structurally distinct mutant- and isoform-selective IDH1 inhibitors that inhibit 2-HG production. Both bind to an allosteric pocket on IDH1, yet shape it differently, highlighting the plasticity of this site. Oncogenic IDH1R132H mutation destabilizes an IDH1 “regulatory segment,” which otherwise restricts compound access to the allosteric pocket. Regulatory segment destabilization in wild-type IDH1 promotes inhibitor binding, suggesting that destabilization is critical for mutant selectivity. We also report crystal structures of oncogenic IDH2 mutant isoforms, highlighting the fact that the analogous segment of IDH2 is not similarly destabilized. This intrinsic stability of IDH2 may contribute to observed inhibitor IDH1 isoform selectivity. Moreover, discrete residues in the IDH1 allosteric pocket that differ from IDH2 may also guide IDH1 isoform selectivity. These data provide a deeper understanding of how IDH1 inhibitors achieve mutant and isoform selectivity.

Positive Feedback Investment Strategies and Destabilizing Rational Speculation

OpenAIRE

J. Bradford De Long; Andrei Shleifer; Lawrence H. Summers; Robert J. Waldmann

1989-01-01

Analyses of the role of rational speculators in financial markets usually presume that such investors dampen price fluctuations by trading against liquidity or noise traders. This conclusion does not necessarily hold when noise traders follow positive-feedback investment strategies buy when prices rise and sell when prices fall. In such cases, it may pay rational speculators to try to jump on the bandwagon early and to purchase ahead of noise trader demand. If rational speculators' attempts t...

A density functional study of backbone structures of polydiacetylene: destabilization of butatriene structure

International Nuclear Information System (INIS)

Katagiri, Hideki; Shimoi, Yukihiro; Abe, Shuji

2004-01-01

Backbone structures of polydiacetylene are studied with first-principles electronic structure method using plane-waves within generalized gradient approximation (GGA) of density functional theory. In spin-restricted calculations a coarse k-point sampling gives a potential energy curve with two local minima corresponding to acetylene and butatriene structures. However, the potential barrier between the two structures rapidly decreases with increasing number of k-points, which results in destabilization of the butatriene structure. Spin polarization effects also destabilize the butatriene structure, inducing atom-centered spin-density-wave state. These potential energies were compared with those obtained by Hartree-Fock, density functional within local density approximation (LDA) and GGA, and hybrid density functional methods using a gaussian basis set. The comparison shows that the density functional methods within LDA and GGA favor the destabilization of the butatriene structure in contrast to the Hartree-Fock method

Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

OpenAIRE

Flavell, Charlotte R.; Lambert, Elliot A.; Winters, Boyer D.; Bredy, Timothy W.

2013-01-01

The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session) can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of...

Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

Science.gov (United States)

Guo, Muyi; Cai, Yan; Yao, Xinke; Li, Zhiyong

2018-08-07

Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum. Three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemicals (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase) are involved in the plaque progression model, and described by the reaction-diffusion partial differential equations. The hemodynamic calculation of the microcirculation on the generated microvessel network is carried out by coupling the intravascular, interstitial and transvascular flow. The plasma concentration in the interstitial domain is defined as the description of IPH area according to the diffusion and convection with the interstitial fluid flow, as well as the extravascular movement across the leaky vessel wall. The simulation results demonstrate a series of pathophysiological phenomena during the vulnerable progression of an atherosclerotic plaque, including the expanding necrotic core, the exacerbated inflammation, the high microvessel density (MVD) region at the shoulder areas, the transvascular flow through the capillary wall and the IPH. The important role of IPH in the plaque destabilization is evidenced by simulations with varied model parameters. It is found that the IPH can significantly speed up the plaque vulnerability by increasing necrotic core and thinning fibrous cap. In addition, the decreased MVD and vessel permeability may slow down the process of

Patterns of positive selection in six Mammalian genomes

DEFF Research Database (Denmark)

Kosiol, Carolin; Vinar, Tomás; da Fonseca, Rute R

2008-01-01

Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small...... several new lineage- and clade-specific tests to be applied. Of approximately 16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR... showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity...

Reference satellite selection method for GNSS high-precision relative positioning

Directory of Open Access Journals (Sweden)

Xiao Gao

2017-03-01

Full Text Available Selecting the optimal reference satellite is an important component of high-precision relative positioning because the reference satellite directly influences the strength of the normal equation. The reference satellite selection methods based on elevation and positional dilution of precision (PDOP value were compared. Results show that all the above methods cannot select the optimal reference satellite. We introduce condition number of the design matrix in the reference satellite selection method to improve structure of the normal equation, because condition number can indicate the ill condition of the normal equation. The experimental results show that the new method can improve positioning accuracy and reliability in precise relative positioning.

DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences

Directory of Open Access Journals (Sweden)

Gaëlle Lenglet

2010-01-01

Full Text Available DNA targeting drugs represent a large proportion of the actual anticancer drug pharmacopeia, both in terms of drug brands and prescription volumes. Small DNA-interacting molecules share the ability of certain proteins to change the DNA helix's overall organization and geometrical orientation via tilt, roll, twist, slip, and flip effects. In this ocean of DNA-interacting compounds, most stabilize both DNA strands and very few display helix-destabilizing properties. These types of DNA-destabilizing effect are observed with certain mono- or bis-intercalators and DNA alkylating agents (some of which have been or are being developed as cancer drugs. The formation of locally destabilized DNA portions could interfere with protein/DNA recognition and potentially affect several crucial cellular processes, such as DNA repair, replication, and transcription. The present paper describes the molecular basis of DNA destabilization, the cellular impact on protein recognition, and DNA repair processes and the latter's relationships with antitumour efficacy.

Selective control of attention supports the positivity effect in aging.

Science.gov (United States)

Sasse, Laura K; Gamer, Matthias; Büchel, Christian; Brassen, Stefanie

2014-01-01

There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging.

Evidence for Very Recent Positive Selection in Mongolians.

Science.gov (United States)

Nakayama, Kazuhiro; Ohashi, Jun; Watanabe, Kazuhisa; Munkhtulga, Lkagvasuren; Iwamoto, Sadahiko

2017-08-01

Mongols, the founders of the largest continental empire in history, successfully adapted to the harsh environments of Inner Asia through nomadic pastoralism. Considerable interest exists in ascertaining whether genetic adaptation also contributed to the Mongols' success, and dissecting the genome diversity of present-day populations in Mongolia can help address this question. To this end, we determined the genotypes of nearly 2.4 million single nucleotide polymorphisms (SNPs) of 96 unrelated Mongolian individuals in Ulaanbaatar city, and performed genome-wide scans for population-specific positive selection. We discovered signatures of Mongolian-specific positive selection at the chromosomal region 3p12.1, in which hits in genome-wide association studies were reported for medical and biological traits related to energy metabolism and reproduction. The top SNP, rs117799927, showed a distinctive geographic distribution: the frequency of the derived allele, rs117799927 G, was extremely low among worldwide populations (0.005) but exceptionally high in Mongolians (0.247). Approximate Bayesian computation-based age estimation showed that the rs117799927 G allele emerged or positive selection began to operate 50 generations before the present, near the age of the climate anomaly named Late Antique Little Ice Age. Furthermore, rs117799927 showed significant associations with multiple adiposity-related traits in Mongolians and allelic difference in enhancer activity in cells of adipocyte lineage, suggesting that positive selection at 3p12.1 might be related to adaptation in the energy metabolism system. These findings provide novel evidence for a very recent positive-selection event in Homo sapiens and offer insights into the roles of genes in 3p12.1 in the adaptive evolution of our species. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Directional Positive Selection on an Allele of Arbitrary Dominance

OpenAIRE

Teshima, Kosuke M.; Przeworski, Molly

2006-01-01

Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.

Selective control of attention supports the positivity effect in aging.

Directory of Open Access Journals (Sweden)

Laura K Sasse

Full Text Available There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging.

THE ESTIMATION OF HUMAN-OPERATOR CYBERNETIC ABILITIES DURING THE IMPACT OF DESTABILIZING FACTORS OF EXTERNAL ENVIRONMENT

Directory of Open Access Journals (Sweden)

Sergii T. Polishchuk

2009-04-01

Full Text Available  The method of estimation of human-operator cybernetics abilities during of the impacting of destabilizing factors of external environment is suggested. It was proved that up-to-date biomedical approach for periodical health examination of pilots in civil aviation isn’t guarantees theirs cybernetics abilities in cases of influence of destabilizing factors.

The effects of cognitive reappraisal following retrieval-procedures designed to destabilize alcohol memories in high-risk drinkers.

Science.gov (United States)

Hon, Tiffany; Das, Ravi K; Kamboj, Sunjeev K

2016-03-01

Addiction is a disorder of motivational learning and memory. Maladaptive motivational memories linking drug-associated stimuli to drug seeking are formed over hundreds of reinforcement trials and accompanied by aberrant neuroadaptation in the mesocorticolimbic reward system. Such memories are resistant to extinction. However, the discovery of retrieval-dependent memory plasticity has opened up the possibility of permanent modification of established (long-term) memories during 'reconsolidation'. Here, we investigate whether reappraisal of maladaptive alcohol cognitions performed after procedures designed to destabilize alcohol memory networks affected subsequent alcohol memory, craving, drinking and attentional bias. Forty-seven at-risk drinkers attended two sessions. On the first lab session, participants underwent one of two prediction error-generating procedures in which outcome expectancies were violated while retrieving alcohol memories (omission and value prediction error groups). Participants in a control group retrieved non-alcohol memories. Participants then reappraised personally relevant maladaptive alcohol memories and completed measures of reappraisal recall, alcohol verbal fluency and craving. Seven days later, they repeated these measures along with attentional bias assessment. Omission prediction error (being unexpectedly prevented from drinking beer), but not a value prediction error (drinking unexpectedly bitter-tasting beer) or control procedure (drinking unexpectedly bitter orange juice), was associated with significant reductions in verbal fluency for positive alcohol-related words. No other statistically robust outcomes were detected. This study provides partial preliminary support for the idea that a common psychotherapeutic strategy used in the context of putative memory retrieval-destabilization can alter accessibility of alcohol semantic networks. Further research delineating the necessary and sufficient requirements for producing

E-cadherin destabilization accounts for the pathogenicity of missense mutations in hereditary diffuse gastric cancer.

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Joana Simões-Correia

Full Text Available E-cadherin is critical for the maintenance of tissue architecture due to its role in cell-cell adhesion. E-cadherin mutations are the genetic cause of Hereditary Diffuse Gastric Cancer (HDGC and missense mutations represent a clinical burden, due to the uncertainty of their pathogenic role. In vitro and in vivo, most mutations lead to loss-of-function, although the causal factor is unknown for the majority. We hypothesized that destabilization could account for the pathogenicity of E-cadherin missense mutations in HDGC, and tested our hypothesis using in silico and in vitro tools. FoldX algorithm was used to calculate the impact of each mutation in E-cadherin native-state stability, and the analysis was complemented with evolutionary conservation, by SIFT. Interestingly, HDGC patients harbouring germline E-cadherin destabilizing mutants present a younger age at diagnosis or death, suggesting that the loss of native-state stability of E-cadherin accounts for the disease phenotype. To elucidate the biological relevance of E-cadherin destabilization in HDGC, we investigated a group of newly identified HDGC-associated mutations (E185V, S232C and L583R, of which L583R is predicted to be destabilizing. We show that this mutation is not functional in vitro, exhibits shorter half-life and is unable to mature, due to premature proteasome-dependent degradation, a phenotype reverted by stabilization with the artificial mutation L583I (structurally tolerated. Herein we report E-cadherin structural models suitable to predict the impact of the majority of cancer-associated missense mutations and we show that E-cadherin destabilization leads to loss-of-function in vitro and increased pathogenicity in vivo.

Positive selection on the killer whale mitogenome

DEFF Research Database (Denmark)

Foote, Andrew David; Morin, Phillip A.; Durban, John W.

2011-01-01

Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The coding genes of the mitochondrial DNA may therefore evolve under selection owing to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a global distribution and occupies a range of ecological niches....... It is therefore a suitable organism for testing this hypothesis. We compared a global dataset of the complete mitochondrial genomes of 139 individuals for amino acid changes that were associated with radical physico-chemical property changes and were influenced by positive selection. Two such selected non...

Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze

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Kim Ryang

2011-02-01

Full Text Available Abstract Background Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory. Results We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1 and L-type voltage gated calcium channels (LVGCCs in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis. Conclusions Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

SEASONAL VARIATION IN LYSOSOMAL DESTABILIZATION IN OYSTERS, CRASSOSTREA VIRGINICA. (R826201)

Science.gov (United States)

Lysosomal destabilization assays have been used as valuable biomarkers of pollutant exposures in a variety of bivalve and fish species. The responses of oysters, Crassostrea virginica, deployed at and native to various reference and degraded sites were evaluated for lys...

Destabilization of the electron Bernstein modes by runaway electrons

International Nuclear Information System (INIS)

Hitchcock, D.A.; Mahajan, S.M.

1982-01-01

It is shown that the electromagnetic finite k/sub parallel/ electron Bernstein mode can be destabilized by the runaway electron distribution which results from the quasilinear action of the magnetized plasma oscillation. This mechanism is shown to yield growth rates of the order of 10 8 sec -1 and is suggested as a mechanism for the enchanced cyclotron harmonic emission in the presence of runaway electrons

Core localized toroidal Alfven eigenmodes destabilized by energetic ions in the CHS heliotron/torsatron

International Nuclear Information System (INIS)

Takechi, M.; Matsunaga, G.; Takagi, S.

1999-09-01

Toroidal Alfven eigenmodes (TAE) destabilized by the pressure gradient of energetic alpha particles may expel the alpha particles before thermalization. TAE is important for tokamaks, and for helical systems (stellarators) as well. In CHS (compact helical system) TAE localized in the plasma core are destabilized when the plasma current is induced by co-injection of neutral beams. The observed TAE exhibits a ballooning nature. The internal structure of TAE was measured with a soft X-ray detector. The soft X-ray fluctuations level for TAE is too low to obtain the radial profiles of fluctuation intensities. (Tanaka, M.)

A scan for positively selected genes in the genomes of humans and chimpanzees.

Directory of Open Access Journals (Sweden)

Rasmus Nielsen

2005-06-01

Full Text Available Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

A map of recent positive selection in the human genome.

Directory of Open Access Journals (Sweden)

Benjamin F Voight

2006-03-01

Full Text Available The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest approximately 250 signals of recent selection in each population.

Stabilization and destabilization effects of the electric field on stochastic precipitate pattern

NARCIS (Netherlands)

Lagzi, István; Izsak, F.

2004-01-01

Stabilization and destabilization effects of an applied electric field on the Liesegang pattern formation in low concentration gradient were studied with numerical model simulations. In the absence of an electric field pattern formation exhibits increasingly stochastic behaviour as the initial

Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers

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Hsieh Hsing-Pang

2009-07-01

Full Text Available Abstract Background Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA damaging agent and paclitaxel (microtubule stabilizer in cancers. However, survivin-induced resistance to microtubule de-stabilizers such as Vinca alkaloids and Combretastatin A-4 (CA-4-related compounds were seldom demonstrated in the past. Furthermore, the question remains as to whether survivin plays a dominant role in processing cytokinesis or inhibiting caspases activity in cells treated with anti-mitotic compounds. The purpose of this study is to evaluate the effect of survivin on the resistance and susceptibility of human cancer cells to microtubule de-stabilizer-induced cell death. Results BPR0L075 is a CA-4 analog that induces microtubule de-polymerization and subsequent caspase-dependent apoptosis. To study the relationship between the expression of survivin and the resistance to microtubule de-stabilizers, a KB-derived BPR0L075-resistant cancer cell line, KB-L30, was generated for this study. Here, we found that survivin was over-expressed in the KB-L30 cells. Down-regulation of survivin by siRNA induced hyper-sensitivity to BPR0L075 in KB cells and partially re-stored sensitivity to BPR0L075 in KB-L30 cells. Western blot analysis revealed that down-regulation of survivin induced microtubule de-stabilization in both KB and KB-L30 cells. However, the same treatment did not enhance the down-stream caspase-3/-7 activities in BPR0L075-treated KB cells. Translocation of a caspase-independent apoptosis-related molecule, apoptosis-inducing factor (AIF, from cytoplasm to the nucleus was observed in survivin-targeted KB cells under BPR0L075 treatment. Conclusion In this study, survivin plays an important role in the

Photo-triggered destabilization of nanoscopic vehicles by dihydroindolizine for enhanced anticancer drug delivery in cervical carcinoma.

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Singh, Priya; Choudhury, Susobhan; Kulanthaivel, Senthilguru; Bagchi, Damayanti; Banerjee, Indranil; Ahmed, Saleh A; Pal, Samir Kumar

2018-02-01

The efficacy and toxicity of drugs depend not only on their potency but also on their ability to reach the target sites in preference to non-target sites. In this regards destabilization of delivery vehicles induced by light can be an effective strategy for enhancing drug delivery with spatial and temporal control. Herein we demonstrate that the photoinduced isomerization from closed (hydrophobic) to open isomeric form (hydrophilic) of a novel DHI encapsulated in liposome leads to potential light-controlled drug delivery vehicles. We have used steady state and picosecond resolved dynamics of a drug 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) incorporated in liposome to monitor the efficacy of destabilization of liposome in absence and presence UVA irradiation. Steady state and picosecond resolved polarization gated spectroscopy including the well-known strategy of solvation dynamics and Förster resonance energy transfer; reveal the possible mechanism out of various phenomena involved in destabilization of liposome. We have also investigated the therapeutic efficacy of doxorubicin (DOX) delivery from liposome to cervical cancer cell line HeLa. The FACS, confocal fluorescence microscopic and MTT assay studies reveal an enhanced cellular uptake of DOX leading to significant reduction in cell viability (∼40%) of HeLa followed by photoresponsive destabilization of liposome. Our studies successfully demonstrate that these DHI encapsulated liposomes have potential application as a smart photosensitive drug delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

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Rutault, K; Hazzalin, C A; Mahadevan, L C

2001-03-02

Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

Positive Selection and Centrality in the Yeast and Fly Protein-Protein Interaction Networks

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Sandip Chakraborty

2016-01-01

Full Text Available Proteins within a molecular network are expected to be subject to different selective pressures depending on their relative hierarchical positions. However, it is not obvious what genes within a network should be more likely to evolve under positive selection. On one hand, only mutations at genes with a relatively high degree of control over adaptive phenotypes (such as those encoding highly connected proteins are expected to be “seen” by natural selection. On the other hand, a high degree of pleiotropy at these genes is expected to hinder adaptation. Previous analyses of the human protein-protein interaction network have shown that genes under long-term, recurrent positive selection (as inferred from interspecific comparisons tend to act at the periphery of the network. It is unknown, however, whether these trends apply to other organisms. Here, we show that long-term positive selection has preferentially targeted the periphery of the yeast interactome. Conversely, in flies, genes under positive selection encode significantly more connected and central proteins. These observations are not due to covariation of genes’ adaptability and centrality with confounding factors. Therefore, the distribution of proteins encoded by genes under recurrent positive selection across protein-protein interaction networks varies from one species to another.

The signature of positive selection at randomly chosen loci.

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Przeworski, Molly

2002-03-01

In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequency alleles drift to fixation and no longer contribute to polymorphism, while linkage disequilibrium is broken down by recombination. As a result, loci chosen without independent evidence of recent selection are not expected to exhibit either of these features, even if they have been affected by numerous sweeps in their genealogical history. How then can we explain the patterns in the data? One possibility is population structure, with unequal sampling from different subpopulations. Alternatively, positive selection may not operate as is commonly modeled. In particular, the rate of fixation of advantageous mutations may have increased in the recent past.

Insight into microtubule destabilization mechanism of 3,4,5-trimethoxyphenyl indanone derivatives using molecular dynamics simulation and conformational modes analysis

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Tripathi, Shubhandra; Srivastava, Gaurava; Singh, Aastha; Prakasham, A. P.; Negi, Arvind S.; Sharma, Ashok

2018-03-01

Colchicine site inhibitors are microtubule destabilizers having promising role in cancer therapeutics. In the current study, four such indanone derivatives (t1, t9, t14 and t17) with 3,4,5-trimethoxyphenyl fragment (ring A) and showing significant microtubule destabilization property have been explored. The interaction mechanism and conformational modes triggered by binding of these indanone derivatives and combretastatin at colchicine binding site (CBS) of αβ-tubulin dimer were studied using molecular dynamics (MD) simulation, principle component analysis and free energy landscape analysis. In the MD results, t1 showed binding similar to colchicine interacting in the deep hydrophobic core at the CBS. While t9, t14 and t17 showed binding conformation similar to combretastatin, with ring A superficially binding at the CBS. Results demonstrated that ring A played a vital role in binding via hydrophobic interactions and got anchored between the S8 and S9 sheets, H8 helix and T7 loop at the CBS. Conformational modes study revealed that twisting and bending conformational motions (as found in the apo system) were nearly absent in the ligand bound systems. Absence of twisting motion might causes loss of lateral contacts in microtubule, thus promoting microtubule destabilization. This study provides detailed account of microtubule destabilization mechanism by indanone ligands and combretastatin, and would be helpful for designing microtubule destabilizers with higher activity.

Positive selection within the Schizophrenia-associated GABA(A receptor beta(2 gene.

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Wing-Sze Lo

Full Text Available The gamma-aminobutyric acid type-A (GABA(A receptor plays a major role in inhibitory neurotransmissions. Intronic SNPs and haplotypes in GABRB2, the gene for GABA(A receptor beta(2 subunit, are associated with schizophrenia and correlated with the expression of two alternatively spliced beta(2 isoforms. In the present study, using chimpanzee as an ancestral reference, high frequencies were observed for the derived (D alleles of the four SNPs rs6556547, rs187269, rs1816071 and rs1816072 in GABRB2, suggesting the occurrence of positive selection for these derived alleles. Coalescence-based simulation showed that the population frequency spectra and the frequencies of H56, the haplotype having all four D alleles, significantly deviated from neutral-evolution expectation in various demographic models. Haplotypes containing the derived allele of rs1816072 displayed significantly less diversity compared to haplotypes containing its ancestral allele, further supporting positive selection. The variations in DD-genotype frequencies in five human populations provided a snapshot of the evolutionary history, which suggested that the positive selections of the D alleles are recent and likely ongoing. The divergence between the DD-genotype profiles of schizophrenic and control samples pointed to the schizophrenia-relevance of positive selections, with the schizophrenic samples showing weakened selections compared to the controls. These DD-genotypes were previously found to increase the expression of beta(2, especially its long isoform. Electrophysiological analysis showed that this long beta(2 isoform favored by the positive selections is more sensitive than the short isoform to the inhibition of GABA(A receptor function by energy depletion. These findings represent the first demonstration of positive selection in a schizophrenia-associated gene.

Is the posterior cruciate ligament destabilized after the tibial cut in a cruciate retaining total knee replacement? An anatomical study.

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Liabaud, Barthelemy; Patrick, David A; Geller, Jeffrey A

2013-12-01

Cruciate retaining total knee replacement has been shown to effectively improve pain and quality of life. Successful outcomes depend on many factors, including the maintenance of a competent posterior cruciate ligament. This study sought to anatomically analyze the percentage of PCL injured during a full transverse, tibial cut, thus altering normal function. One hundred and thirty five consecutive knee MRIs taken from 2006 to 2011 were selected from a single surgeon's database for this study. Only subjects with non-arthritic knees were considered for this study; the lack of degenerative joint disease (DJD) was confirmed via a radiological report. The optimal view of the PCL's tibial attachment was observed using the sagittal view of the knee, with a T1 signal. One hundred and twenty two usable images were viewed electronically, and measurements were made using the standardized transverse cut implant guidelines. The percentage of PCL remaining following the cut was categorized into five different groups: 0% (no PCL undermined), 1-49%, 50-74%, 75-99% and 100% (PCL undermined entirely). Overall only 9.0% (n=11) would have not endured any damage to the PCL with a transverse tibial saw cut, while 79.6% (n=98) would have had 50% or more of the PCL undermined. Of the 98 patients with more than 50% resected, 52.1% (n=51 patients) presented complete destabilization of the PCL. The percentage of PCL destabilized was not significant across age groups (p=0.280), gender (p=0.586), or operative side (p=0.460). Independent of age, gender, and operative side, a majority of PCLs are more than 50% destabilized following the standard transverse tibial cut. II. Copyright © 2013 Elsevier B.V. All rights reserved.

Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

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Yue Huang

Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

NARCIS (Netherlands)

Bot, M.; , van, Berkel T.J.C.

2013-01-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by

Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

LENUS (Irish Health Repository)

Li, Wenfu

2011-04-21

Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

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Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

2016-09-11

A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Position paper - peer review and design verification of selected activities

International Nuclear Information System (INIS)

Stine, M.D.

1994-09-01

Position Paper to develop and document a position on the performance of independent peer reviews on selected design and analysis components of the Title I (preliminary) and Title II (detailed) design phases of the Multi-Function Waste Tank Facility project

How to Make a Dolphin: Molecular Signature of Positive Selection in Cetacean Genome.

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Mariana F Nery

Full Text Available Cetaceans are unique in being the only mammals completely adapted to an aquatic environment. This adaptation has required complex changes and sometimes a complete restructuring of physiology, behavior and morphology. Identifying genes that have been subjected to selection pressure during cetacean evolution would greatly enhance our knowledge of the ways in which genetic variation in this mammalian order has been shaped by natural selection. Here, we performed a genome-wide scan for positive selection in the dolphin lineage. We employed models of codon substitution that account for variation of selective pressure over branches on the tree and across sites in a sequence. We analyzed 7,859 nuclear-coding ortholog genes and using a series of likelihood ratio tests (LRTs, we identified 376 genes (4.8% with molecular signatures of positive selection in the dolphin lineage. We used the cow as the sister group and compared estimates of selection in the cetacean genome to this using the same methods. This allowed us to define which genes have been exclusively under positive selection in the dolphin lineage. The enrichment analysis found that the identified positively selected genes are significantly over-represented for three exclusive functional categories only in the dolphin lineage: segment specification, mesoderm development and system development. Of particular interest for cetacean adaptation to an aquatic life are the following GeneOntology targets under positive selection: genes related to kidney, heart, lung, eye, ear and nervous system development.

Medical expert system for assessment of coronary heart disease destabilization based on the analysis of the level of soluble vascular adhesion molecules

Science.gov (United States)

Serkova, Valentina K.; Pavlov, Sergey V.; Romanava, Valentina A.; Monastyrskiy, Yuriy I.; Ziepko, Sergey M.; Kuzminova, Nanaliya V.; Wójcik, Waldemar; DzierŻak, RóŻa; Kalizhanova, Aliya; Kashaganova, Gulzhan

2017-08-01

Theoretical and practical substantiation of the possibility of the using the level of soluble vascular adhesion molecules (sVCAM) is performed. Expert system for the assessment of coronary heart disease (CHD) destabilization on the base of the analysis of soluble vascular adhesion molecules level is developed. Correlation between the increase of VCAM level and C-reactive protein (CRP) in patients with different variants of CHD progression is established. Association of chronic nonspecific vascular inflammation activation and CHD destabilization is shown. The expedience of parallel determination of sVCAM and CRP levels for diagnostics of CHD destabilization and forecast elaboration is noted.

Genome-wide analysis of positively selected genes in seasonal and non-seasonal breeding species.

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Yuhuan Meng

Full Text Available Some mammals breed throughout the year, while others breed only at certain times of year. These differences in reproductive behavior can be explained by evolution. We identified positively-selected genes in two sets of species with different degrees of relatedness including seasonal and non-seasonal breeding species, using branch-site models. After stringent filtering by sum of pairs scoring, we revealed that more genes underwent positive selection in seasonal compared with non-seasonal breeding species. Positively-selected genes were verified by cDNA mapping of the positive sites with the corresponding cDNA sequences. The design of the evolutionary analysis can effectively lower the false-positive rate and thus identify valid positive genes. Validated, positively-selected genes, including CGA, DNAH1, INVS, and CD151, were related to reproductive behaviors such as spermatogenesis and cell proliferation in non-seasonal breeding species. Genes in seasonal breeding species, including THRAP3, TH1L, and CMTM6, may be related to the evolution of sperm and the circadian rhythm system. Identification of these positively-selected genes might help to identify the molecular mechanisms underlying seasonal and non-seasonal reproductive behaviors.

Destabilizing geometrical and bimaterial effects in frictional sliding

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Aldam, M.; Bar Sinai, Y.; Svetlizky, I.; Fineberg, J.; Brener, E.; Xu, S.; Ben-Zion, Y.; Bouchbinder, E.

2017-12-01

Asymmetry of the two blocks forming a fault plane, i.e. the lack of reflection symmetry with respect to the fault plane, either geometrical or material, gives rise to generic destabilizing effects associated with the elastodynamic coupling between slip and normal stress variations. While geometric asymmetry exists in various geophysical contexts, such as thrust faults and landslide systems, its effect on fault dynamics is often overlooked. In the first part of the talk, I will show that geometrical asymmetry alone can destabilize velocity-strengthening faults, which are otherwise stable. I will further show that geometrical asymmetry accounts for a significant weakening effect observed in rupture propagation and present laboratory data that support the theory. In the second part of the talk, I will focus on material asymmetry and discuss an unexpected property of the well-studied frictional bimaterial effect. I will show that while the bimaterial coupling between slip and normal stress variations is a monotonically increasing function of the bimaterial contrast, when it is coupled to interfacial shear stress perturbations through a friction law, various physical quantities exhibit a non-monotonic dependence on the bimaterial contrast. This non-monotonicity is demonstrated for the stability of steady-sliding and for unsteady rupture propagation in faults described by various friction laws (regularized Coulomb, slip-weakening, rate-and-state friction), using analytic and numerical tools. All in all, the importance of bulk asymmetry to interfacial fault dynamics is highlighted. [1] Michael Aldam, Yohai Bar-Sinai, Ilya Svetlizky, Efim A. Brener, Jay Fineberg, and Eran Bouchbinder. Frictional Sliding without Geometrical Reflection Symmetry. Phys. Rev. X, 6(4):041023, 2016. [2] Michael Aldam, Shiqing Xu, Efim A. Brener, Yehuda Ben-Zion, and Eran Bouchbinder. Non-monotonicity of the frictional bimaterial effect. arXiv:1707.01132, 2017.

Genome-wide detection and characterization of positive selection in human populations.

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Sabeti, Pardis C; Varilly, Patrick; Fry, Ben; Lohmueller, Jason; Hostetter, Elizabeth; Cotsapas, Chris; Xie, Xiaohui; Byrne, Elizabeth H; McCarroll, Steven A; Gaudet, Rachelle; Schaffner, Stephen F; Lander, Eric S; Frazer, Kelly A; Ballinger, Dennis G; Cox, David R; Hinds, David A; Stuve, Laura L; Gibbs, Richard A; Belmont, John W; Boudreau, Andrew; Hardenbol, Paul; Leal, Suzanne M; Pasternak, Shiran; Wheeler, David A; Willis, Thomas D; Yu, Fuli; Yang, Huanming; Zeng, Changqing; Gao, Yang; Hu, Haoran; Hu, Weitao; Li, Chaohua; Lin, Wei; Liu, Siqi; Pan, Hao; Tang, Xiaoli; Wang, Jian; Wang, Wei; Yu, Jun; Zhang, Bo; Zhang, Qingrun; Zhao, Hongbin; Zhao, Hui; Zhou, Jun; Gabriel, Stacey B; Barry, Rachel; Blumenstiel, Brendan; Camargo, Amy; Defelice, Matthew; Faggart, Maura; Goyette, Mary; Gupta, Supriya; Moore, Jamie; Nguyen, Huy; Onofrio, Robert C; Parkin, Melissa; Roy, Jessica; Stahl, Erich; Winchester, Ellen; Ziaugra, Liuda; Altshuler, David; Shen, Yan; Yao, Zhijian; Huang, Wei; Chu, Xun; He, Yungang; Jin, Li; Liu, Yangfan; Shen, Yayun; Sun, Weiwei; Wang, Haifeng; Wang, Yi; Wang, Ying; Xiong, Xiaoyan; Xu, Liang; Waye, Mary M Y; Tsui, Stephen K W; Xue, Hong; Wong, J Tze-Fei; Galver, Luana M; Fan, Jian-Bing; Gunderson, Kevin; Murray, Sarah S; Oliphant, Arnold R; Chee, Mark S; Montpetit, Alexandre; Chagnon, Fanny; Ferretti, Vincent; Leboeuf, Martin; Olivier, Jean-François; Phillips, Michael S; Roumy, Stéphanie; Sallée, Clémentine; Verner, Andrei; Hudson, Thomas J; Kwok, Pui-Yan; Cai, Dongmei; Koboldt, Daniel C; Miller, Raymond D; Pawlikowska, Ludmila; Taillon-Miller, Patricia; Xiao, Ming; Tsui, Lap-Chee; Mak, William; Song, You Qiang; Tam, Paul K H; Nakamura, Yusuke; Kawaguchi, Takahisa; Kitamoto, Takuya; Morizono, Takashi; Nagashima, Atsushi; Ohnishi, Yozo; Sekine, Akihiro; Tanaka, Toshihiro; Tsunoda, Tatsuhiko; Deloukas, Panos; Bird, Christine P; Delgado, Marcos; Dermitzakis, Emmanouil T; Gwilliam, Rhian; Hunt, Sarah; Morrison, Jonathan; Powell, Don; Stranger, Barbara E; Whittaker, Pamela; Bentley, David R; Daly, Mark J; de Bakker, Paul I W; Barrett, Jeff; Chretien, Yves R; Maller, Julian; McCarroll, Steve; Patterson, Nick; Pe'er, Itsik; Price, Alkes; Purcell, Shaun; Richter, Daniel J; Sabeti, Pardis; Saxena, Richa; Schaffner, Stephen F; Sham, Pak C; Varilly, Patrick; Altshuler, David; Stein, Lincoln D; Krishnan, Lalitha; Smith, Albert Vernon; Tello-Ruiz, Marcela K; Thorisson, Gudmundur A; Chakravarti, Aravinda; Chen, Peter E; Cutler, David J; Kashuk, Carl S; Lin, Shin; Abecasis, Gonçalo R; Guan, Weihua; Li, Yun; Munro, Heather M; Qin, Zhaohui Steve; Thomas, Daryl J; McVean, Gilean; Auton, Adam; Bottolo, Leonardo; Cardin, Niall; Eyheramendy, Susana; Freeman, Colin; Marchini, Jonathan; Myers, Simon; Spencer, Chris; Stephens, Matthew; Donnelly, Peter; Cardon, Lon R; Clarke, Geraldine; Evans, David M; Morris, Andrew P; Weir, Bruce S; Tsunoda, Tatsuhiko; Johnson, Todd A; Mullikin, James C; Sherry, Stephen T; Feolo, Michael; Skol, Andrew; Zhang, Houcan; Zeng, Changqing; Zhao, Hui; Matsuda, Ichiro; Fukushima, Yoshimitsu; Macer, Darryl R; Suda, Eiko; Rotimi, Charles N; Adebamowo, Clement A; Ajayi, Ike; Aniagwu, Toyin; Marshall, Patricia A; Nkwodimmah, Chibuzor; Royal, Charmaine D M; Leppert, Mark F; Dixon, Missy; Peiffer, Andy; Qiu, Renzong; Kent, Alastair; Kato, Kazuto; Niikawa, Norio; Adewole, Isaac F; Knoppers, Bartha M; Foster, Morris W; Clayton, Ellen Wright; Watkin, Jessica; Gibbs, Richard A; Belmont, John W; Muzny, Donna; Nazareth, Lynne; Sodergren, Erica; Weinstock, George M; Wheeler, David A; Yakub, Imtaz; Gabriel, Stacey B; Onofrio, Robert C; Richter, Daniel J; Ziaugra, Liuda; Birren, Bruce W; Daly, Mark J; Altshuler, David; Wilson, Richard K; Fulton, Lucinda L; Rogers, Jane; Burton, John; Carter, Nigel P; Clee, Christopher M; Griffiths, Mark; Jones, Matthew C; McLay, Kirsten; Plumb, Robert W; Ross, Mark T; Sims, Sarah K; Willey, David L; Chen, Zhu; Han, Hua; Kang, Le; Godbout, Martin; Wallenburg, John C; L'Archevêque, Paul; Bellemare, Guy; Saeki, Koji; Wang, Hongguang; An, Daochang; Fu, Hongbo; Li, Qing; Wang, Zhen; Wang, Renwu; Holden, Arthur L; Brooks, Lisa D; McEwen, Jean E; Guyer, Mark S; Wang, Vivian Ota; Peterson, Jane L; Shi, Michael; Spiegel, Jack; Sung, Lawrence M; Zacharia, Lynn F; Collins, Francis S; Kennedy, Karen; Jamieson, Ruth; Stewart, John

2007-10-18

With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts.

Science.gov (United States)

van der Lee, Robin; Wiel, Laurens; van Dam, Teunis J P; Huynen, Martijn A

2017-10-13

Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cell membrane proteins (e.g. pattern recognition, complement, cytokines, immune receptors, MHC, Siglecs). We also find evidence for positive selection in reproduction and chromosome segregation (e.g. centromere-associated CENPO, CENPT), apolipoproteins, smell/taste receptors and mitochondrial proteins. Focusing on the virus-host interaction, we retrieve most evolutionary conflicts known to influence antiviral activity (e.g. TRIM5, MAVS, SAMHD1, tetherin) and predict 70 novel cases through integration with virus-human interaction data. Protein structure analysis further identifies positive selection in the interaction interfaces between viruses and their cellular receptors (CD4-HIV; CD46-measles, adenoviruses; CD55-picornaviruses). Finally, primate PSG consistently show high sequence variation in human exomes, suggesting ongoing evolution. Our curated dataset of positive selection is a rich source for studying the genetics underlying human (antiviral) phenotypes. Procedures and data are available at https://github.com/robinvanderlee/positive-selection. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Positive diversifying selection is a pervasive adaptive force throughout the Drosophila radiation

DEFF Research Database (Denmark)

Cicconardi, Francesco; Marcatili, Paolo; Arthofer, Wolfgang

2017-01-01

The growing genomic information on non-model organisms eases exploring the evolutionary history of biodiversity. This is particularly true for Drosophila flies, in which the number of sequenced species doubled recently. Because of its outstanding diversity of species, Drosophila has become one....... grimshawi, a strong putative signal of positive diversifying selection was found related to cell, morphological, neuronal, and sensorial development and function. A recurrent signal of positive diversifying selection was found on genes related to aging and lifespan, suggesting that selection had shaped...

The signature of positive selection at randomly chosen loci.

OpenAIRE

Przeworski, Molly

2002-01-01

In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequ...

Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins.

LENUS (Irish Health Repository)

Morgan, Claire C

2010-01-01

ABSTRACT: BACKGROUND: Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the mammalia are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of mammalia. RESULTS: We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality. CONCLUSION: Our in silico analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the mammalia and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.

Signatures of positive selection in Toll-like receptor (TLR genes in mammals

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Areal Helena

2011-12-01

Full Text Available Abstract Background Toll-like receptors (TLRs are a major class of pattern recognition receptors (PRRs expressed in the cell surface or membrane compartments of immune and non-immune cells. TLRs are encoded by a multigene family and represent the first line of defense against pathogens by detecting foreigner microbial molecular motifs, the pathogen-associated molecular patterns (PAMPs. TLRs are also important by triggering the adaptive immunity in vertebrates. They are characterized by the presence of leucine-rich repeats (LRRs in the ectodomain, which are associated with the PAMPs recognition. The direct recognition of different pathogens by TLRs might result in different evolutionary adaptations important to understand the dynamics of the host-pathogen interplay. Ten mammal TLR genes, viral (TLR3, 7, 8, 9 and non-viral (TLR1-6, 10, were selected to identify signatures of positive selection that might have been imposed by interacting pathogens and to clarify if viral and non-viral TLRs might display different patterns of molecular evolution. Results By using Maximum Likelihood approaches, evidence of positive selection was found in all the TLRs studied. The number of positively selected codons (PSC ranged between 2-26 codons (0.25%-2.65% with the non-viral TLR4 as the receptor with higher percentage of positively selected codons (2.65%, followed by the viral TLR8 (2.50%. The results indicated that viral and non-viral TLRs are similarly under positive selection. Almost all TLRs have at least one PSC located in the LRR ectodomain which underlies the importance of the pathogen recognition by this region. Conclusions Our results are not in line with previous studies on primates and birds that identified more codons under positive selection in non-viral TLRs. This might be explained by the fact that both primates and birds are homogeneous groups probably being affected by only a restricted number of related viruses with equivalent motifs to be

Recruitment and selection for the packer position in a supermarket network

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Lucila Moraes Cardoso

2013-06-01

Full Text Available The method of personnel recruitment and selection is a common practice to hire people in organizations. The goal of this study is to report and to reflect about this process in a supermarket chain, which operates in food and non-food retail in the state of Sao Paulo. The purpose of the present intervention was to facilitate the recruitment and selection process for the packer position. After the intervention, we noticed an improvement on the hiring process, on the working conditions and a turnover reduction in this position.

Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency changes in polygenic adaptation.

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Stephan, Wolfgang

2016-01-01

In the past 15 years, numerous methods have been developed to detect selective sweeps underlying adaptations. These methods are based on relatively simple population genetic models, including one or two loci at which positive directional selection occurs, and one or two marker loci at which the impact of selection on linked neutral variation is quantified. Information about the phenotype under selection is not included in these models (except for fitness). In contrast, in the quantitative genetic models of adaptation, selection acts on one or more phenotypic traits, such that a genotype-phenotype map is required to bridge the gap to population genetics theory. Here I describe the range of population genetic models from selective sweeps in a panmictic population of constant size to evolutionary traffic when simultaneous sweeps at multiple loci interfere, and I also consider the case of polygenic selection characterized by subtle allele frequency shifts at many loci. Furthermore, I present an overview of the statistical tests that have been proposed based on these population genetics models to detect evidence for positive selection in the genome. © 2015 John Wiley & Sons Ltd.

Evaluation of an Improved Branch-Site Likelihood Method for Detecting Positive Selection at the Molecular Level

DEFF Research Database (Denmark)

Zhang, Jianzhi; Nielsen, Rasmus; Yang, Ziheng

2005-01-01

of interest, while test 2 had acceptable false-positive rates and appeared robust against violations of model assumptions. As test 2 is a direct test of positive selection on the lineages of interest, it is referred to as the branch-site test of positive selection and is recommended for use in real data......Detecting positive Darwinian selection at the DNA sequence level has been a subject of considerable interest. However, positive selection is difficult to detect because it often operates episodically on a few amino acid sites, and the signal may be masked by negative selection. Several methods have...... been developed to test positive selection that acts on given branches (branch methods) or on a subset of sites (site methods). Recently, Yang, Z., and R. Nielsen (2002. Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol. Biol. Evol. 19...

Genetic signature of strong recent positive selection at interleukin-32 gene in goat

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Akhtar Rasool Asif

2017-07-01

Full Text Available Objective Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. Methods By using fixation index (FST based method, IL-32 (9375 gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and FST. Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8 in Codeml program of phylogenetic analysis by maximum liklihood. Results IL-32 is detected under positive selection using the FST simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%, bison (91.97%, camel (58.39%, cat (56.59%, buffalo (56.50%, human (56.13%, dog (50.97%, horse (54.04%, and rabbit (53.41% respectively. Conclusion This study provides evidence for IL-32 gene as under significant positive selection in goat.

A genome scan for positive selection in thoroughbred horses.

Science.gov (United States)

Gu, Jingjing; Orr, Nick; Park, Stephen D; Katz, Lisa M; Sulimova, Galina; MacHugh, David E; Hill, Emmeline W

2009-06-02

Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1) deviations from expected heterozygosity (Ewens-Watterson test) in Thoroughbred (n = 112) and (2) global differentiation among four geographically diverse horse populations (F(ST)). We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; PThoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1), ACTA1 (actin, alpha 1, skeletal muscle), ACTN2 (actinin, alpha 2), ADHFE1 (alcohol dehydrogenase, iron containing, 1), MTFR1 (mitochondrial fission regulator 1), PDK4 (pyruvate dehydrogenase kinase, isozyme 4) and TNC (tenascin C). Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes within the complex molecular networks underlying obesity and its consequential pathologies, such as type 2 diabetes. Therefore, we propose Thoroughbred as a novel in vivo large animal model for understanding molecular protection against metabolic disease.

CRISPR/Cas9 allows efficient and complete knock-in of a destabilization domain-tagged essential protein in a human cell line, allowing rapid knockdown of protein function.

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Park, Arnold; Won, Sohui T; Pentecost, Mickey; Bartkowski, Wojciech; Lee, Benhur

2014-01-01

Although modulation of protein levels is an important tool for study of protein function, it is difficult or impossible to knockdown or knockout genes that are critical for cell growth or viability. For such genes, a conditional knockdown approach would be valuable. The FKBP protein-based destabilization domain (DD)-tagging approach, which confers instability to the tagged protein in the absence of the compound Shield-1, has been shown to provide rapid control of protein levels determined by Shield-1 concentration. Although a strategy to knock-in DD-tagged protein at the endogenous loci has been employed in certain parasite studies, partly due to the relative ease of knock-in as a result of their mostly haploid lifecycles, this strategy has not been demonstrated in diploid or hyperploid mammalian cells due to the relative difficulty of achieving complete knock-in in all alleles. The recent advent of CRISPR/Cas9 homing endonuclease-mediated targeted genome cleavage has been shown to allow highly efficient homologous recombination at the targeted locus. We therefore assessed the feasibility of using CRISPR/Cas9 to achieve complete knock-in to DD-tag the essential gene Treacher Collins-Franceschetti syndrome 1 (TCOF1) in human 293T cells. Using a double antibiotic selection strategy to select clones with at least two knock-in alleles, we obtained numerous complete knock-in clones within three weeks of initial transfection. DD-TCOF1 expression in the knock-in cells was Shield-1 concentration-dependent, and removal of Shield-1 resulted in destabilization of DD-TCOF1 over the course of hours. We further confirmed that the tagged TCOF1 retained the nucleolar localization of the wild-type untagged protein, and that destabilization of DD-TCOF1 resulted in impaired cell growth, as expected for a gene implicated in ribosome biogenesis. CRISPR/Cas9-mediated homologous recombination to completely knock-in a DD tag likely represents a generalizable and efficient strategy to

Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

LENUS (Irish Health Repository)

Meehan, Maria

2012-02-05

Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown. Results As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA\\'s primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. Conclusions PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.

Diagnosing MJO Destabilization and Propagation with the Moisture and MSE Budgets

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Maloney, Eric; Wolding, Brandon

2015-04-01

Novel diagnostics obtained as an extension of empirical orthogonal function analysis are used as a composting basis to gain insight into MJO dynamics through examination of reanalysis moisture and moist static energy budgets. The net effect of vertical moisture advection and cloud processes was found to be a modest positive feedback to column moisture anomalies during both enhanced and suppressed phases of the MJO. This positive feedback is regionally strengthened by anomalous surface fluxes of latent heat. The modulation of horizontal synoptic scale eddy mixing acts as a negative feedback to column moisture anomalies, while anomalous winds acting against the mean state moisture gradient aid in eastward propagation. These processes act in a systematic fashion across the Indian Ocean and oceanic regions of the Maritime Continent. The ability to approximately close the MSE budget serves an important role in constraining the moisture budget, whose residual is several times larger than the total and horizontal advective moisture tendencies. Comparison with TRMM precipitation anomalies suggests that the moisture budget residual results from an underestimation by ERAi of variations in both total precipitation and vertical moisture advection associated with the MJO. The results of this study support the concept of the MJO as a moisture-mode. This analysis is extended to examine the impact of boundary layer convergence driven by MJO SST anomalies on the vertically-integrated moisture budget. Results from a coupled version of the SP-CAM suggest that SST-driven moisture convergence anomalies are of a sufficient amplitude to be important for MJO propagation and destabilization, and may help explain why coupled models produce better simulations of the MJO than uncoupled models.

Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder.

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Renato Polimanti

2017-02-01

Full Text Available The human brain is the outcome of innumerable evolutionary processes; the systems genetics of psychiatric disorders could bear their signatures. On this basis, we analyzed five psychiatric disorders, attention deficit hyperactivity disorder, autism spectrum disorder (ASD, bipolar disorder, major depressive disorder, and schizophrenia (SCZ, using GWAS summary statistics from the Psychiatric Genomics Consortium. Machine learning-derived scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele reached fixation and incomplete selection (loci where a selected allele has not yet reached fixation. ASD GWAS results positively correlated with incomplete-selection (p = 3.53*10-4. Variants with ASD GWAS p<0.1 were shown to have a 19%-increased probability to be in the top-5% for incomplete-selection score (OR = 1.19, 95%CI = 1.11-1.8, p = 9.56*10-7. Investigating the effect directions of minor alleles, we observed an enrichment for positive associations in SNPs with ASD GWAS p<0.1 and top-5% incomplete-selection score (permutation p<10-4. Considering the set of these ASD-positive-associated variants, we observed gene-expression enrichments for brain and pituitary tissues (p = 2.3*10-5 and p = 3*10-5, respectively and 53 gene ontology (GO enrichments, such as nervous system development (GO:0007399, p = 7.57*10-12, synapse organization (GO:0050808, p = 8.29*10-7, and axon guidance (GO:0007411, p = 1.81*10-7. Previous genetic studies demonstrated that ASD positively correlates with childhood intelligence, college completion, and years of schooling. Accordingly, we hypothesize that certain ASD risk alleles were under positive selection during human evolution due to their involvement in neurogenesis and cognitive ability.

Thermodynamics of protein destabilization in live cells.

Science.gov (United States)

Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andres; Theillet, François-Xavier; Bekei, Beata; Logan, Derek T; Selenko, Philipp; Wennerström, Håkan; Oliveberg, Mikael

2015-10-06

Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.

Modeling of sawtooth destabilization during radio-frequency heating experiments in tokamak plasmas

International Nuclear Information System (INIS)

McClements, K.G.; Dendy, R.O.; Hastie, R.J.; Martin, T.J.

1996-01-01

Sawtooth oscillations in tokamaks have been stabilized using ion cyclotron resonance heating (ICRH), but often reappear while ICRH continues. It is shown that the reappearance of sawteeth during one particular ICRH discharge in the Joint European Torus (JET) [Campbell et al., Phys. Rev. Lett. 60, 2148 (1988)] was correlated with a change of sign in the energy δW associated with m=1 internal kink displacements. To compute δW, a new analytical model is used for the distribution function of heated minority ions, which is consistent with Fokker endash Planck simulations of ICRH. Minority ions have a stabilizing influence, arising from third adiabatic invariant conservation, but also contribute to a destabilizing shift of magnetic flux surfaces. As the minor radius of the q=1 surface rises, the stabilizing influence of minority ions diminishes, and the shape of the plasma cross section becomes increasingly important. It is shown that an increase in ICRH power can destabilize the kink mode: this is consistent with observations of sawteeth in JET discharges with varying levels of ICRH. It is suggested that the sawtooth-free period could be prolonged by minimizing the vertical extent of the ICRH power deposition profile.1996 American Institute of Physics

Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences

Science.gov (United States)

König, Sebastian L. B.; Huppert, Julian L.; Sigel, Roland K. O.; Evans, Amanda C.

2013-01-01

G-quadruplexes and i-motifs are complementary examples of non-canonical nucleic acid substructure conformations. G-quadruplex thermodynamic stability has been extensively studied for a variety of base sequences, but the degree of duplex destabilization that adjacent quadruplex structure formation can cause has yet to be fully addressed. Stable in vivo formation of these alternative nucleic acid structures is likely to be highly dependent on whether sufficient spacing exists between neighbouring duplex- and quadruplex-/i-motif-forming regions to accommodate quadruplexes or i-motifs without disrupting duplex stability. Prediction of putative G-quadruplex-forming regions is likely to be assisted by further understanding of what distance (number of base pairs) is required for duplexes to remain stable as quadruplexes or i-motifs form. Using oligonucleotide constructs derived from precedented G-quadruplexes and i-motif-forming bcl-2 P1 promoter region, initial biophysical stability studies indicate that the formation of G-quadruplex and i-motif conformations do destabilize proximal duplex regions. The undermining effect that quadruplex formation can have on duplex stability is mitigated with increased distance from the duplex region: a spacing of five base pairs or more is sufficient to maintain duplex stability proximal to predicted quadruplex/i-motif-forming regions. PMID:23771141

Evidence for positive selection in putative virulence factors within the Paracoccidioides brasiliensis species complex.

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Daniel R Matute

Full Text Available Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin America. Recently, the existence of three genetically isolated groups in P. brasiliensis was demonstrated, enabling comparative studies of molecular evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for putative virulence factors were analyzed to determine whether they were under positive selection. Our maximum likelihood-based approach yielded evidence for selection in 12 genes that are involved in different cellular processes. An in-depth analysis of four of these genes showed them to be either antigenic or involved in pathogenesis. Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection. The other three genes (fks, cdc42 and p27 show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection. Our results are consistent with the more general observations that selective constraints are variable across the genome, and that even in the genes under positive selection, only a few sites are altered. We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

Tracing evolutionary relicts of positive selection on eight malaria-related immune genes in mammals.

Science.gov (United States)

Huang, Bing-Hong; Liao, Pei-Chun

2015-07-01

Plasmodium-induced malaria widely infects primates and other mammals. Multiple past studies have revealed that positive selection could be the main evolutionary force triggering the genetic diversity of anti-malaria resistance-associated genes in human or primates. However, researchers focused most of their attention on the infra-generic and intra-specific genome evolution rather than analyzing the complete evolutionary history of mammals. Here we extend previous research by testing the evolutionary link of natural selection on eight candidate genes associated with malaria resistance in mammals. Three of the eight genes were detected to be affected by recombination, including TNF-α, iNOS and DARC. Positive selection was detected in the rest five immunogenes multiple times in different ancestral lineages of extant species throughout the mammalian evolution. Signals of positive selection were exposed in four malaria-related immunogenes in primates: CCL2, IL-10, HO1 and CD36. However, selection signals of G6PD have only been detected in non-primate eutherians. Significantly higher evolutionary rates and more radical amino acid replacement were also detected in primate CD36, suggesting its functional divergence from other eutherians. Prevalent positive selection throughout the evolutionary trajectory of mammalian malaria-related genes supports the arms race evolutionary hypothesis of host genetic response of mammalian immunogenes to infectious pathogens. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Poliovirus-associated protein kinase: Destabilization of the virus capsid and stimulation of the phosphorylation reaction by Zn2+

International Nuclear Information System (INIS)

Ratka, M.; Lackmann, M.; Ueckermann, C.; Karlins, U.; Koch, G.

1989-01-01

The previously described poliovirus-associated protein kinase activity phosphorylates viral proteins VP0 and VP2 as well as exogenous proteins in the presence of Mg 2+ . In this paper, the effect of Zn 2+ on the phosphorylation reaction and the stability of the poliovirus capsid has been studied in detail and compared to that of Mg 2+ . In the presence of Zn 2+ , phosphorylation of capsid proteins VP2 and VP4 is significantly higher while phosphorylation of VP0 and exogenous phosphate acceptor proteins is not detected. The results indicate the activation of more than one virus-associated protein kinase by Zn 2+ . The ion-dependent behavior of the enzyme activities is observed independently of whether the virus was obtained from HeLa or green monkey kidney cells. The poliovirus capsid is destabilized by Zn 2+ . This alteration of the poliovirus capsid structure is a prerequisite for effective phosphorylation of viral capsid proteins. The increased level of phosphorylation of viral capsid proteins results in further destabilization of the viral capsid. As a result of the conformational changes, poliovirus-associated protein kinase activities dissociate from the virus particle. The authors suggest that the destabilizing effect of phosphorylation on the viral capsid plays a role in uncoating of poliovirus

Improved exogenous DNA uptake in bovine spermatozoa and gene expression in embryos using membrane destabilizing agents in ICSI-SMGT.

Science.gov (United States)

Sánchez-Villalba, Esther; Arias, María Elena; Zambrano, Fabiola; Loren, Pía; Felmer, Ricardo

2018-02-01

Sperm-mediated gene transfer (SMGT) is a simple, fast, and economical biotechnological tool for producing transgenic animals. However, transgene expression with this technique in bovine embryos is still inefficient due to low uptake and binding of exogenous DNA in spermatozoa. The present study evaluated the effects of sperm membrane destabilization on the binding capacity, location and quantity of bound exogenous DNA in cryopreserved bovine spermatozoa using Triton X-100 (TX-100), lysolecithin (LL) and sodium hydroxide (NaOH). Effects of these treatments were also evaluated by intracytoplasmic sperm injection (ICSI)-SMGT. Results showed that all treatments bound exogenous DNA to spermatozoa including the control. Spermatozoa treated with different membrane destabilizing agents bound the exogenous DNA throughout the head and tail of spermatozoa, compared with the control, in which binding occurred mainly in the post-acrosomal region and tail. The amount of exogenous DNA bound to spermatozoa was much higher for the different sperm treatments than the control (P Exogenous gene expression in embryos was also improved by these treatments. These results demonstrated that sperm membrane destabilization could be a novel strategy in bovine SMGT protocols for the generation of transgenic embryos by ICSI.

Gravity-induced encapsulation of liquids by destabilization of granular rafts

Science.gov (United States)

Abkarian, Manouk; Protière, Suzie; Aristoff, Jeffrey M.; Stone, Howard A.

2013-05-01

Droplets and bubbles coated by a protective armour of particles find numerous applications in encapsulation, stabilization of emulsions and foams, and flotation techniques. Here we study the role of a body force, such as in flotation, as a means of continuous encapsulation by particles. We use dense particles, which self-assemble into rafts, at oil-water interfaces. We show that these rafts can be spontaneously or controllably destabilized into armoured oil-in-water droplets, which highlights a possible role for common granular materials in environmental remediation. We further present a method for continuous production and discuss the generalization of our approach towards colloidal scales.

The role of positive selection in determining the molecular cause of species differences in disease

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Foord Steven M

2008-10-01

Full Text Available Abstract Background Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes. Results We identified genes that putatively underwent positive selection during the evolution of humans and four mammals which are often used to model human diseases (mouse, rat, chimpanzee and dog. We show that genes predicted to have been subject to positive selection pressure during human evolution are implicated in diseases such as epithelial cancers, schizophrenia, autoimmune diseases and Alzheimer's disease, all of which differ in prevalence and symptomatology between humans and their mammalian relatives. In agreement with previous studies, the chimpanzee lineage was found to have more genes under positive selection than any of the other lineages. In addition, we found new evidence to support the hypothesis that genes that have undergone positive selection tend to interact with each other. This is the first such evidence to be detected widely among mammalian genes and may be important in identifying molecular pathways causative of species differences. Conclusion Our dataset of genes predicted to have been subject to positive selection in five species serves as an informative resource that can be consulted prior to selecting appropriate animal models during drug target validation. We conclude that studying the evolution of functional and biomedical disease differences

Stabilizing and destabilizing forces in the nursing work environment: a qualitative study on turnover intention.

Science.gov (United States)

Choi, Sandy Pin-Pin; Pang, Samantha Mei-Che; Cheung, Kin; Wong, Thomas Kwok-Shing

2011-10-01

The nursing work environment, which provides the context of care delivery, has been gaining increasing attention in recent years. A growing body of evidence points to an inseparable link between attributes of the nursing work environment and nurse and patient outcomes. While most studies have adopted a survey design to examine the workforce and work environment issues, this study employed a phenomenological approach to provide empirical evidence regarding nurses' perceptions of their work and work environment. The aim of this study was to advance our understanding of the phenomenon of increasing nurse turnover through exploring frontline registered nurses' lived experiences of working in Hong Kong public hospitals. A modified version of Van Kaam's controlled explication method was adopted. Individual semi-structured interviews were conducted with 26 frontline nurses recruited from ten acute regional, district and non-acute public hospitals in Hong Kong. Their perspectives in regard to their work and work environment, such as workload, manpower demand and professional values, were extensively examined, and a hypothetical description relating the nursing work environment with nurses' turnover intention was posited. Contemplation of nurses' experiences revealed the vulnerable aspects of nursing work and six essential constituents of the nursing work environment, namely staffing level, work responsibility, management, co-worker relationships, job, and professional incentives. These essential constituents have contributed to two sets of forces, stabilizing and destabilizing forces, which originate from the attributes of the nursing work environment. Nurses viewed harmonious co-worker relationships, recognition and professional development as the crucial retaining factors. However, nurses working in an unfavorable environment were overwhelmed by destabilizing forces; they expressed frustration and demonstrated an intention to leave their work environment. The nursing

A genome scan for positive selection in thoroughbred horses.

Directory of Open Access Journals (Sweden)

Jingjing Gu

2009-06-01

Full Text Available Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1 deviations from expected heterozygosity (Ewens-Watterson test in Thoroughbred (n = 112 and (2 global differentiation among four geographically diverse horse populations (F(ST. We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; P<0.01, insulin receptor signalling (5.0-fold enrichment; P<0.01 and lipid transport (2.2-fold enrichment; P<0.05 genes. We found a significant overrepresentation of sarcoglycan complex (11.1-fold enrichment; P<0.05 and focal adhesion pathway (1.9-fold enrichment; P<0.01 genes highlighting the role for muscle strength and integrity in the Thoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1, ACTA1 (actin, alpha 1, skeletal muscle, ACTN2 (actinin, alpha 2, ADHFE1 (alcohol dehydrogenase, iron containing, 1, MTFR1 (mitochondrial fission regulator 1, PDK4 (pyruvate dehydrogenase kinase, isozyme 4 and TNC (tenascin C. Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes

A Demonstration of Regression False Positive Selection in Data Mining

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Pinder, Jonathan P.

2014-01-01

Business analytics courses, such as marketing research, data mining, forecasting, and advanced financial modeling, have substantial predictive modeling components. The predictive modeling in these courses requires students to estimate and test many linear regressions. As a result, false positive variable selection ("type I errors") is…

Positive selection for unpreferred codon usage in eukaryotic genomes

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Galagan James E

2007-07-01

Full Text Available Abstract Background Natural selection has traditionally been understood as a force responsible for pushing genes to states of higher translational efficiency, whereas lower translational efficiency has been explained by neutral mutation and genetic drift. We looked for evidence of directional selection resulting in increased unpreferred codon usage (and presumably reduced translational efficiency in three divergent clusters of eukaryotic genomes using a simple optimal-codon-based metric (Kp/Ku. Results Here we show that for some genes natural selection is indeed responsible for causing accelerated unpreferred codon substitution, and document the scope of this selection. In Cryptococcus and to a lesser extent Drosophila, we find many genes showing a statistically significant signal of selection for unpreferred codon usage in one or more lineages. We did not find evidence for this type of selection in Saccharomyces. The signal of positive selection observed from unpreferred synonymous codon substitutions is coincident in Cryptococcus and Drosophila with the distribution of upstream open reading frames (uORFs, another genic feature known to reduce translational efficiency. Functional enrichment analysis of genes exhibiting low Kp/Ku ratios reveals that genes in regulatory roles are particularly subject to this type of selection. Conclusion Through genome-wide scans, we find recent selection for unpreferred codon usage at approximately 1% of genetic loci in a Cryptococcus and several genes in Drosophila. Unpreferred codons can impede translation efficiency, and we find that genes with translation-impeding uORFs are enriched for this selection signal. We find that regulatory genes are particularly likely to be subject to selection for unpreferred codon usage. Given that expression noise can propagate through regulatory cascades, and that low translational efficiency can reduce expression noise, this finding supports the hypothesis that translational

Positive selection on gene expression in the human brain

DEFF Research Database (Denmark)

Khaitovich, Philipp; Tang, Kun; Franz, Henriette

2006-01-01

Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

Structural determinants of HIV-1 nucleocapsid protein for cTAR DNA binding and destabilization, and correlation with inhibition of self-primed DNA synthesis.

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Beltz, Hervé; Clauss, Céline; Piémont, Etienne; Ficheux, Damien; Gorelick, Robert J; Roques, Bernard; Gabus, Caroline; Darlix, Jean-Luc; de Rocquigny, Hugues; Mély, Yves

2005-05-20

The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) is formed of two highly conserved CCHC zinc fingers flanked by small basic domains. NC is required for the two obligatory strand transfers in viral DNA synthesis through its nucleic acid chaperoning properties. The first DNA strand transfer relies on NC's ability to bind and destabilize the secondary structure of complementary transactivation response region (cTAR) DNA, to inhibit self-priming, and to promote the annealing of cTAR to TAR RNA. To further investigate NC chaperone properties, our aim was to identify by fluorescence spectroscopy and gel electrophoresis, the NC structural determinants for cTAR binding and destabilization, and for the inhibition of self-primed DNA synthesis on a model system using a series of NC mutants and HIV-1 reverse transcriptase. NC destabilization and self-priming inhibition properties were found to be supported by the two fingers in their proper context and the basic (29)RAPRKKG(35) linker. The strict requirement of the native proximal finger suggests that its hydrophobic platform (Val13, Phe16, Thr24 and Ala25) is crucial for binding, destabilization and inhibition of self-priming. In contrast, only partial folding of the distal finger is required, probably for presenting the Trp37 residue in an appropriate orientation. Also, Trp37 and the hydrophobic residues of the proximal finger appear to be essential for the propagation of the melting from the cTAR ends up to the middle of the stem. Finally, both N-terminal and C-terminal basic domains contribute to cTAR binding but not to its destabilization.

PSP: rapid identification of orthologous coding genes under positive selection across multiple closely related prokaryotic genomes.

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Su, Fei; Ou, Hong-Yu; Tao, Fei; Tang, Hongzhi; Xu, Ping

2013-12-27

With genomic sequences of many closely related bacterial strains made available by deep sequencing, it is now possible to investigate trends in prokaryotic microevolution. Positive selection is a sub-process of microevolution, in which a particular mutation is favored, causing the allele frequency to continuously shift in one direction. Wide scanning of prokaryotic genomes has shown that positive selection at the molecular level is much more frequent than expected. Genes with significant positive selection may play key roles in bacterial adaption to different environmental pressures. However, selection pressure analyses are computationally intensive and awkward to configure. Here we describe an open access web server, which is designated as PSP (Positive Selection analysis for Prokaryotic genomes) for performing evolutionary analysis on orthologous coding genes, specially designed for rapid comparison of dozens of closely related prokaryotic genomes. Remarkably, PSP facilitates functional exploration at the multiple levels by assignments and enrichments of KO, GO or COG terms. To illustrate this user-friendly tool, we analyzed Escherichia coli and Bacillus cereus genomes and found that several genes, which play key roles in human infection and antibiotic resistance, show significant evidence of positive selection. PSP is freely available to all users without any login requirement at: http://db-mml.sjtu.edu.cn/PSP/. PSP ultimately allows researchers to do genome-scale analysis for evolutionary selection across multiple prokaryotic genomes rapidly and easily, and identify the genes undergoing positive selection, which may play key roles in the interactions of host-pathogen and/or environmental adaptation.

Positively selected sites in cetacean myoglobins contribute to protein stability

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Dasmeh, Pouria; Serohijos, Adrian W R; Kepp, Kasper P

2013-01-01

Since divergence ∼50 Ma ago from their terrestrial ancestors, cetaceans underwent a series of adaptations such as a ∼10-20 fold increase in myoglobin (Mb) concentration in skeletal muscle, critical for increasing oxygen storage capacity and prolonging dive time. Whereas the O2-binding affinity...... between Mb folding stability and protein abundance, suggesting that a selection pressure for stability acts proportionally to higher expression. We also identify a major divergence event leading to the common ancestor of whales, during which major stabilization occurred. Most of the positively selected...

Continental-scale footprint of balancing and positive selection in a small rodent (Microtus arvalis.

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Martin C Fischer

Full Text Available Genetic adaptation to different environmental conditions is expected to lead to large differences between populations at selected loci, thus providing a signature of positive selection. Whereas balancing selection can maintain polymorphisms over long evolutionary periods and even geographic scale, thus leads to low levels of divergence between populations at selected loci. However, little is known about the relative importance of these two selective forces in shaping genomic diversity, partly due to difficulties in recognizing balancing selection in species showing low levels of differentiation. Here we address this problem by studying genomic diversity in the European common vole (Microtus arvalis presenting high levels of differentiation between populations (average F ST = 0.31. We studied 3,839 Amplified Fragment Length Polymorphism (AFLP markers genotyped in 444 individuals from 21 populations distributed across the European continent and hence over different environmental conditions. Our statistical approach to detect markers under selection is based on a Bayesian method specifically developed for AFLP markers, which treats AFLPs as a nearly codominant marker system, and therefore has increased power to detect selection. The high number of screened populations allowed us to detect the signature of balancing selection across a large geographic area. We detected 33 markers potentially under balancing selection, hence strong evidence of stabilizing selection in 21 populations across Europe. However, our analyses identified four-times more markers (138 being under positive selection, and geographical patterns suggest that some of these markers are probably associated with alpine regions, which seem to have environmental conditions that favour adaptation. We conclude that despite favourable conditions in this study for the detection of balancing selection, this evolutionary force seems to play a relatively minor role in shaping the genomic

Positive selection on D-lactate dehydrogenases of Lactobacillus delbrueckii subspecies bulgaricus.

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Zhang, Jifeng; Gong, Guangyu; Wang, Xiao; Zhang, Hao; Tian, Weidong

2015-08-01

Lactobacillus delbrueckii has been widely used for yogurt fermentation. It has genes encoding both D- and L-type lactate dehydrogenases (LDHs) that catalyse the production of L(+) or D(-) stereoisomer of lactic acid. D-lactic acid is the primary lactate product by L. delbrueckii, yet it cannot be metabolised by human intestine. Since it has been domesticated for long time, an interesting question arises regarding to whether the selection pressure has affected the evolution of both L-LDH and D-LDH genes in the genome. To answer this question, in this study the authors first investigated the evolution of these two genes by constructing phylogenetic trees. They found that D-LDH-based phylogenetic tree could better represent the phylogenetic relationship in the acidophilus complex than L-LDH-based tree. They next investigated the evolutions of LDH genes of L. delbrueckii at amino acid level, and found that D-LDH gene in L. delbrueckii is positively selected, possibly a consequence of long-term domestication. They further identified four amino acids that are under positive selection. One of them, V261, is located at the centre of three catalytic active sites, indicating likely functional effects on the enzyme activity. The selection from the domestication process thus provides direction for future engineering of D-LDH.

Mathematical Optimization Algorithm for Minimizing the Cost Function of GHG Emission in AS/RS Using Positive Selection Based Clonal Selection Principle

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Mahalakshmi; Murugesan, R.

2018-04-01

This paper regards with the minimization of total cost of Greenhouse Gas (GHG) efficiency in Automated Storage and Retrieval System (AS/RS). A mathematical model is constructed based on tax cost, penalty cost and discount cost of GHG emission of AS/RS. A two stage algorithm namely positive selection based clonal selection principle (PSBCSP) is used to find the optimal solution of the constructed model. In the first stage positive selection principle is used to reduce the search space of the optimal solution by fixing a threshold value. In the later stage clonal selection principle is used to generate best solutions. The obtained results are compared with other existing algorithms in the literature, which shows that the proposed algorithm yields a better result compared to others.

Critical thinking of destabilizing interpretations of events and phenomena: the role of economic sciences

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Тетяна Андріївна Непокупна

2015-03-01

Full Text Available This article analyzes the global transformations and their impact on the main society life; the specifics of modern interpretations of events and phenomena, their destabilizing effects on behavior, health and life of humans; the role of economic sciences in the formation of critical thinking as a means of combating ignorance and propaganda, formation of an objective world view that grounded on knowledge

Evidence for positive selection on the leptin gene in Cetacea and Pinnipedia.

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Li Yu

Full Text Available The leptin gene has received intensive attention and scientific investigation for its importance in energy homeostasis and reproductive regulation in mammals. Furthermore, study of the leptin gene is of crucial importance for public health, particularly for its role in obesity, as well as for other numerous physiological roles that it plays in mammals. In the present work, we report the identification of novel leptin genes in 4 species of Cetacea, and a comparison with 55 publicly available leptin sequences from mammalian genome assemblies and previous studies. Our study provides evidence for positive selection in the suborder Odontoceti (toothed whales of the Cetacea and the family Phocidae (earless seals of the Pinnipedia. We also detected positive selection in several leptin gene residues in these two lineages. To test whether leptin and its receptor evolved in a coordinated manner, we analyzed 24 leptin receptor gene (LPR sequences from available mammalian genome assemblies and other published data. Unlike the case of leptin, our analyses did not find evidence of positive selection for LPR across the Cetacea and Pinnipedia lineages. In line with this, positively selected sites identified in the leptin genes of these two lineages were located outside of leptin receptor binding sites, which at least partially explains why co-evolution of leptin and its receptor was not observed in the present study. Our study provides interesting insights into current understanding of the evolution of mammalian leptin genes in response to selective pressures from life in an aquatic environment, and leads to a hypothesis that new tissue specificity or novel physiologic functions of leptin genes may have arisen in both odontocetes and phocids. Additional data from other species encompassing varying life histories and functional tests of the adaptive role of the amino acid changes identified in this study will help determine the factors that promote the adaptive

A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees

DEFF Research Database (Denmark)

Nielsen, Rasmus; Bustamente, Carlos; Clark, Andrew G.

2005-01-01

Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect...... such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved...

Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

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Elisa Dominguez

Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

Positive selection on a bacterial oncoprotein associated with gastric cancer

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Delgado-Rosado Gisela

2011-11-01

Full Text Available Background Helicobacter pylori is a vertically inherited gut commensal that is carcinogenic if it possesses the cag pathogenicity island (cag PaI; infection with H.pylori is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO. The cag PaI locus encodes the cagA gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the cag PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking. Results Here, we reveal that the cagA gene displays strong signatures of positive selection in bacteria isolated from amerindian populations, using the Ka/Ks ratio. Weaker signatures are also detected in the gene from bacteria isolated from asian populations, using the Ka/Ks ratio and the more sensitive branches-sites model of the PAML package. When the cagA gene isolated from amerindian populations was examined in more detail it was found that the region under positive selection contains the EPIYA domains, which are known to modulate the carcinogenicity of the gene. This means that the carcinogenicity modulating region of the gene is undergoing adaptation. The results are discussed in relation to the high incidences of stomach cancer in some latin american and asian populations. Conclusion Positive selection on cagA indicates antagonistic coevolution between host and bacteria, which appears paradoxical given that cagA is detrimental to the human host upon which the bacteria depends. This suggests several non-exclusive possibilities; that gastric cancer has not been a major selective pressure on human populations, that cagA has an undetermined benefit to the human host, or that horizontal transmission of H.pylori between hosts

Positive allometry and the prehistory of sexual selection.

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Tomkins, Joseph L; LeBas, Natasha R; Witton, Mark P; Martill, David M; Humphries, Stuart

2010-08-01

The function of the exaggerated structures that adorn many fossil vertebrates remains largely unresolved. One recurrent hypothesis is that these elaborated traits had a role in thermoregulation. This orthodoxy persists despite the observation that traits exaggerated to the point of impracticality in extant organisms are almost invariably sexually selected. We use allometric scaling to investigate the role of sexual selection and thermoregulation in the evolution of exaggerated traits of the crested pterosaur Pteranodon longiceps and the sail-backed eupelycosaurs Dimetrodon and Edaphosaurus. The extraordinarily steep positive allometry of the head crest of Pteranodon rules out all of the current hypotheses for this trait's main function other than sexual signaling. We also find interspecific patterns of allometry and sexual dimorphism in the sails of Dimetrodon and patterns of elaboration in Edaphosaurus consistent with a sexually selected function. Furthermore, small ancestral, sail-backed pelycosaurs would have been too small to need adaptations to thermoregulation. Our results question the popular view that the elaborated structures of these fossil species evolved as thermoregulatory organs and provide evidence in support of the hypothesis that Pteranodon crests and eupelycosaur sails are among the earliest and most extreme examples of elaborate sexual signals in the evolution of terrestrial vertebrates.

Destabilization of counter-propagating TAEs by off-axis, co-current Neutral Beam Injection

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Podesta', M.; Fredrickson, E.; Gorelenkova, M.

2017-10-01

Neutral Beam injection (NBI) is a common tool to heat the plasma and drive current non-inductively in fusion devices. Energetic particles (EP) resulting from NBI can drive instabilities that are detrimental for the performance and the predictability of plasma discharges. A broad NBI deposition profile, e.g. by off-axis injection aiming near the plasma mid-radius, is often assumed to limit those undesired effects by reducing the radial gradient of the EP density, thus reducing the ``universal'' drive for instabilities. However, this work presents new evidence that off-axis NBI can also lead to undesired effects such as the destabilization of Alfvénic instabilities, as observed in NSTX-U plasmas. Experimental observations indicate that counter propagating toroidal AEs are destabilized as the radial EP density profile becomes hollow as a result of off-axis NBI. Time-dependent analysis with the TRANSP code, augmented by a reduced fast ion transport model (known as kick model), indicates that instabilities are driven by a combination of radial and energy gradients in the EP distribution. Understanding the mechanisms for wave-particle interaction, revealed by the phase space resolved analysis, is the basis to identify strategies to mitigate or suppress the observed instabilities. Work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Contract Number DE-AC02-09CH11466.

The role of positive selection in hepatitis C virus.

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Cuevas, José M; Gonzalez, Michael; Torres-Puente, Manuela; Jiménez-Hernández, Nuria; Bracho, María A; García-Robles, Inmaculada; González-Candelas, Fernando; Moya, Andrés

2009-09-01

Hepatitis C virus (HCV) is a major health problem worldwide, infecting an estimated 170 million people. In this study, we have employed a large data set of sequences (14,654 sequences from between 25 and 100 clone sequences per analyzed region and per patient) from 67 patients infected with HCV genotype 1 (23 subtype 1a and 44 subtype 1b). For all patients, a sample prior to combined therapy with alpha interferon plus ribavirin was available, whereas for some patients additional samples after 6 or 12 months of treatment were also available. Twenty-seven patients responded to treatment (12 subtype 1a and 15 subtype 1b) and forty patients did not respond to treatment (11 subtype 1a vs. 29 subtype 1b). Two regions of the HCV genome were analyzed, one compressing the hypervariable regions (HVR1, HVR2 and HVR3) of the envelope 2 glycoprotein and another one including the interferon sensitive determining region (ISDR) and the V3 domain of the NS5A protein. Previously (Cuevas, J.M., Torres-Puente, M., Jiménez-Hernández, N., Bracho, M.A., García-Robles, I., Wrobel, B., Carnicer, F., del Olmo, J., Ortega, E., Moya, A., González-Candelas, F., 2008b. Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin. Plos One 3 (8), e3058), several amino acid positions in both regions analyzed were detected to be under positive selection. Here, we have compared the amino acid composition of each positively selected position between responder and non-responder patients for both subtypes. If we exclude some non-conclusive cases, no clear differences were detected in any case. In conclusion, identifying specific positions as completely discriminatory of treatment response seems to be a difficult task. Our results, in concordance with previous studies, suggest that HCV evasion strategies are more likely based on a global increased variability, which would yield combinations of mutations with an increased resistance, than on the fixation of

Influence of molybdenum on hardenability of destabilized high chromium cast irons. Ko kuromu chutetsu no netsushori tokusei ni oyobosu moribuden no eikyo

Energy Technology Data Exchange (ETDEWEB)

Kuwano, M. (Ube, Collete of Technology, Yamaguchi (Japan)); Ogi, K. (Kyushu University, Fukuoka (Japan). Faculty of Engineering); Sawamoto, A. (Yamaguchi University, Yamaguchi (Japan))

1991-07-25

Alloy elements are added to compensate for reduction in hardenability of high chromium cast iron as a result of destabilization heat treatment. With the purpose of investigating the influence of the added elements, this paper describes investigations made on effects of Mo and destabilization heat treatment conditions on martensite transformation , eutectoid transformation and base hardness, using Fe-Cr-C-based alloy containing C at 1.6-3.6%, and Cr at 6.6-26%. The main results obtained are as follows: Mo and Cr had the distribution coefficient for initial crystal austenite is smaller than one and were microscopically segregated in the dendrite base; the solute element distribution in the base is homogenized as a result of the long-time destabilization heat treatment while the Cr and C concentrations reduce largely, and the Mo concentration increases slightly; Mo has little influence on the Ms point, and reduces with the smaller the Cr/C ratio and the higher the retention temperature; and the base hardness corresponds well to a CCT diagram. 14 refs., 11 figs., 1 tab.

Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes glareolus).

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Scherman, Kristin; Råberg, Lars; Westerdahl, Helena

2014-05-01

The major histocompatibility complex (MHC) class IIB genes show considerable sequence similarity between loci. The MHC class II DQB and DRB genes are known to exhibit a high level of polymorphism, most likely maintained by parasite-mediated selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has been given much less attention. Here, we characterised DQB genes in Swedish bank voles Myodes glareolus, using full-length transcripts. We then designed primers that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and investigated molecular signatures of natural selection on DRB and DQB alleles. The presence of two separate gene clusters was confirmed using BLASTN and phylogenetic analysis, where our seven transcripts clustered according to either DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles per individual as previously published DRB primers, though our reads are longer. Traditional d N/d S analyses of DRB sequences in the bank vole have not found a conclusive signal of positive selection. Using a more advanced substitution model (the Kumar method) we found positive selection in the peptide binding region (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions detected positively selected sites located in the PBR of both DQB and DRB. Interestingly, these analyses detected at least twice as many positively selected sites in DQB than DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time.

Flexible selection process based on skills applied to the communication manager position

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Rita Jácome López

2016-03-01

Full Text Available The Communication Manager position is relevant to the reputation of an organization, because it influences through its own personal image and reputation; therefore, the selection of this manager has to be painstaking. In this paper we propose a flexible selection process based on fuzzy logic, to fit the skills of candidates for the job and to support decision making. We present two techniques:one that selects the best applicant and another one that compares candidates with an ideal constructed with information provided by Spanish managers.

Destabilization of Titania Nanosheet Suspensions by Inorganic Salts: Hofmeister Series and Schulze-Hardy Rule.

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Rouster, Paul; Pavlovic, Marko; Szilagyi, Istvan

2017-07-13

Ion specific effects on colloidal stability of titania nanosheets (TNS) were investigated in aqueous suspensions. The charge of the particles was varied by the pH of the solutions, therefore, the influence of mono- and multivalent anions on the charging and aggregation behavior could be studied when they were present either as counter or co-ions in the systems. The aggregation processes in the presence of inorganic salts were mainly driven by interparticle forces of electrostatic origin, however, chemical interactions between more complex ions and the surface led to additional attractive forces. The adsorption of anions significantly changed the surface charge properties and hence, the resistance of the TNS against salt-induced aggregation. On the basis of their ability in destabilization of the dispersions, the monovalent ions could be ordered according to the Hofmeister series in acidic solutions, where they act as counterions. However, the behavior of the biphosphate anion was atypical and its adsorption induced charge reversal of the particles. The multivalent anions destabilized the oppositely charged TNS more effectively and the aggregation processes followed the Schulze-Hardy rule. Only weak or negligible interactions were observed between the anions and the particles in alkaline suspensions, where the TNS possessed negative charge.

Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups

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He Shao-Heng

2006-10-01

Full Text Available Abstract Background It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS coronavirus (CoV is the cause of the SARS outbreak worldwide. The spike (S protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown. Results By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163 in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24% of positively selected sites was located in receptor-binding domain (RBD than in heptad repeat (HR1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208, and a greater percentage (25% of these sites occurred in HR1–HR2 region than in RBD in 03-early

The Destabilization of Protected Soil Organic Carbon Following Experimental Drought at the Pore and Core scale

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Smith, A. P.; Bond-Lamberty, B. P.; Tfaily, M. M.; Todd-Brown, K. E.; Bailey, V. L.

2015-12-01

The movement of water and solutes through the pore matrix controls the distribution and transformation of carbon (C) in soils. Thus, a change in the hydrologic connectivity, such as increased saturation, disturbance or drought, may alter C mineralization and greenhouse gas (GHG) fluxes to the atmosphere. While these processes occur at the pore scale, they are often investigated at coarser scale. This project investigates pore- and core-scale soil C dynamics with varying hydrologic factors (simulated precipitation, groundwater-led saturation, and drought) to assess how climate-change induced shifts in hydrologic connectivity influences the destabilization of protected C in soils. Surface soil cores (0-15 cm depth) were collected from the Disney Wilderness Preserve, Florida, USA where water dynamics, particularly water table rise and fall, appear to exert a strong control on the emissions of GHGs and the persistence of soil organic matter in these soils. We measured CO2 and CH4 from soils allowed to freely imbibe water from below to a steady state starting from either field moist conditions or following experimental drought. Parallel treatments included the addition of similar quantities of water from above to simulate precipitation. Overall respiration increased in soil cores subjected to drought compared to field moist cores independent of wetting type. Cumulative CH4 production was higher in drought-induced soils, especially in the soils subjected to experimental groundwater-led saturation. Overall, the more C (from CO2 and CH4) was lost in drought-induced soils compared to field moist cores. Our results indicate that future drought events could have profound effects on the destabilization of protected C, especially in groundwater-fed soils. Our next steps focus on how to accurately capture drought-induced C destabilization mechanisms in earth system models.

Sediment-stabilizing and Destabilizing Ecoengineering Species from River to Estuary: the Case of the Scheldt System

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Selakovic, S.; Cozzoli, F.; Leuven, J.; Van Braeckel, A.; Speybroeck, J.; Kleinhans, M. G.; Bouma, T.

2017-12-01

Interactions between organisms and landscape forming processes play an important role in evolution of coastal landscapes. In particular, biota has a strong potential to interact with important geomorphological processes such as sediment dynamics. Although many studies worked towards quantifying the impact of different species groups on sediment dynamics, information has been gathered on an ad hoc base. Depending on species' traits and distribution, functional groups of ecoengineering species may have differential effects on sediment deposition and erosion. We hypothesize that the spatial distributions of sediment-stabilizing and destabilizing species across the channel and along the whole salinity gradient of an estuary partly determine the planform shape and channel-shoal morphology of estuaries. To test this hypothesis, we analyze vegetation and macrobenthic data taking the Scheldt river-estuarine continuum as model ecosystem. We identify species traits with important effects on sediment dynamics and use them to form functional groups. By using linearized mixed modelling, we are able to accurately describe the distributions of the different functional groups. We observe a clear distinction of dominant ecosystem engineering functional groups and their potential effects on the sediment in the river-estuarine continuum. The first results of longitudinal cross section show the highest effects of stabilizing plant species in riverine and sediment bioturbators in weak polyhaline part of continuum. The distribution of functional groups in transverse cross sections shows dominant stabilizing effect in supratidal zone compared to dominant destabilizing effect in the lower intertidal zone. This analysis offers a new and more general conceptualization of distributions of sediment stabilizing and destabilizing functional groups and their potential impacts on sediment dynamics, shoal patterns, and planform shapes in river-estuarine continuum. We intend to test this in future

Experimental study of smectite interaction with metal iron at low temperature: 1. Smectite destabilization.

OpenAIRE

Lantenois , Sébastien; Lanson , Bruno; Muller , Fabrice; Bauer , Andreas; Jullien , Michel; Plançon , Alain

2005-01-01

Interaction between metal Fe and a variety of natural and synthetic smectite samples with contrasting crystal chemistry was studied by scanning electron microscopy and X-ray diffraction from experiments conducted at 80°C. These experiments demonstrate an important reactivity contrast as a function of smectite crystal chemistry. An XRD method involving the use of an internal standard allowed quantification of the relative proportion of smectite destabilized as a function of initial pH conditio...

Positive Selection or Free to Vary? Assessing the Functional Significance of Sequence Change Using Molecular Dynamics.

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Jane R Allison

Full Text Available Evolutionary arms races between pathogens and their hosts may be manifested as selection for rapid evolutionary change of key genes, and are sometimes detectable through sequence-level analyses. In the case of protein-coding genes, such analyses frequently predict that specific codons are under positive selection. However, detecting positive selection can be non-trivial, and false positive predictions are a common concern in such analyses. It is therefore helpful to place such predictions within a structural and functional context. Here, we focus on the p19 protein from tombusviruses. P19 is a homodimer that sequesters siRNAs, thereby preventing the host RNAi machinery from shutting down viral infection. Sequence analysis of the p19 gene is complicated by the fact that it is constrained at the sequence level by overprinting of a viral movement protein gene. Using homology modeling, in silico mutation and molecular dynamics simulations, we assess how non-synonymous changes to two residues involved in forming the dimer interface-one invariant, and one predicted to be under positive selection-impact molecular function. Interestingly, we find that both observed variation and potential variation (where a non-synonymous change to p19 would be synonymous for the overprinted movement protein does not significantly impact protein structure or RNA binding. Consequently, while several methods identify residues at the dimer interface as being under positive selection, MD results suggest they are functionally indistinguishable from a site that is free to vary. Our analyses serve as a caveat to using sequence-level analyses in isolation to detect and assess positive selection, and emphasize the importance of also accounting for how non-synonymous changes impact structure and function.

Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection.

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Cornelia Di Gaetano

Full Text Available The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5 when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

Prediction of Genes Related to Positive Selection Using Whole-Genome Resequencing in Three Commercial Pig Breeds

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HyoYoung Kim

2015-12-01

Full Text Available Selective sweep can cause genetic differentiation across populations, which allows for the identification of possible causative regions/genes underlying important traits. The pig has experienced a long history of allele frequency changes through artificial selection in the domestication process. We obtained an average of 329,482,871 sequence reads for 24 pigs from three pig breeds: Yorkshire (n = 5, Landrace (n = 13, and Duroc (n = 6. An average read depth of 11.7 was obtained using whole-genome resequencing on an Illumina HiSeq2000 platform. In this study, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio tests were implemented to detect genes experiencing positive selection for the genome-wide resequencing data generated from three commercial pig breeds. In our results, 26, 7, and 14 genes from Yorkshire, Landrace, and Duroc, respectively were detected by two kinds of statistical tests. Significant evidence for positive selection was identified on genes ST6GALNAC2 and EPHX1 in Yorkshire, PARK2 in Landrace, and BMP6, SLA-DQA1, and PRKG1 in Duroc.These genes are reportedly relevant to lactation, reproduction, meat quality, and growth traits. To understand how these single nucleotide polymorphisms (SNPs related positive selection affect protein function, we analyzed the effect of non-synonymous SNPs. Three SNPs (rs324509622, rs80931851, and rs80937718 in the SLA-DQA1 gene were significant in the enrichment tests, indicating strong evidence for positive selection in Duroc. Our analyses identified genes under positive selection for lactation, reproduction, and meat-quality and growth traits in Yorkshire, Landrace, and Duroc, respectively.

NMR studies on the mechanism of structural destabilization of the globular proteins and DNA by aliphatic alcohols

International Nuclear Information System (INIS)

Lubas, B.; Witman, B.; Wieniewska, T.; Soltysik, M.

1977-01-01

The concept that the mechanism of structural destabilization of the biologically active macromolecules by typical denaturing agents should find a reflection in the NMR spectra of the denaturants themselves has been followed by proton NMR for some aliphatic alcohols in the system containing the serum albumin of DNA. (author)

Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance.

Science.gov (United States)

Taye, Mengistie; Lee, Wonseok; Caetano-Anolles, Kelsey; Dessie, Tadelle; Hanotte, Olivier; Mwai, Okeyo Ally; Kemp, Stephen; Cho, Seoae; Oh, Sung Jong; Lee, Hak-Kyo; Kim, Heebal

2017-12-01

As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH) and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41 biological process terms and six Kyoto Encyclopedia of Genes and Genomes pathways. Several genes and pathways were found to be involved in oxidative stress response, osmotic stress response, heat shock response, hair and skin properties, sweat gland development and sweating, feed intake and metabolism, and reproduction functions. The genes and pathways identified directly or indirectly contribute to the superior heat tolerance mechanisms in African cattle populations. The result will improve our understanding of the biological mechanisms of heat tolerance in African cattle breeds and opens an avenue for further study. © 2017 Japanese Society of Animal Science.

A charged residue at the subunit interface of PCNA promotes trimer formation by destabilizing alternate subunit interactions

International Nuclear Information System (INIS)

Freudenthal, Bret D.; Gakhar, Lokesh; Ramaswamy, S.; Washington, M. Todd

2009-01-01

Eukaryotic proliferating cell nuclear antigen (PCNA), an essential accessory factor in DNA replication and repair, is a ring-shaped homotrimer. A novel nontrimeric structure of E113G-mutant PCNA protein is reported, which shows that this protein forms alternate subunit interactions. It is concluded that the charged side chain of Glu113 promotes normal trimer formation by destabilizing these alternate subunit interactions. Eukaryotic proliferating cell nuclear antigen (PCNA) is an essential replication accessory factor that interacts with a variety of proteins involved in DNA replication and repair. Each monomer of PCNA has an N-terminal domain A and a C-terminal domain B. In the structure of the wild-type PCNA protein, domain A of one monomer interacts with domain B of a neighboring monomer to form a ring-shaped trimer. Glu113 is a conserved residue at the subunit interface in domain A. Two distinct X-ray crystal structures have been determined of a mutant form of PCNA with a substitution at this position (E113G) that has previously been studied because of its effect on translesion synthesis. The first structure was the expected ring-shaped trimer. The second structure was an unanticipated nontrimeric form of the protein. In this nontrimeric form, domain A of one PCNA monomer interacts with domain A of a neighboring monomer, while domain B of this monomer interacts with domain B of a different neighboring monomer. The B–B interface is stabilized by an antiparallel β-sheet and appears to be structurally similar to the A–B interface observed in the trimeric form of PCNA. The A–A interface, in contrast, is primarily stabilized by hydrophobic interactions. Because the E113G substitution is located on this hydrophobic surface, the A–A interface should be less favorable in the case of the wild-type protein. This suggests that the side chain of Glu113 promotes trimer formation by destabilizing these possible alternate subunit interactions

CRITICAL HEIGHT FOR THE DESTABILIZATION OF SOLAR PROMINENCES: STATISTICAL RESULTS FROM STEREO OBSERVATIONS

Energy Technology Data Exchange (ETDEWEB)

Liu Kai; Wang Yuming; Wang Shui; Shen Chenglong, E-mail: ymwang@ustc.edu.cn [CAS Key Laboratory of Geospace Environment, Department of Geophysics and Planetary Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China)

2012-01-10

At which height is a prominence inclined to be unstable, or where is the most probable critical height for the prominence destabilization? This question was statistically studied based on 362 solar limb prominences well recognized by Solar Limb Prominence Catcher and Tracker from 2007 April to the end of 2009. We found that there are about 71% disrupted prominences (DPs), among which about 42% of them did not erupt successfully and about 89% of them experienced a sudden destabilization process. After a comprehensive analysis of the DPs, we discovered the following: (1) Most DPs become unstable at a height of 0.06-0.14 R{sub Sun} from the solar surface, and there are two most probable critical heights at which a prominence is very likely to become unstable, the first one is 0.13 R{sub Sun} and the second one is 0.19 R{sub Sun }. (2) An upper limit for the erupting velocity of eruptive prominences (EPs) exists, which decreases following a power law with increasing height and mass; accordingly, the kinetic energy of EPs has an upper limit too, which decreases as the critical height increases. (3) Stable prominences are generally longer and heavier than DPs, and not higher than 0.4 R{sub Sun }. (4) About 62% of the EPs were associated with coronal mass ejections (CMEs); but there is no difference in apparent properties between EPs associated with CMEs and those that are not.

CRITICAL HEIGHT FOR THE DESTABILIZATION OF SOLAR PROMINENCES: STATISTICAL RESULTS FROM STEREO OBSERVATIONS

International Nuclear Information System (INIS)

Liu Kai; Wang Yuming; Wang Shui; Shen Chenglong

2012-01-01

At which height is a prominence inclined to be unstable, or where is the most probable critical height for the prominence destabilization? This question was statistically studied based on 362 solar limb prominences well recognized by Solar Limb Prominence Catcher and Tracker from 2007 April to the end of 2009. We found that there are about 71% disrupted prominences (DPs), among which about 42% of them did not erupt successfully and about 89% of them experienced a sudden destabilization process. After a comprehensive analysis of the DPs, we discovered the following: (1) Most DPs become unstable at a height of 0.06-0.14 R ☉ from the solar surface, and there are two most probable critical heights at which a prominence is very likely to become unstable, the first one is 0.13 R ☉ and the second one is 0.19 R ☉ . (2) An upper limit for the erupting velocity of eruptive prominences (EPs) exists, which decreases following a power law with increasing height and mass; accordingly, the kinetic energy of EPs has an upper limit too, which decreases as the critical height increases. (3) Stable prominences are generally longer and heavier than DPs, and not higher than 0.4 R ☉ . (4) About 62% of the EPs were associated with coronal mass ejections (CMEs); but there is no difference in apparent properties between EPs associated with CMEs and those that are not.

Ancient and recent positive selection transformed opioid cis-regulation in humans.

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Matthew V Rockman

2005-12-01

Full Text Available Changes in the cis-regulation of neural genes likely contributed to the evolution of our species' unique attributes, but evidence of a role for natural selection has been lacking. We found that positive natural selection altered the cis-regulation of human prodynorphin, the precursor molecule for a suite of endogenous opioids and neuropeptides with critical roles in regulating perception, behavior, and memory. Independent lines of phylogenetic and population genetic evidence support a history of selective sweeps driving the evolution of the human prodynorphin promoter. In experimental assays of chimpanzee-human hybrid promoters, the selected sequence increases transcriptional inducibility. The evidence for a change in the response of the brain's natural opioids to inductive stimuli points to potential human-specific characteristics favored during evolution. In addition, the pattern of linked nucleotide and microsatellite variation among and within modern human populations suggests that recent selection, subsequent to the fixation of the human-specific mutations and the peopling of the globe, has favored different prodynorphin cis-regulatory alleles in different parts of the world.

Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

Science.gov (United States)

Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

2006-05-01

The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

Widespread Positive Selection Drives Differentiation of Centromeric Proteins in the Drosophila melanogaster subgroup.

Science.gov (United States)

Beck, Emily A; Llopart, Ana

2015-11-25

Rapid evolution of centromeric satellite repeats is thought to cause compensatory amino acid evolution in interacting centromere-associated kinetochore proteins. Cid, a protein that mediates kinetochore/centromere interactions, displays particularly high amino acid turnover. Rapid evolution of both Cid and centromeric satellite repeats led us to hypothesize that the apparent compensatory evolution may extend to interacting partners in the Condensin I complex (i.e., SMC2, SMC4, Cap-H, Cap-D2, and Cap-G) and HP1s. Missense mutations in these proteins often result in improper centromere formation and aberrant chromosome segregation, thus selection for maintained function and coevolution among proteins of the complex is likely strong. Here, we report evidence of rapid evolution and recurrent positive selection in seven centromere-associated proteins in species of the Drosophila melanogaster subgroup, and further postulate that positive selection on these proteins could be a result of centromere drive and compensatory changes, with kinetochore proteins competing for optimal spindle attachment.

Positive-negative-selection-mediated gene targeting in rice

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Zenpei eShimatani

2015-01-01

Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

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Daniele Fanale

2015-01-01

Full Text Available Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.

 Molecular evolution and positive selection of the symbiotic gene NORK in Medicago truncatula

DEFF Research Database (Denmark)

De Mita, Stephane; Santoni, Sylvain; Hochu, Isabelle

2006-01-01

 Understanding the selective constraints of partner specificity in mutually beneficial symbiosis is a significant, yet largely unexplored, prospect of evolutionary biology. These selective constraints can be explored through the study of nucleotide polymorphism at loci controlling specificity...... domain of the protein, evolved under the regime of positive selection. Further research should focus on the rate and direction of molecular coevolution between microorganisms' signaling molecules and legumes' receptors....

Systematic hybrid LOH: a new method to reduce false positives and negatives during screening of yeast gene deletion libraries

DEFF Research Database (Denmark)

Alvaro, D.; Sunjevaric, I.; Reid, R. J.

2006-01-01

We have developed a new method, systematic hybrid loss of heterozygosity, to facilitate genomic screens utilizing the yeast gene deletion library. Screening is performed using hybrid diploid strains produced through mating the library haploids with strains from a different genetic background......, to minimize the contribution of unpredicted recessive genetic factors present in the individual library strains. We utilize a set of strains where each contains a conditional centromere construct on one of the 16 yeast chromosomes that allows the destabilization and selectable loss of that chromosome. After...... complementation of any spurious recessive mutations in the library strain, facilitating attribution of the observed phenotype to the documented gene deletion and dramatically reducing false positive results commonly obtained in library screens. The systematic hybrid LOH method can be applied to virtually any...

Asymmetric membranes for destabilization of oil droplets in produced water from alkaline-surfactant-polymer (ASP) flooding

Science.gov (United States)

Ramlee, Azierah; Chiam, Chel-Ken; Sarbatly, Rosalam

2018-05-01

This work presents a study of destabilization of oil droplets in the produced water from alkaline-surfactant-polymer (ASP) flooding by using four types of laboratory-fabricated polyvinylidene fluoride (PVDF) membranes. The PVDF membranes were fabricated via immersion precipitation method with ethanol (0 - 30 %, v/v) as the coagulant. The membranes with the effective area of 17.35 cm2 were tested with synthesized ASP solution as the feed in cross-flow microfiltration process. The ASP feed solution initially contained the oil droplets with radius ranged from 40 to 100 nm and the mean radius was 61 nm. Results have shown that the concentration of the ethanol in the coagulation bath affects the formation of the membrane structure and the corresponding porosity, while no significance influence on the membrane thickness. Coalescence of the oil droplets was occurred when the ASP solution permeated through the asymmetric PVDF membranes. Through the coalescence process, the oil droplets were destabilized where the radius of the oil droplets in the permeates increased to 1.5-4 µm with the corresponding mean radius ranged from 2.4 to 2.7 µm.

Positive and purifying selection influence the evolution of doublesex in the Anastrepha fraterculus species group.

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Iderval S Sobrinho

Full Text Available The gene doublesex (dsx is considered to be under strong selective constraint along its evolutionary history because of its central role in somatic sex differentiation in insects. However, previous studies of dsx used global estimates of evolutionary rates to investigate its molecular evolution, which potentially miss signals of adaptive changes in generally conserved genes. In this work, we investigated the molecular evolution of dsx in the Anastrepha fraterculus species group (Diptera, Tephritidae, and test the hypothesis that this gene evolved solely by purifying selection using divergence-based and population-based methods. In the first approach, we compared sequences from Anastrepha and other Tephritidae with other Muscomorpha species, analyzed variation in nonsynonymous to synonymous rate ratios (dN/dS in the Tephritidae, and investigated radical and conservative changes in amino acid physicochemical properties. We show a general selective constraint on dsx, but with signs of positive selection mainly in the common region. Such changes were localized in alpha-helices previously reported to be involved in dimer formation in the OD2 domain and near the C-terminal of the OD1 domain. In the population-based approach, we amplified a region of 540 bp that spanned almost all of the region common to both sexes from 32 different sites in Brazil. We investigated patterns of selection using neutrality tests based on the frequency spectrum and locations of synonymous and nonsynonymous mutations in a haplotype network. As in the divergence-based approach, these analyses showed that dsx has evolved under an overall selective constraint, but with some events of positive selection. In contrast to previous studies, our analyses indicate that even though dsx has indeed evolved as a conserved gene, the common region of dsx has also experienced bouts of positive selection, perhaps driven by sexual selection, during its evolution.

Improved methods in Agrobacterium-mediated transformation of almond using positive (mannose/pmi) or negative (kanamycin resistance) selection-based protocols.

Science.gov (United States)

Ramesh, Sunita A; Kaiser, Brent N; Franks, Tricia; Collins, Graham; Sedgley, Margaret

2006-08-01

A protocol for Agrobacterium-mediated transformation with either kanamycin or mannose selection was developed for leaf explants of the cultivar Prunus dulcis cv. Ne Plus Ultra. Regenerating shoots were selected on medium containing 15 muM kanamycin (negative selection), while in the positive selection strategy, shoots were selected on 2.5 g/l mannose supplemented with 15 g/l sucrose. Transformation efficiencies based on PCR analysis of individual putative transformed shoots from independent lines relative to the initial numbers of leaf explants tested were 5.6% for kanamycin/nptII and 6.8% for mannose/pmi selection, respectively. Southern blot analysis on six randomly chosen PCR-positive shoots confirmed the presence of the nptII transgene in each, and five randomly chosen lines identified to contain the pmi transgene by PCR showed positive hybridisation to a pmi DNA probe. The positive (mannose/pmi) and the negative (kanamycin) selection protocols used in this study have greatly improved transformation efficiency in almond, which were confirmed with PCR and Southern blot. This study also demonstrates that in almond the mannose/pmi selection protocol is appropriate and can result in higher transformation efficiencies over that of kanamycin/nptII selection protocols.

S-Nitrosation destabilizes glutathione transferase P1-1.

Science.gov (United States)

Balchin, David; Stoychev, Stoyan H; Dirr, Heini W

2013-12-23

Protein S-nitrosation is a post-translational modification that regulates the function of more than 500 human proteins. Despite its apparent physiological significance, S-nitrosation is poorly understood at a molecular level. Here, we investigated the effect of S-nitrosation on the activity, structure, stability, and dynamics of human glutathione transferase P1-1 (GSTP1-1), an important detoxification enzyme ubiquitous in aerobes. S-Nitrosation at Cys47 and Cys101 reduces the activity of the enzyme by 94%. Circular dichroism spectroscopy, acrylamide quenching, and amide hydrogen-deuterium exchange mass spectrometry experiments indicate that the loss of activity is caused by the introduction of local disorder at the active site of GSTP1-1. Furthermore, the modification destabilizes domain 1 of GSTP1-1 against denaturation, smoothing the unfolding energy landscape of the protein and introducing a refolding defect. In contrast, S-nitrosation at Cys101 alone introduces a refolding defect in domain 1 but compensates by stabilizing the domain kinetically. These data elucidate the physical basis for the regulation of GSTP1-1 by S-nitrosation and provide general insight into the consequences of S-nitrosation on protein stability and dynamics.

The positive dimension of the conflict in news interviews

Directory of Open Access Journals (Sweden)

Thales Vilela Lelo

2012-04-01

Full Text Available This paper reflects about a possible positive dimension of the conflict, starting with an exhibition that addresses the world of journalism interviews. Using the positivity attributed to the conflict in the theorizing of Georg Simmel as a complement to the dialogical movement developed in Martin Buber theorizations, will perform the analysis of an interview conducted in the Globo News guided by the discrepancy between the interviewer/interviewee. From this point, the concepts are articulated with an emphasis on a pragmatic framework, so that it discusses the conflict as an element with potential to promote destabilization on conventional frames of journalism, managing the public and inviting him to debate about a specific problematic field.

Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

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Erik Corona

Full Text Available Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS, providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

De novo transcriptome assembly and positive selection analysis of an individual deep-sea fish.

Science.gov (United States)

Lan, Yi; Sun, Jin; Xu, Ting; Chen, Chong; Tian, Renmao; Qiu, Jian-Wen; Qian, Pei-Yuan

2018-05-24

High hydrostatic pressure and low temperatures make the deep sea a harsh environment for life forms. Actin organization and microtubules assembly, which are essential for intracellular transport and cell motility, can be disrupted by high hydrostatic pressure. High hydrostatic pressure can also damage DNA. Nucleic acids exposed to low temperatures can form secondary structures that hinder genetic information processing. To study how deep-sea creatures adapt to such a hostile environment, one of the most straightforward ways is to sequence and compare their genes with those of their shallow-water relatives. We captured an individual of the fish species Aldrovandia affinis, which is a typical deep-sea inhabitant, from the Okinawa Trough at a depth of 1550 m using a remotely operated vehicle (ROV). We sequenced its transcriptome and analyzed its molecular adaptation. We obtained 27,633 protein coding sequences using an Illumina platform and compared them with those of several shallow-water fish species. Analysis of 4918 single-copy orthologs identified 138 positively selected genes in A. affinis, including genes involved in microtubule regulation. Particularly, functional domains related to cold shock as well as DNA repair are exposed to positive selection pressure in both deep-sea fish and hadal amphipod. Overall, we have identified a set of positively selected genes related to cytoskeleton structures, DNA repair and genetic information processing, which shed light on molecular adaptation to the deep sea. These results suggest that amino acid substitutions of these positively selected genes may contribute crucially to the adaptation of deep-sea animals. Additionally, we provide a high-quality transcriptome of a deep-sea fish for future deep-sea studies.

Whole-gene positive selection, elevated synonymous substitution rates, duplication, and indel evolution of the chloroplast clpP1 gene.

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Per Erixon

Full Text Available BACKGROUND: Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. METHODOLOGY/PRINCIPLE FINDINGS: We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family. Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. CONCLUSIONS/SIGNIFICANCE: We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

DEFF Research Database (Denmark)

Dasmeh, Pouria; Kepp, Kasper Planeta

2017-01-01

Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers...... and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging....... of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million...

Growth of non-Campylobacter, oxidase-positive bacteria on selective Campylobacter agar.

OpenAIRE

Moskowitz, L B; Chester, B

1982-01-01

A total of 67 oxidase-positive, gram-negative bacteria were tested for growth on selective Campylobacter agar (Blaser formulation, BBL Microbiology Systems, Cockeysville, Md.) at 42 degrees C under microaerophilic conditions. Although the growth of most of these bacteria was prevented, all strains of Achromobacter xylosoxidans, Pseudomonas aeruginosa, Pseudomonas putrefaciens, Pseudomonas alcaligenes, and Pseudomonas pseudoalcaligenes grew as well as Campylobacter fetus subsp. jejuni.

Quasi-linear analysis of the extraordinary electron wave destabilized by runaway electrons

Energy Technology Data Exchange (ETDEWEB)

Pokol, G. I.; Kómár, A.; Budai, A. [Department of Nuclear Techniques, Budapest University of Technology and Economics, Budapest (Hungary); Stahl, A.; Fülöp, T. [Department of Applied Physics, Chalmers University of Technology, Göteborg (Sweden)

2014-10-15

Runaway electrons with strongly anisotropic distributions present in post-disruption tokamak plasmas can destabilize the extraordinary electron (EXEL) wave. The present work investigates the dynamics of the quasi-linear evolution of the EXEL instability for a range of different plasma parameters using a model runaway distribution function valid for highly relativistic runaway electron beams produced primarily by the avalanche process. Simulations show a rapid pitch-angle scattering of the runaway electrons in the high energy tail on the 100–1000 μs time scale. Due to the wave-particle interaction, a modification to the synchrotron radiation spectrum emitted by the runaway electron population is foreseen, exposing a possible experimental detection method for such an interaction.

Evidence of positive selection associated with placental loss in tiger sharks.

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Swift, Dominic G; Dunning, Luke T; Igea, Javier; Brooks, Edward J; Jones, Catherine S; Noble, Leslie R; Ciezarek, Adam; Humble, Emily; Savolainen, Vincent

2016-06-14

All vertebrates initially feed their offspring using yolk reserves. In some live-bearing species these yolk reserves may be supplemented with extra nutrition via a placenta. Sharks belonging to the Carcharhinidae family are all live-bearing, and with the exception of the tiger shark (Galeocerdo cuvier), develop placental connections after exhausting yolk reserves. Phylogenetic relationships suggest the lack of placenta in tiger sharks is due to secondary loss. This represents a dramatic shift in reproductive strategy, and is likely to have left a molecular footprint of positive selection within the genome. We sequenced the transcriptome of the tiger shark and eight other live-bearing shark species. From this data we constructed a time-calibrated phylogenetic tree estimating the tiger shark lineage diverged from the placental carcharhinids approximately 94 million years ago. Along the tiger shark lineage, we identified five genes exhibiting a signature of positive selection. Four of these genes have functions likely associated with brain development (YWHAE and ARL6IP5) and sexual reproduction (VAMP4 and TCTEX1D2). Our results indicate the loss of placenta in tiger sharks may be associated with subsequent adaptive changes in brain development and sperm production.

The mass media destabilizes the cultural homogenous regime in Axelrod's model

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Peres, Lucas R.; Fontanari, José F.

2010-02-01

An important feature of Axelrod's model for culture dissemination or social influence is the emergence of many multicultural absorbing states, despite the fact that the local rules that specify the agents interactions are explicitly designed to decrease the cultural differences between agents. Here we re-examine the problem of introducing an external, global interaction—the mass media—in the rules of Axelrod's model: in addition to their nearest neighbors, each agent has a certain probability p to interact with a virtual neighbor whose cultural features are fixed from the outset. Most surprisingly, this apparently homogenizing effect actually increases the cultural diversity of the population. We show that, contrary to previous claims in the literature, even a vanishingly small value of p is sufficient to destabilize the homogeneous regime for very large lattice sizes.

The mass media destabilizes the cultural homogenous regime in Axelrod's model

International Nuclear Information System (INIS)

Peres, Lucas R; Fontanari, Jose F

2010-01-01

An important feature of Axelrod's model for culture dissemination or social influence is the emergence of many multicultural absorbing states, despite the fact that the local rules that specify the agents interactions are explicitly designed to decrease the cultural differences between agents. Here we re-examine the problem of introducing an external, global interaction-the mass media-in the rules of Axelrod's model: in addition to their nearest neighbors, each agent has a certain probability p to interact with a virtual neighbor whose cultural features are fixed from the outset. Most surprisingly, this apparently homogenizing effect actually increases the cultural diversity of the population. We show that, contrary to previous claims in the literature, even a vanishingly small value of p is sufficient to destabilize the homogeneous regime for very large lattice sizes.

Evidence of recombination and positive selection in cetacean papillomaviruses

International Nuclear Information System (INIS)

Robles-Sikisaka, Refugio; Rivera, Rebecca; Nollens, Hendrik H.; St Leger, Judy; Durden, Wendy N.; Stolen, Megan; Burchell, Jennifer; Wellehan, James F.X.

2012-01-01

Papillomaviruses (PVs) are small DNA viruses that have been associated with increased epithelial proliferation. Over one hundred PV types have been identified in humans; however, only three have been identified in bottlenose dolphins (Tursiops truncatus) to date. Using rolling circle amplification and degenerate PCR, we identified four novel PV genomes of bottlenose dolphins. TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was identified in normal genital mucosa. Bayesian analysis of the full-length L1 genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the E1 gene did not distinguish these genera, implying that these genes may not share a common history, consistent with recombination. Recombination analyses identified several probable events. Signals of positive selection were found mostly in the E1 and E2 genes. Recombination and diversifying selection pressures constitute important driving forces of cetacean PV evolution.

Evidence of recombination and positive selection in cetacean papillomaviruses

Energy Technology Data Exchange (ETDEWEB)

Robles-Sikisaka, Refugio, E-mail: refugio.robles1@gmail.com [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); Rivera, Rebecca, E-mail: RRivera@hswri.org [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); Nollens, Hendrik H., E-mail: Hendrik.Nollens@SeaWorld.com [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); College of Veterinary Medicine, University of Florida, PO Box 110885, Gainesville, FL 32611 (United States); SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); St Leger, Judy, E-mail: Judy.St.Leger@SeaWorld.com [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Durden, Wendy N., E-mail: WNoke@hswri.org [Hubbs-SeaWorld Research Institute, 3830 South Highway A1A 4-181, Melbourne Beach, FL 32951 (United States); Stolen, Megan, E-mail: MStolen@hswri.org [Hubbs-SeaWorld Research Institute, 3830 South Highway A1A 4-181, Melbourne Beach, FL 32951 (United States); Burchell, Jennifer, E-mail: JBurchell@hswri.org [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); Wellehan, James F.X., E-mail: WellehanJ@ufl.edu [College of Veterinary Medicine, University of Florida, PO Box 110885, Gainesville, FL 32611 (United States)

2012-06-05

Papillomaviruses (PVs) are small DNA viruses that have been associated with increased epithelial proliferation. Over one hundred PV types have been identified in humans; however, only three have been identified in bottlenose dolphins (Tursiops truncatus) to date. Using rolling circle amplification and degenerate PCR, we identified four novel PV genomes of bottlenose dolphins. TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was identified in normal genital mucosa. Bayesian analysis of the full-length L1 genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the E1 gene did not distinguish these genera, implying that these genes may not share a common history, consistent with recombination. Recombination analyses identified several probable events. Signals of positive selection were found mostly in the E1 and E2 genes. Recombination and diversifying selection pressures constitute important driving forces of cetacean PV evolution.

Destabilizing effect of alpha particles in a Maxwellian plasma

International Nuclear Information System (INIS)

Wang, M.Y.

1976-01-01

Various plasma waves which are possibly excited by MeV alphas have been investigated. For a delta birth distribution it is found that: a) The right-circularly polarized Alfven wave can be excited. Its growth rate is linearly proportional to the α-particle density. b) The drift Alfven wave is stable against α-particles. c) For a uniform temperature, the plasma wave spectrum changes from three branches with n/sub α/ = 0 to four branches for n/sub α/ not equal to 0 case. d) α-particles can destabilize the ion drift acoustic wave even with uniform temperature. However, the ion acoustic wave appears to be stable against fusion products in a fusion grade plasma. e) If their effect on the background plasma spectrum is neglected, α-particles can excite the electromagnetic cyclotron wave in a range of harmonics (band structure). The growth rate is proportional to the square root of α-particle density. f) If the effect of α-particle on the plasma spectrum is included, we find that electromagnetic cyclotron wave is stable

Red Queen Processes Drive Positive Selection on Major Histocompatibility Complex (MHC Genes.

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Maciej Jan Ejsmond

2015-11-01

Full Text Available Major Histocompatibility Complex (MHC genes code for proteins involved in the incitation of the adaptive immune response in vertebrates, which is achieved through binding oligopeptides (antigens of pathogenic origin. Across vertebrate species, substitutions of amino acids at sites responsible for the specificity of antigen binding (ABS are positively selected. This is attributed to pathogen-driven balancing selection, which is also thought to maintain the high polymorphism of MHC genes, and to cause the sharing of allelic lineages between species. However, the nature of this selection remains controversial. We used individual-based computer simulations to investigate the roles of two phenomena capable of maintaining MHC polymorphism: heterozygote advantage and host-pathogen arms race (Red Queen process. Our simulations revealed that levels of MHC polymorphism were high and driven mostly by the Red Queen process at a high pathogen mutation rate, but were low and driven mostly by heterozygote advantage when the pathogen mutation rate was low. We found that novel mutations at ABSs are strongly favored by the Red Queen process, but not by heterozygote advantage, regardless of the pathogen mutation rate. However, while the strong advantage of novel alleles increased the allele turnover rate, under a high pathogen mutation rate, allelic lineages persisted for a comparable length of time under Red Queen and under heterozygote advantage. Thus, when pathogens evolve quickly, the Red Queen is capable of explaining both positive selection and long coalescence times, but the tension between the novel allele advantage and persistence of alleles deserves further investigation.

Detecting Signatures of Positive Selection along Defined Branches of a Population Tree Using LSD.

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Librado, Pablo; Orlando, Ludovic

2018-06-01

Identifying the genomic basis underlying local adaptation is paramount to evolutionary biology, and bears many applications in the fields of conservation biology, crop, and animal breeding, as well as personalized medicine. Although many approaches have been developed to detect signatures of positive selection within single populations and population pairs, the increasing wealth of high-throughput sequencing data requires improved methods capable of handling multiple, and ideally large number of, populations in a single analysis. In this study, we introduce LSD (levels of exclusively shared differences), a fast and flexible framework to perform genome-wide selection scans, along the internal and external branches of a given population tree. We use forward simulations to demonstrate that LSD can identify branches targeted by positive selection with remarkable sensitivity and specificity. We illustrate a range of potential applications by analyzing data from the 1000 Genomes Project and uncover a list of adaptive candidates accompanying the expansion of anatomically modern humans out of Africa and their spread to Europe.

Positive Selection Driving Cytoplasmic Genome Evolution of the Medicinally Important Ginseng Plant Genus Panax.

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Jiang, Peng; Shi, Feng-Xue; Li, Ming-Rui; Liu, Bao; Wen, Jun; Xiao, Hong-Xing; Li, Lin-Feng

2018-01-01

Panax L. (the ginseng genus) is a shade-demanding group within the family Araliaceae and all of its species are of crucial significance in traditional Chinese medicine. Phylogenetic and biogeographic analyses demonstrated that two rounds of whole genome duplications accompanying with geographic and ecological isolations promoted the diversification of Panax species. However, contributions of the cytoplasmic genomes to the adaptive evolution of Panax species remained largely uninvestigated. In this study, we sequenced the chloroplast and mitochondrial genomes of 11 accessions belonging to seven Panax species. Our results show that heterogeneity in nucleotide substitution rate is abundant in both of the two cytoplasmic genomes, with the mitochondrial genome possessing more variants at the total level but the chloroplast showing higher sequence polymorphisms at the genic regions. Genome-wide scanning of positive selection identified five and 12 genes from the chloroplast and mitochondrial genomes, respectively. Functional analyses further revealed that these selected genes play important roles in plant development, cellular metabolism and adaptation. We therefore conclude that positive selection might be one of the potential evolutionary forces that shaped nucleotide variation pattern of these Panax species. In particular, the mitochondrial genes evolved under stronger selective pressure compared to the chloroplast genes.

The cystic-fibrosis-associated ΔF508 mutation confers post-transcriptional destabilization on the C. elegans ABC transporter PGP-3

Directory of Open Access Journals (Sweden)

Liping He

2012-11-01

Membrane proteins make up ∼30% of the proteome. During the early stages of maturation, this class of proteins can experience localized misfolding in distinct cellular compartments, such as the cytoplasm, endoplasmic reticulum (ER lumen and ER membrane. ER quality control (ERQC mechanisms monitor folding and determine whether a membrane protein is appropriately folded or is misfolded and warrants degradation. ERQC plays crucial roles in human diseases, such as cystic fibrosis, in which deletion of a single amino acid (F508 results in the misfolding and degradation of the cystic fibrosis transmembrane conductance regulator (CFTR Cl– channel. We introduced the ΔF508 mutation into Caenorhabditis elegans PGP-3, a 12-transmembrane ABC transporter with 15% identity to CFTR. When expressed in intestinal epithelial cells, PGP-3wt was stable and efficiently trafficked to the apical plasma membrane through a COPII-dependent mechanism. However, PGP-3ΔF508 was post-transcriptionally destabilized, resulting in reduced total and apical membrane protein levels. Genetic or physiological activation of the osmotic stress response pathway, which causes accumulation of the chemical chaperone glycerol, stabilized PGP-3ΔF508. Efficient degradation of PGP-3ΔF508 required the function of several C. elegans ER-associated degradation (ERAD homologs, suggesting that destabilization occurs through an ERAD-type mechanism. Our studies show that the ΔF508 mutation causes post-transcriptional destabilization and degradation of PGP-3 in C. elegans epithelial cells. This model, combined with the power of C. elegans genetics, provides a new opportunity to genetically dissect metazoan ERQC.

Mode Selection Rules for a Two-Delay System with Positive and Negative Feedback Loops

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Takahashi, Kin'ya; Kobayashi, Taizo

2018-04-01

The mode selection rules for a two-delay system, which has negative feedback with a short delay time t1 and positive feedback with a long delay time t2, are studied numerically and theoretically. We find two types of mode selection rules depending on the strength of the negative feedback. When the strength of the negative feedback |α1| (α1 0), 2m + 1-th harmonic oscillation is well sustained in a neighborhood of t1/t2 = even/odd, i.e., relevant condition. In a neighborhood of the irrelevant condition given by t1/t2 = odd/even or t1/t2 = odd/odd, higher harmonic oscillations are observed. However, if |α1| is slightly less than α2, a different mode selection rule works, where the condition t1/t2 = odd/even is relevant and the conditions t1/t2 = odd/odd and t1/t2 = even/odd are irrelevant. These mode selection rules are different from the mode selection rule of the normal two-delay system with two positive feedback loops, where t1/t2 = odd/odd is relevant and the others are irrelevant. The two types of mode selection rules are induced by individually different mechanisms controlling the Hopf bifurcation, i.e., the Hopf bifurcation controlled by the "boosted bifurcation process" and by the "anomalous bifurcation process", which occur for |α1| below and above the threshold value αth, respectively.

Destabilization of Akt Promotes the Death of Myeloma Cell Lines

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Yanan Zhang

2014-01-01

Full Text Available Constitutive activation of Akt is believed to be an oncogenic signal in multiple myeloma and is associated with poor patient prognosis and resistance to available treatment. The stability of Akt proteins is regulated by phosphorylating the highly conserved turn motif (TM of these proteins and the chaperone protein HSP90. In this study we investigate the antitumor effects of inhibiting mTORC2 plus HSP90 in myeloma cell lines. We show that chronic exposure of cells to rapamycin can inhibit mTORC2 pathway, and AKT will be destabilized by administration of the HSP90 inhibitor 17-allylamino-geldanamycin (17-AAG. Finally, we show that the rapamycin synergizes with 17-AAG and inhibits myeloma cells growth and promotes cell death to a greater extent than either drug alone. Our studies provide a clinical rationale of use mTOR inhibitors and chaperone protein inhibitors in combination regimens for the treatment of human blood cancers.

Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation.

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Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

2017-05-23

The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA-DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA-DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs.

Changing folding and binding stability in a viral coat protein: a comparison between substitutions accessible through mutation and those fixed by natural selection.

Science.gov (United States)

Miller, Craig R; Lee, Kuo Hao; Wichman, Holly A; Ytreberg, F Marty

2014-01-01

Previous studies have shown that most random amino acid substitutions destabilize protein folding (i.e. increase the folding free energy). No analogous studies have been carried out for protein-protein binding. Here we use a structure-based model of the major coat protein in a simple virus, bacteriophage φX174, to estimate the free energy of folding of a single coat protein and binding of five coat proteins within a pentameric unit. We confirm and extend previous work in finding that most accessible substitutions destabilize both protein folding and protein-protein binding. We compare the pool of accessible substitutions with those observed among the φX174-like wild phage and in experimental evolution with φX174. We find that observed substitutions have smaller effects on stability than expected by chance. An analysis of adaptations at high temperatures suggests that selection favors either substitutions with no effect on stability or those that simultaneously stabilize protein folding and slightly destabilize protein binding. We speculate that these mutations might involve adjusting the rate of capsid assembly. At normal laboratory temperature there is little evidence of directional selection. Finally, we show that cumulative changes in stability are highly variable; sometimes they are well beyond the bounds of single substitution changes and sometimes they are not. The variation leads us to conclude that phenotype selection acts on more than just stability. Instances of larger cumulative stability change (never via a single substitution despite their availability) lead us to conclude that selection views stability at a local, not a global, level.

Selective bowel decontamination results in gram-positive translocation.

Science.gov (United States)

Jackson, R J; Smith, S D; Rowe, M I

1990-05-01

Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

Experimental study of the stabilization process of a non-premixed flame via the destabilization analysis of the blue ring flame

Energy Technology Data Exchange (ETDEWEB)

Pinguet, Guillaume; Escudie, Dany [Centre de Thermique de Lyon (CETHIL) UMR 5008 CNRS-INSA-UCBL, INSA de Lyon, 20 av. A. Einstein, 69621 Villeurbanne cedex (France)

2007-04-15

The flame stabilization phenomenon remains a crucial issue. The experimental study of flame stabilization behind a tulip-shaped flame-holder is addressed in this paper. The process leading to the transition between specific modes - the blue ring flame and the instable ring - of a non-premixed flame stabilized on a tulip-shaped bluff-body is detailed. The aim of this study is to provide an accurate description of the destabilization of specific combustion modes, which enables a further understanding of the entire stabilization mechanism. The aerodynamic and mixing fields are described by laser Doppler anemometry and concentration measurements by sampling probe respectively. The behaviour of shear layers developing at the wake and jet boundaries are characterized by means of a spectral analysis of the fluctuating radial velocity. Results show that the destabilization process is related to the intensification of hot gas recirculation, inducing an upheaval of the dynamical condition of stabilization and a transition of mixing phenomena. (author)

Bayes Empirical Bayes Inference of Amino Acid Sites Under Positive Selection

DEFF Research Database (Denmark)

Yang, Ziheng; Wong, Wendy Shuk Wan; Nielsen, Rasmus

2005-01-01

, with > 1 indicating positive selection. Statistical distributions are used to model the variation in among sites, allowing a subset of sites to have > 1 while the rest of the sequence may be under purifying selection with ... probabilities that a site comes from the site class with > 1. Current implementations, however, use the naive EB (NEB) approach and fail to account for sampling errors in maximum likelihood estimates of model parameters, such as the proportions and ratios for the site classes. In small data sets lacking...... information, this approach may lead to unreliable posterior probability calculations. In this paper, we develop a Bayes empirical Bayes (BEB) approach to the problem, which assigns a prior to the model parameters and integrates over their uncertainties. We compare the new and old methods on real and simulated...

Transcriptome-based phylogeny of endemic Lake Baikal amphipod species flock: fast speciation accompanied by frequent episodes of positive selection.

Science.gov (United States)

Naumenko, Sergey A; Logacheva, Maria D; Popova, Nina V; Klepikova, Anna V; Penin, Aleksey A; Bazykin, Georgii A; Etingova, Anna E; Mugue, Nikolai S; Kondrashov, Alexey S; Yampolsky, Lev Y

2017-01-01

Endemic species flocks inhabiting ancient lakes, oceanic islands and other long-lived isolated habitats are often interpreted as adaptive radiations. Yet molecular evidence for directional selection during species flocks radiation is scarce. Using partial transcriptomes of 64 species of Lake Baikal (Siberia, Russia) endemic amphipods and two nonendemic outgroups, we report a revised phylogeny of this species flock and analyse evidence for positive selection within the endemic lineages. We confirm two independent invasions of amphipods into Baikal and demonstrate that several morphological features of Baikal amphipods, such as body armour and reduction in appendages and sensory organs, evolved in several lineages in parallel. Radiation of Baikal amphipods has been characterized by short phylogenetic branches and frequent episodes of positive selection which tended to be more frequent in the early phase of the second invasion of amphipods into Baikal when the most intensive diversification occurred. Notably, signatures of positive selection are frequent in genes encoding mitochondrial membrane proteins with electron transfer chain and ATP synthesis functionality. In particular, subunits of both the membrane and substrate-level ATP synthases show evidence of positive selection in the plankton species Macrohectopus branickii, possibly indicating adaptation to active plankton lifestyle and to survival under conditions of low temperature and high hydrostatic pressures known to affect membranes functioning. Other functional categories represented among genes likely to be under positive selection include Ca-binding muscle-related proteins, possibly indicating adaptation to Ca-deficient low mineralization Baikal waters. © 2016 John Wiley & Sons Ltd.

High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2

Directory of Open Access Journals (Sweden)

Hellberg Michael E

2010-05-01

Full Text Available Abstract Background Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching. Results In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus, a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella possess proteins structurally similar to tachylectin-2. Conclusions Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1 part of Oculina's innate immunity repertoire, and 2 evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change.

Destabilization in the isomeric nitrobenzonitriles: an experimental thermochemical study

International Nuclear Information System (INIS)

Roux, Maria Victoria; Jimenez, Pilar; Davalos, Juan Z.; Temprado, Manuel; Liebman, Joel F.

2003-01-01

The enthalpies of combustion and of sublimation, respectively, of the three isomeric nitrobenzonitriles have been measured: o-, {(-3456.3±2.9), (88.1±1.4)} kJ·mol -1 ; m-, {(-3442.8±3.3), (92.8±0.3)} kJ·mol -1 ; p-, {(-3448.2±3.6), (91.1±1.3)} kJ·mol -1 . In turn, from these values, the standard molar enthalpies of formation for the condensed and gaseous state, respectively, have been derived: o-, {(130.1±3.1), (218.2±3.4)} kJ·mol -1 ; m-, {(116.5±3.5), (209.3±3.5)} kJ·mol -1 ; p-, {(122.0±3.8), (213.1±4.0)} kJ·mol -1 . Destabilization energies associated with the presence of the two electron-withdrawing groups have been determined, for o-, m-, and p-nitrobenzonitrile, {(17.6±4.1), (8.7±4.2), and (12.5±4.6)} kJ·mol -1 , respectively, and are consistent with those obtained for the corresponding sets of isomeric methyl benzenedicarboxylates, dicyanobenzenes, dinitrobenzenes, and (neutral and ionized) nitrobenzoic acids

Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast.

Science.gov (United States)

Belew, Ashton T; Advani, Vivek M; Dinman, Jonathan D

2011-04-01

Although first discovered in viruses, previous studies have identified operational -1 ribosomal frameshifting (-1 RF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. Here, four yeast -1 RF signals are shown to promote significant mRNA destabilization through the nonsense mediated mRNA decay pathway (NMD), and genetic evidence is presented suggesting that they may also operate through the no-go decay pathway (NGD) as well. Yeast EST2 mRNA is highly unstable and contains up to five -1 RF signals. Ablation of the -1 RF signals or of NMD stabilizes this mRNA, and changes in -1 RF efficiency have opposing effects on the steady-state abundance of the EST2 mRNA. These results demonstrate that endogenous -1 RF signals function as mRNA destabilizing elements through at least two molecular pathways in yeast. Consistent with current evolutionary theory, phylogenetic analyses suggest that -1 RF signals are rapidly evolving cis-acting regulatory elements. Identification of high confidence -1 RF signals in ∼10% of genes in all eukaryotic genomes surveyed suggests that -1 RF is a broadly used post-transcriptional regulator of gene expression.

DISCRIMINATIVE MODEL OF CERTAIN MOTOR INDICATORS OF FOOTBALL PLAYERS AS SELECTION CRITERIA FOR TEAM POSITION

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Goran Vučković

2013-07-01

Full Text Available Well-designed and implemented selection is one of the important prerequisites for achieving the expected results in the modern competitive sport at all levels. The aim of this work was to determine how the selection was made for Serbian League players, on the basis of their certain motor parameters and the positions in the team. A sample of 25 senior players of a football team competing in the Serbian League is divided into four sub-samples, based on team positions. For assessment of motor characteristics following tests were used: long jump (LJ, Abalac test (AT; 10 seconds push-ups (PU, 30 seconds trunk bends (TB, 20 meter flying start running (20FSR, 20 meter high start running (20HSR, 50 meter high start running (50HSR and Cooper test (CT . Based on the obtained results it can be concluded that there are significant differences for variable 20FSR and variable CT (F = 3754, 9835, p = .027, .000, respectively. Three canonical discriminant functions were singled out, where the first explained even 84.6%, the second 14.5% and the third only 1% of the total variance, or in summary first two functions explained 99.0% of the variance. It can be concluded that the selected players, in terms of the position in the team, distinguished first by performing on the Cooper test, followed by the result of 20 meter flying start running, 20 meter high start running, 50 meter high start running, trunk bends, and finally by Abalac test, push-ups and long jump. Observed as a function of certain motor characteristics, it could be concluded that in the selection of players in terms of the playing position confidence level was 72.0% in general level, with the most reliable for goalkeepers (100%, midfielders (71.4% and defensive players (70.0%, while the smallest was at strikers (50%.

Positive selection rather than relaxation of functional constraint drives the evolution of vision during chicken domestication.

Science.gov (United States)

Wang, Ming-Shan; Zhang, Rong-Wei; Su, Ling-Yan; Li, Yan; Peng, Min-Sheng; Liu, He-Qun; Zeng, Lin; Irwin, David M; Du, Jiu-Lin; Yao, Yong-Gang; Wu, Dong-Dong; Zhang, Ya-Ping

2016-05-01

As noted by Darwin, chickens have the greatest phenotypic diversity of all birds, but an interesting evolutionary difference between domestic chickens and their wild ancestor, the Red Junglefowl, is their comparatively weaker vision. Existing theories suggest that diminished visual prowess among domestic chickens reflect changes driven by the relaxation of functional constraints on vision, but the evidence identifying the underlying genetic mechanisms responsible for this change has not been definitively characterized. Here, a genome-wide analysis of the domestic chicken and Red Junglefowl genomes showed significant enrichment for positively selected genes involved in the development of vision. There were significant differences between domestic chickens and their wild ancestors regarding the level of mRNA expression for these genes in the retina. Numerous additional genes involved in the development of vision also showed significant differences in mRNA expression between domestic chickens and their wild ancestors, particularly for genes associated with phototransduction and photoreceptor development, such as RHO (rhodopsin), GUCA1A, PDE6B and NR2E3. Finally, we characterized the potential role of the VIT gene in vision, which experienced positive selection and downregulated expression in the retina of the village chicken. Overall, our results suggest that positive selection, rather than relaxation of purifying selection, contributed to the evolution of vision in domestic chickens. The progenitors of domestic chickens harboring weaker vision may have showed a reduced fear response and vigilance, making them easier to be unconsciously selected and/or domesticated.

Engineering FKBP-Based Destabilizing Domains to Build Sophisticated Protein Regulation Systems.

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Wenlin An

Full Text Available Targeting protein stability with small molecules has emerged as an effective tool to control protein abundance in a fast, scalable and reversible manner. The technique involves tagging a protein of interest (POI with a destabilizing domain (DD specifically controlled by a small molecule. The successful construction of such fusion proteins may, however, be limited by functional interference of the DD epitope with electrostatic interactions required for full biological function of proteins. Another drawback of this approach is the remaining endogenous protein. Here, we combined the Cre-LoxP system with an advanced DD and generated a protein regulation system in which the loss of an endogenous protein, in our case the tumor suppressor PTEN, can be coupled directly with a conditionally fine-tunable DD-PTEN. This new system will consolidate and extend the use of DD-technology to control protein function precisely in living cells and animal models.

Positive selection and propeptide repeats promote rapid interspecific divergence of a gastropod sperm protein.

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Hellberg, M E; Moy, G W; Vacquier, V D

2000-03-01

Male-specific proteins have increasingly been reported as targets of positive selection and are of special interest because of the role they may play in the evolution of reproductive isolation. We report the rapid interspecific divergence of cDNA encoding a major acrosomal protein of unknown function (TMAP) of sperm from five species of teguline gastropods. A mitochondrial DNA clock (calibrated by congeneric species divided by the Isthmus of Panama) estimates that these five species diverged 2-10 MYA. Inferred amino acid sequences reveal a propeptide that has diverged rapidly between species. The mature protein has diverged faster still due to high nonsynonymous substitution rates (> 25 nonsynonymous substitutions per site per 10(9) years). cDNA encoding the mature protein (89-100 residues) shows evidence of positive selection (Dn/Ds > 1) for 4 of 10 pairwise species comparisons. cDNA and predicted secondary-structure comparisons suggest that TMAP is neither orthologous nor paralogous to abalone lysin, and thus marks a second, phylogenetically independent, protein subject to strong positive selection in free-spawning marine gastropods. In addition, an internal repeat in one species (Tegula aureotincta) produces a duplicated cleavage site which results in two alternatively processed mature proteins differing by nine amino acid residues. Such alternative processing may provide a mechanism for introducing novel amino acid sequence variation at the amino-termini of proteins. Highly divergent TMAP N-termini from two other tegulines (Tegula regina and Norrisia norrisii) may have originated by such a mechanism.

A synbio approach for selection of highly expressed gene variants in Gram-positive bacteria

DEFF Research Database (Denmark)

Ferro, Roberto; Rennig, Maja; Hernández Rollán, Cristina

2018-01-01

with a long history in food fermentation. We have developed a synbio approach for increasing gene expression in two Gram-positive bacteria. First of all, the gene of interest was coupled to an antibiotic resistance gene to create a growth-based selection system. We then randomised the translation initiation...... region (TIR) preceding the gene of interest and selected clones that produced high protein titres, as judged by their ability to survive on high concentrations of antibiotic. Using this approach, we were able to significantly increase production of two industrially relevant proteins; sialidase in B....... subtilis and tyrosine ammonia lyase in L. lactis. Gram-positive bacteria are widely used to produce industrial enzymes. High titres are necessary to make the production economically feasible. The synbio approach presented here is a simple and inexpensive way to increase protein titres, which can be carried...

Positive selection and ancient duplications in the evolution of class B floral homeotic genes of orchids and grasses

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Koch Marcus A

2009-04-01

Full Text Available Abstract Background Positive selection is recognized as the prevalence of nonsynonymous over synonymous substitutions in a gene. Models of the functional evolution of duplicated genes consider neofunctionalization as key to the retention of paralogues. For instance, duplicate transcription factors are specifically retained in plant and animal genomes and both positive selection and transcriptional divergence appear to have played a role in their diversification. However, the relative impact of these two factors has not been systematically evaluated. Class B MADS-box genes, comprising DEF-like and GLO-like genes, encode developmental transcription factors essential for establishment of perianth and male organ identity in the flowers of angiosperms. Here, we contrast the role of positive selection and the known divergence in expression patterns of genes encoding class B-like MADS-box transcription factors from monocots, with emphasis on the family Orchidaceae and the order Poales. Although in the monocots these two groups are highly diverse and have a strongly canalized floral morphology, there is no information on the role of positive selection in the evolution of their distinctive flower morphologies. Published research shows that in Poales, class B-like genes are expressed in stamens and in lodicules, the perianth organs whose identity might also be specified by class B-like genes, like the identity of the inner tepals of their lily-like relatives. In orchids, however, the number and pattern of expression of class B-like genes have greatly diverged. Results The DEF-like genes from Orchidaceae form four well-supported, ancient clades of orthologues. In contrast, orchid GLO-like genes form a single clade of ancient orthologues and recent paralogues. DEF-like genes from orchid clade 2 (OMADS3-like genes are under less stringent purifying selection than the other orchid DEF-like and GLO-like genes. In comparison with orchids, purifying selection

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

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Dall’Olio Giovanni

2012-06-01

Full Text Available Abstract Background Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Results Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. Conclusions These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show

Crystallization and preliminary electron diffraction study to 3. 7 A of DNA helix-destabilizing protein gp32*I

Energy Technology Data Exchange (ETDEWEB)

Chiu, W; Hosoda, J

1978-01-01

A two-dimensionally large and thin crystal has been obtained from gp32*I, a proteolytically digested product of a DNA helix-destabilizing protein coded by gene 32 in bacteriophage T4. High-resolution electron diffraction patterns (approx. 3.7 A) are recorded from both unstained and stained protein crystals embedded in glucose. The crystal is of orthorhombic space group with a = 62.9 A and b = 47.3 A.

Study of the man-caused destabilization consequences to the Semipalatinsk test site subsurface

International Nuclear Information System (INIS)

Gorbunova, Eh.M.

2004-01-01

Conduction of underground nuclear explosions (UNE) at the territory of the Semipalatinsk Test Site (STS) has led to irreversible deformation of the geological environment. The carried out experimental researches on study of the UNE effect on the rocks massif allowed to ascertain the basic mechanisms of man-caused subsurface destabilization, which is a change in the physic-mechanical characteristics and filtering structure of the background medium, hydrogeodynamic and radiation situation. The consequences of the post-explosion deformations detected in the massif conjugate not only with the epicenter zone of UNE, but are also related to the structural boundaries of various range (to faults, lithologic contacts, boundaries of inhomogeneous media). The consequences were partially detected on the ground surface as well. (author)

Evidence of Positive Selection of Aquaporins Genes from Pontoporia blainvillei during the Evolutionary Process of Cetaceans.

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Simone Lima São Pedro

Full Text Available Marine mammals are well adapted to their hyperosmotic environment. Several morphological and physiological adaptations for water conservation and salt excretion are known to be present in cetaceans, being responsible for regulating salt balance. However, most previous studies have focused on the unique renal physiology of marine mammals, but the molecular bases of these mechanisms remain poorly explored. Many genes have been identified to be involved in osmotic regulation, including the aquaporins. Considering that aquaporin genes were potentially subject to strong selective pressure, the aim of this study was to analyze the molecular evolution of seven aquaporin genes (AQP1, AQP2, AQP3, AQP4, AQP6, AQP7, and AQP9 comparing the lineages of cetaceans and terrestrial mammals.Our results demonstrated strong positive selection in cetacean-specific lineages acting only in the gene for AQP2 (amino acids 23, 83, 107,179, 180, 181, 182, whereas no selection was observed in terrestrial mammalian lineages. We also analyzed the changes in the 3D structure of the aquaporin 2 protein. Signs of strong positive selection in AQP2 sites 179, 180, 181, and 182 were unexpectedly identified only in the baiji lineage, which was the only river dolphin examined in this study. Positive selection in aquaporins AQP1 (45, AQP4 (74, AQP7 (342, 343, 356 was detected in cetaceans and artiodactyls, suggesting that these events are not related to maintaining water and electrolyte homeostasis in seawater.Our results suggest that the AQP2 gene might reflect different selective pressures in maintaining water balance in cetaceans, contributing to the passage from the terrestrial environment to the aquatic. Further studies are necessary, especially those including other freshwater dolphins, who exhibit osmoregulatory mechanisms different from those of marine cetaceans for the same essential task of maintaining serum electrolyte balance.

On the structure of the two-stream instability–complex G-Hamiltonian structure and Krein collisions between positive- and negative-action modes

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ruili; Liu, Jian; Xiao, Jianyuan [Department of Modern Physics and School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, Anhui 230026 (China); Key Laboratory of Geospace Environment, CAS, Hefei, Anhui 230026 (China); Qin, Hong, E-mail: hongqin@princeton.edu [Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (United States); Department of Modern Physics and School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, Anhui 230026 (China); Davidson, Ronald C. [Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (United States)

2016-07-15

The two-stream instability is probably the most important elementary example of collective instabilities in plasma physics and beam-plasma systems. For a warm plasma with two charged particle species, the instability diagram of the two-stream instability based on a 1D warm-fluid model exhibits an interesting band structure that has not been explained. We show that the band structure for this instability is the consequence of the Hamiltonian nature of the warm two-fluid system. Interestingly, the Hamiltonian nature manifests as a complex G-Hamiltonian structure in wave-number space, which directly determines the instability diagram. Specifically, it is shown that the boundaries between the stable and unstable regions are locations for Krein collisions between eigenmodes with different Krein signatures. In terms of physics, this rigorously implies that the system is destabilized when a positive-action mode resonates with a negative-action mode, and that this is the only mechanism by which the system can be destabilized. It is anticipated that this physical mechanism of destabilization is valid for other collective instabilities in conservative systems in plasma physics, accelerator physics, and fluid dynamics systems, which admit infinite-dimensional Hamiltonian structures.

Response of knee fibrocartilage to joint destabilization.

Science.gov (United States)

Dyment, N A; Hagiwara, Y; Jiang, X; Huang, J; Adams, D J; Rowe, D W

2015-06-01

A major challenge to understanding osteoarthritis (OA) pathology is identifying the cellular events that precede the onset of cartilage damage. The objective of this study is to determine the effect of joint destabilization on early changes to fibrocartilage in the joint. The anterior cruciate ligament was transected in collagen reporter mice (Col1CFP and ColXRFP). Mineralization labels were given every 2 weeks to measure new mineralized cartilage apposition. Novel fluorescent histology of mineralized tissue was used to characterize the changes in fibrocartilage at 2 and 4 weeks post-injury. Changes in fibrocartilaginous structures of the joint occur as early as 2 weeks after injury and are well developed by 4 weeks. The alterations are seen in multiple entheses and in the medial surface of the femoral and tibial condyles. In the responding entheses, mineral apposition towards the ligament midsubstance results in thickening of the mineralize fibrocartilage. These changes are associated with increases in ColX-RFP, Col1-CFP reporter activity and alkaline phosphatase enzyme activity. Mineral apposition also occurs in the fibrocartilage of the non-articular regions of the medial condyles by 2 weeks and develops into osteophytes by 4 weeks post-injury. An unexpected observation is punctate expression of tartrate resistant acid phosphatase activity in unmineralized fibrochondrocytes adjacent to active appositional mineralization. These observations suggest that fibrocartilage activates prior to degradation of the articular cartilage. Thus clinical and histological imaging of fibrocartilage may be an earlier indicator of disease initiation and may indicate a more appropriate time to start preventative treatment. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Optimization of DIII-D discharges to avoid AE destabilization

Science.gov (United States)

Varela, Jacobo; Spong, Donald; Garcia, Luis; Huang, Juan; Murakami, Masanori

2017-10-01

The aim of the study is to analyze the stability of Alfven Eigenmodes (AE) perturbed by energetic particles (EP) during DIII-D operation. We identify the optimal NBI operational regimes that avoid or minimize the negative effects of AE on the device performance. We use the reduced MHD equations to describe the linear evolution of the poloidal flux and the toroidal component of the vorticity in a full 3D system, coupled with equations of density and parallel velocity moments for the energetic particles, including the effect of the acoustic modes. We add the Landau damping and resonant destabilization effects using a closure relation. We perform parametric studies of the MHD and AE stability, taking into account the experimental profiles of the thermal plasma and EP, also using a range of values of the energetic particles β, density and velocity as well the effect of the toroidal couplings. We reproduce the AE activity observed in high poloidal β discharge at the pedestal and reverse shear discharges. This material based on work is supported both by the U.S. Department of Energy, Office of Science, under Contract DE-AC05-00OR22725 with UT-Battelle, LLC. Research sponsored in part by the Ministerio de Economia y Competitividad of Spain under the project.

The destabilizing influence of heat flow on the geological environment during underground nuclear explosions

International Nuclear Information System (INIS)

Politikov, M.I.; Kamberov, I.M.; Krivchenko, V.F.; Lukashenko, S.N.; Solodukhin, V.P.

2001-01-01

The study has determined the fact that the processes of gas-radioactive ectoplasm intrusion from nuclear cavities in the geological environment bring the significant contribution in bosom destabilizing besides the mechanical rock destruction as affected by underground nuclear explosions. Not only heat field forming that reduces the rock resistance and increases its porosity is related to it, but also the forming, on the way, of man-caused contamination aureoles of the geological environment, including the underground water bearing horizon. Unfortunately, this problem is hardly studied, mainly for the lack of reliable apparatus and methods. Judging by the results of information search, the best way to solve the problem is not yet known. (author)

Design and optimization of selective azaindole amide M1 positive allosteric modulators.

Science.gov (United States)

Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

2016-01-15

Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Influence of Oblique Angle Forced Exercise in Surgically Destabilized Stifle Joints Is Synergistic with Bone, but Antagonistic with Cartilage in an Ovine Model of Osteoarthritis

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Rachel J. Hill

2017-01-01

Full Text Available Large animal models of osteoarthritis are a necessary testing ground for FDA approval of human medicine applications. Sheep models have advantages over other available large animals, but development and progression of osteoarthritis in sheep is exceedingly slow, which handicaps progress in development of potential treatments. We combined oblique angle forced exercise to increase stress on the stifle, with surgical destabilization to hasten the development of osteoarthritis in ewes. Methods for early detection of clinical signs included radiography, urine, and serum biomarker assays and gait analysis and ex vivo we used microcomputed tomography and macroscopic joint analysis. Our model was able to produce clinically detectable signs of osteoarthritis in a relatively short period (14 weeks. Changes in bone were highly correlated between microcomputed tomography and radiographic analysis and changes in cartilage correlated well between urinary glycosaminoglycan levels and serum aggrecanase analyses. Exercise improved the negative effects of destabilization in bone but exacerbated the negative effects of destabilization in cartilage. These observations suggest that we may need to consider treatments for bone and cartilage separately. These results represent an improved large animal model of osteoarthritis with rapid onset of disease and superior detection of bone and soft tissue changes.

PROTEOLYTIC REMOVAL OF THE CARBOXYL TERMINUS OF THE T4 GENE 32 HELIX-DESTABILIZING PROTEIN ALTERS THE T4 IN VITRO REPLICATION COMPLEX

Energy Technology Data Exchange (ETDEWEB)

Burke, R.L.; Alberts, B.M.; Hosoda, J.

1980-07-01

The proteolytic removal of about 60 amino acids from the COOH terminus of the bacteriophage T4 helix-destabilizing protein (gene 32 protein) produces 32*I, a 27,000-dalton fragment which still binds tightly and cooperatively to single-stranded DNA. The substitution of 32*I protein for intact 32 protein in the seven-protein T4 replication complex results in dramatic changes in some of the reactions catalyzed by this in vitro DNA replication system, while leaving others largely unperturbed. (1) Like intact 32 protein, the 32*I protein promotes DNA synthesis by the DNA polymerase when the T4 polymerase accessory proteins (gene 44/62 and 45 proteins) are also present. The host helix-destabilizing protein (Escherichia coli ssb protein) cannot replace the 32*I protein for this synthesis. (2) Unlike intact 32 protein, 32*I protein strongly inhibits DNA synthesis catalyzed by the T4 DNA polymerase alone on a primed single-stranded DNA template. (3) Unlike intact 32 protein, the 32*I protein strongly inhibits RNA primer synthesis catalyzed by the T4 gene 41 and 61 proteins and also reduces the efficiency of RNA primer utilization. As a result, de novo DNA chain starts are blocked completely in the complete T4 replication system, and no lagging strand DNA synthesis occurs. (4) The 32*I protein does not bind to either the T4 DNA polymerase or to the T4 gene 61 protein in the absence of DNA; these associations (detected with intact 32 protein) would therefore appear to be essential for the normal control of 32 protein activity, and to account at least in part for observations 2 and 3, above. We propose that the COOH-terminal domain of intact 32 protein functions to guide its interactions with the T4 DNA polymerase and the T4 gene 61 RNA-priming protein. When this domain is removed, as in 32*I protein, the helix destabilization induced by the protein is controlled inadequately, so that polymerizing enzymes tend to be displaced from the growing 3{prime}-OH end of a

Destabilization of Human Insulin Fibrils by Peptides of Fruit Bromelain Derived From Ananas comosus (Pineapple).

Science.gov (United States)

Das, Sromona; Bhattacharyya, Debasish

2017-12-01

Deposition of insulin aggregates in human body leads to dysfunctioning of several organs. Effectiveness of fruit bromelain from pineapple in prevention of insulin aggregate was investigated. Proteolyses of bromelain was done as par human digestive system and the pool of small peptides was separated from larger peptides and proteins. Under conditions of growth of insulin aggregates from its monomers, this pool of peptides restricted the reaction upto formation of oligomers of limited size. These peptides also destabilized preformed insulin aggregates to oligomers. These processes were followed fluorimetrically using Thioflavin T and 1-ANS, size-exclusion HPLC, dynamic light scattering, atomic force microscopy, and transmission electron microscopy. Sequences of insulin (A and B chains) and bromelain were aligned using Clustal W software to predict most probable sites of interactions. Synthetic tripeptides corresponding to the hydrophobic interactive sites of bromelain showed disaggregation of insulin suggesting specificity of interactions. The peptides GG and AAA serving as negative controls showed no potency in destabilization of aggregates. Disaggregation potency of the peptides was also observed when insulin was deposited on HepG2 liver cells where no formation of toxic oligomers occurred. Amyloidogenic des-octapeptide (B23-B30 of insulin) incapable of cell signaling showed cytotoxicity similar to insulin. This toxicity could be neutralized by bromelain derived peptides. FT-IR and far-UV circular dichroism analysis indicated that disaggregated insulin had structure distinctly different from that of its hexameric (native) or monomeric states. Based on the stoichiometry of interaction and irreversibility of disaggregation, the mechanism/s of the peptides and insulin interactions has been proposed. J. Cell. Biochem. 118: 4881-4896, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

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Tali Gidalevitz

2009-03-01

Full Text Available Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles.

Ground Receiving Station Reference Pair Selection Technique for a Minimum Configuration 3D Emitter Position Estimation Multilateration System

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Abdulmalik Shehu Yaro

2017-01-01

Full Text Available Multilateration estimates aircraft position using the Time Difference Of Arrival (TDOA with a lateration algorithm. The Position Estimation (PE accuracy of the lateration algorithm depends on several factors which are the TDOA estimation error, the lateration algorithm approach, the number of deployed GRSs and the selection of the GRS reference used for the PE process. Using the minimum number of GRSs for 3D emitter PE, a technique based on the condition number calculation is proposed to select the suitable GRS reference pair for improving the accuracy of the PE using the lateration algorithm. Validation of the proposed technique was performed with the GRSs in the square and triangular GRS configuration. For the selected emitter positions, the result shows that the proposed technique can be used to select the suitable GRS reference pair for the PE process. A unity condition number is achieved for GRS pair most suitable for the PE process. Monte Carlo simulation result, in comparison with the fixed GRS reference pair lateration algorithm, shows a reduction in PE error of at least 70% for both GRS in the square and triangular configuration.

Influence of needle position on lumbar segmental nerve root block selectivity.

Science.gov (United States)

Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

2006-01-01

In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

Alpha particle destabilization of the TAE modes

International Nuclear Information System (INIS)

Cheng, C.Z.

1991-01-01

The high frequency, low mode number toroidicity-induced Alfven eigenmodes (TAE) are shown to be driven unstable by the circulating and/or trapped α-particles through the wave-particle resonances. For a poloidal harmonic to satisfy the resonance condition it requires that the α-particle birth speed v α ≥ v A /(2|m-nq|), where v A is the Alfven speed, m is the poloidal mode number, and n is the toroidal mode number. To destabilize the TAE modes, the inverse Landau damping associated with the α-particle pressure gradient free energy must overcome the velocity space Landau damping due to both the slowing-down α-particle and the core Maxwellian electron and ion distributions. Stability criteria in terms of the α-particle beta β α , α-particle pressure gradient parameter (ω * /ω A ) (ω * is the α-particle diamagnetic drift frequency), and (v α /v A ) parameters are presented for TFTR, CIT, and ITER tokamaks. The volume averaged α-particle beta threshold for TAE instability also depends sensitively on the core electron and ion temperature. Typically the volume averaged α-particle beta threshold is in the order of 10 -4 if the continuum damping effect is absent. Typical growth rates of the n = 1 TAE mode can be in the order of 10 -2 ω A , where ω A = v A /qR. Stability of higher n TAE modes is also studied. Other types of global Alfven waves are stable due to sideband mode continuum damping resulting from toroidal coupling effects. If the Alfven continuum gap does not exist across the whole minor radius, continuum damping exists for some poloidal harmonics. The continuum damping effect is studied by employing both a resistive MHD stability code (NOVA-R) and an analytical matching method, and the results are presented. 1 ref

Thinking about a Limited Future Enhances the Positivity of Younger and Older Adults’ Recall: Support for Socioemotional Selectivity Theory

OpenAIRE

Barber, Sarah J.; Opitz, Philipp C.; Martins, Bruna; Sakaki, Michiko; Mather, Mara

2016-01-01

Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the “positivity effect,” and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus...

Assessment of destabilizing factor for automatic control systems in propulsion systems of mechatronic and maritime transport objects

Science.gov (United States)

Zhilenkov, A. A.; Kapitonov, A. A.

2017-10-01

It is known that many of today’s ships and vessels have a shaft generator as a part of their power plants. Modern automatic control systems used in the world’s fleet do not enable their shaft generators to operate in parallel with the main diesel generators for long-term sustenance of the total load of the ship network. On the other hand, according to our calculations and experiments, a shaft generator operated in parallel with the main power plant helps save at least 10% of fuel while making the power system of the ship more efficient, reliable, and eco-friendly. The fouling and corrosion of the propeller as well as the weather conditions of navigation affect its modulus of resistance. It changes the free component of the transient process of shaft generator stress frequency changes in transient processes. While the shaft generator and the diesel generator of the ship power plant are paralleled, there emerges an angle between their EMF. This results in equalizing currents generated between them. The altering torque in the drive-shaft line—propeller system causes torsional fluctuations of the ship shaft line. To compensate for the effect of destabilizing factors and torsional fluctuations of the shaft line on the dynamic characteristics of the transient process that alters the RPM of the main engine, sliding mode controls can be used. To synthesize such a control, one has to evaluate the effect of destabilizing factors.

Genomic analysis suggests that mRNA destabilization by the microprocessor is specialized for the auto-regulation of Dgcr8.

Directory of Open Access Journals (Sweden)

Archana Shenoy

2009-09-01

Full Text Available The Microprocessor, containing the RNA binding protein Dgcr8 and RNase III enzyme Drosha, is responsible for processing primary microRNAs to precursor microRNAs. The Microprocessor regulates its own levels by cleaving hairpins in the 5'UTR and coding region of the Dgcr8 mRNA, thereby destabilizing the mature transcript.To determine whether the Microprocessor has a broader role in directly regulating other coding mRNA levels, we integrated results from expression profiling and ultra high-throughput deep sequencing of small RNAs. Expression analysis of mRNAs in wild-type, Dgcr8 knockout, and Dicer knockout mouse embryonic stem (ES cells uncovered mRNAs that were specifically upregulated in the Dgcr8 null background. A number of these transcripts had evolutionarily conserved predicted hairpin targets for the Microprocessor. However, analysis of deep sequencing data of 18 to 200nt small RNAs in mouse ES, HeLa, and HepG2 indicates that exonic sequence reads that map in a pattern consistent with Microprocessor activity are unique to Dgcr8.We conclude that the Microprocessor's role in directly destabilizing coding mRNAs is likely specifically targeted to Dgcr8 itself, suggesting a specialized cellular mechanism for gene auto-regulation.

Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3

Science.gov (United States)

Zhao, Li-Hua; Zhou, X Edward; Yi, Wei; Wu, Zhongshan; Liu, Yue; Kang, Yanyong; Hou, Li; de Waal, Parker W; Li, Suling; Jiang, Yi; Scaffidi, Adrian; Flematti, Gavin R; Smith, Steven M; Lam, Vinh Q; Griffin, Patrick R; Wang, Yonghong; Li, Jiayang; Melcher, Karsten; Xu, H Eric

2015-01-01

Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the α/β-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCFD3 that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process. PMID:26470846

A cellular model of memory reconsolidation involves reactivation-induced destabilization and restabilization at the sensorimotor synapse in Aplysia.

Science.gov (United States)

Lee, Sue-Hyun; Kwak, Chuljung; Shim, Jaehoon; Kim, Jung-Eun; Choi, Sun-Lim; Kim, Hyoung F; Jang, Deok-Jin; Lee, Jin-A; Lee, Kyungmin; Lee, Chi-Hoon; Lee, Young-Don; Miniaci, Maria Concetta; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

2012-08-28

The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia, and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron synapse that mediates long-term sensitization is also destabilized by protein degradation and is restabilized by protein synthesis after synaptic reactivation, a procedure that parallels memory retrieval or retraining evident on the behavioral level. These results provide direct evidence that the same synapses that store the long-term memory trace encoded by changes in the strength of synaptic connections critical for sensitization are disrupted and reconstructed after signal retrieval.

Positive selection in the SLC11A1 gene in the family Equidae.

Science.gov (United States)

Bayerova, Zuzana; Janova, Eva; Matiasovic, Jan; Orlando, Ludovic; Horin, Petr

2016-05-01

Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence identity across the family. Single nucleotide polymorphisms (SNPs) were found in the coding and noncoding regions of the gene. Seven codon sites were identified to be under strong purifying selection. Codons located in three regions, including the glycosylated extracellular loop, were shown to be under diversifying selection. A 3-bp indel resulting in a deletion of the amino acid 321 in the predicted protein was observed in all horses, while it has been maintained in all other equid species. This codon comprised in an N-glycosylation site was found to be under positive selection. Interspecific variation in the presence of predicted N-glycosylation sites was observed.

Antiproliferative efficacy of curcumin mimics through microtubule destabilization.

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Khwaja, Sadiya; Fatima, Kaneez; Hasanain, Mohammad; Behera, Chittaranjan; Kour, Avneet; Singh, Arjun; Luqman, Suaib; Sarkar, Jayanta; Chanda, Debabrata; Shanker, Karuna; Gupta, A K; Mondhe, D M; Negi, Arvind S

2018-05-10

Curcumin possesses an attractive chemical structure with highly conjugated diferuloylmethane core. Curcumin mimics have been designed and prepared with an additional bridged phenyl ring in conjugation. Fourteen diverse analogues were evaluated against a panel of human cancer cell lines. The best analogue of the series i.e. compound 6a exhibited potent cytotoxicity against A431, epidermoid carcinoma cell line (IC 50  = 1.5 μM) and DLD1, colorectal adenocarcinoma cell line (IC 50  = 6.9 μM). In tubulin kinetics experiment, compound 6a destabilized polymerisation process (IC 50  = 4.68 μM). In cell cycle analysis, compound 6a exerted G2/M phase arrest in A431 cells and induced apoptosis. In Ehrlich Ascites Carcinoma in Swiss-albino mice, compound 6a showed 78.6% tumour reduction at 80 mg/kg dose and 57% solid tumour reduction at 150 mg/kg dose. Further, in acute-oral toxicity experiment in rodent model, compound 6a was given in three different oral doses to Swiss albino mice. There were non-significant changes in various biochemical parameters and major body organs studied, including their absolute and relative weights. It was tolerable up to 300 mg/kg dose in Swiss-albino mice. The present study shows that the novel curcumin mimic 6a is a safe and efficacious anticancer compound. However, it needs to be optimized for better efficacy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effect of antiviral treatment and host susceptibility on positive selection in hepatitis C virus (HCV).

Science.gov (United States)

Jiménez-Hernández, Nuria; Sentandreu, Vicente; Castro, José A; Torres-Puente, Manuela; Bracho, Alma; García-Robles, Inmaculada; Ortega, Enrique; Del Olmo, Juan; Carnicer, Fernando; González-Candelas, Fernando; Moya, Andrés

2008-02-01

We have conducted a large sequence study of the E1-E2 and NS5A regions of the HCV, subtypes 1a and b, both in patients previously treated with interferon, and untreated patients, who later responded, or not, to a combination therapy based on interferon plus ribavirin. We have examined the role played by the number of positively selected sites on disease progression and its relationship with several variables such as patients' age, sex and their risk of acquiring the disease. We have detected three groups of patients that respond or not to combination therapy: responders of intermediate age, older non-responders and young non-responders, they possess an increasing average number of positively selected sites in the E1-E2 region, respectively. We conclude that the host's genetic factors play an important role in whether the disease is contained or becomes chronic.

A synbio approach for selection of highly expressed gene variants in Gram-positive bacteria.

Science.gov (United States)

Ferro, Roberto; Rennig, Maja; Hernández-Rollán, Cristina; Daley, Daniel O; Nørholm, Morten H H

2018-03-08

The market for recombinant proteins is on the rise, and Gram-positive strains are widely exploited for this purpose. Bacillus subtilis is a profitable host for protein production thanks to its ability to secrete large amounts of proteins, and Lactococcus lactis is an attractive production organism with a long history in food fermentation. We have developed a synbio approach for increasing gene expression in two Gram-positive bacteria. First of all, the gene of interest was coupled to an antibiotic resistance gene to create a growth-based selection system. We then randomised the translation initiation region (TIR) preceding the gene of interest and selected clones that produced high protein titres, as judged by their ability to survive on high concentrations of antibiotic. Using this approach, we were able to significantly increase production of two industrially relevant proteins; sialidase in B. subtilis and tyrosine ammonia lyase in L. lactis. Gram-positive bacteria are widely used to produce industrial enzymes. High titres are necessary to make the production economically feasible. The synbio approach presented here is a simple and inexpensive way to increase protein titres, which can be carried out in any laboratory within a few days. It could also be implemented as a tool for applications beyond TIR libraries, such as screening of synthetic, homologous or domain-shuffled genes.

Phosphorylation of ARD1 by IKKβ contributes to its destabilization and degradation

International Nuclear Information System (INIS)

Kuo, Hsu-Ping; Lee, Dung-Fang; Xia, Weiya; Lai, Chien-Chen; Li, Long-Yuan; Hung, Mien-Chie

2009-01-01

IκB kinase β (IKKβ), a major kinase downstream of various proinflammatory signals, mediates multiple cellular functions through phosphorylation and regulation of its substrates. On the basis of protein sequence analysis, we identified arrest-defective protein 1 (ARD1), a protein involved in apoptosis and cell proliferation processes in many human cancer cells, as a new IKKβ substrate. We provided evidence showing that ARD1 is indeed a bona fide substrate of IKKβ. IKKβ physically associated with ARD1 and phosphorylated it at Ser209. Phosphorylation by IKKβ destabilized ARD1 and induced its proteasome-mediated degradation. Impaired growth suppression was observed in ARD1 phosphorylation-mimic mutant (S209E)-transfected cells as compared with ARD1 non-phosphorylatable mutant (S209A)-transfected cells. Our findings of molecular interactions between ARD1 and IKKβ may enable further understanding of the upstream regulation mechanisms of ARD1 and of the diverse functions of IKKβ.

SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization

Science.gov (United States)

Finley, Lydia W.S.; Carracedo, Arkaitz; Lee, Jaewon; Souza, Amanda; Egia, Ainara; Zhang, Jiangwen; Teruya-Feldstein, Julie; Moreira, Paula I.; Cardoso, Sandra M.; Clish, Clary B.; Pandolfi, Pier Paolo; Haigis, Marcia C.

2011-01-01

Summary Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates required for biomass generation. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. Mechanistically, SIRT3 mediates metabolic reprogramming by destabilizing hypoxia-inducible factor-1α (HIF1α), a transcription factor that controls glycolytic gene expression. SIRT3 loss increases reactive oxygen species production, leading to HIF1α stabilization. SIRT3 expression is reduced in human breast cancers, and its loss correlates with the upregulation of HIF1α target genes. Finally, we find that SIRT3 overexpression represses glycolysis and proliferation in breast cancer cells, providing a metabolic mechanism for tumor suppression. PMID:21397863

The mass media destabilizes the cultural homogenous regime in Axelrod's model

Energy Technology Data Exchange (ETDEWEB)

Peres, Lucas R; Fontanari, Jose F [Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, Caixa Postal 369, 13560-970 Sao Carlos SP (Brazil)

2010-02-05

An important feature of Axelrod's model for culture dissemination or social influence is the emergence of many multicultural absorbing states, despite the fact that the local rules that specify the agents interactions are explicitly designed to decrease the cultural differences between agents. Here we re-examine the problem of introducing an external, global interaction-the mass media-in the rules of Axelrod's model: in addition to their nearest neighbors, each agent has a certain probability p to interact with a virtual neighbor whose cultural features are fixed from the outset. Most surprisingly, this apparently homogenizing effect actually increases the cultural diversity of the population. We show that, contrary to previous claims in the literature, even a vanishingly small value of p is sufficient to destabilize the homogeneous regime for very large lattice sizes.

Polyalkoxybenzenes from plants. 5. Parsley seed extract in synthesis of azapodophyllotoxins featuring strong tubulin destabilizing activity in the sea urchin embryo and cell culture assays.

Science.gov (United States)

Semenova, Marina N; Kiselyov, Alex S; Tsyganov, Dmitry V; Konyushkin, Leonid D; Firgang, Sergei I; Semenov, Roman V; Malyshev, Oleg R; Raihstat, Mikhail M; Fuchs, Fabian; Stielow, Anne; Lantow, Margareta; Philchenkov, Alex A; Zavelevich, Michael P; Zefirov, Nikolay S; Kuznetsov, Sergei A; Semenov, Victor V

2011-10-27

A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E. These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule as the most active compound. Finally, in Jurkat cells, compound induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway.

A genome-wide signature of positive selection in ancient and recent invasive expansions of the honey bee Apis mellifera.

Science.gov (United States)

Zayed, Amro; Whitfield, Charles W

2008-03-04

Apis mellifera originated in Africa and extended its range into Eurasia in two or more ancient expansions. In 1956, honey bees of African origin were introduced into South America, their descendents admixing with previously introduced European bees, giving rise to the highly invasive and economically devastating "Africanized" honey bee. Here we ask whether the honey bee's out-of-Africa expansions, both ancient and recent (invasive), were associated with a genome-wide signature of positive selection, detected by contrasting genetic differentiation estimates (F(ST)) between coding and noncoding SNPs. In native populations, SNPs in protein-coding regions had significantly higher F(ST) estimates than those in noncoding regions, indicating adaptive evolution in the genome driven by positive selection. This signal of selection was associated with the expansion of honey bees from Africa into Western and Northern Europe, perhaps reflecting adaptation to temperate environments. We estimate that positive selection acted on a minimum of 852-1,371 genes or approximately 10% of the bee's coding genome. We also detected positive selection associated with the invasion of African-derived honey bees in the New World. We found that introgression of European-derived alleles into Africanized bees was significantly greater for coding than noncoding regions. Our findings demonstrate that Africanized bees exploited the genetic diversity present from preexisting introductions in an adaptive way. Finally, we found a significant negative correlation between F(ST) estimates and the local GC content surrounding coding SNPs, suggesting that AT-rich genes play an important role in adaptive evolution in the honey bee.

Enzyme-like specificity in zeolites: a unique site position in mordenite for selective carbonylation of methanol and dimethyl ether with CO.

Science.gov (United States)

Boronat, Mercedes; Martínez-Sánchez, Cristina; Law, David; Corma, Avelino

2008-12-03

The mechanism of methanol carbonylation at different positions of zeolite MOR is investigated by quantum-chemical methods in order to discover which are the active sites that can selectively catalyze the desired reaction. It is shown that when methanol carbonylation competes with hydrocarbon formation, the first reaction occurs preferentially within 8MR channels. However, the unique selectivity for the carbonylation of methanol and dimethyl ether in mordenite is not only due to the size of the 8MR channel: neither process occurs equally at the two T3-O31 and T3-O33 positions. We show that only the T3-O33 positions are selective and that this selectivity is due to the unusual orientation of the methoxy group in relation to the 8MR channel (parallel to the cylinder axis). Only in this situation does the transition state for the attack of CO fit perfectly in the 8MR channel, while the reaction with methanol or DME is sterically impeded. This result explains why T3-O31, while also located in the 8MR channel of mordenite, is not as selective as the T3-O33 position and why ferrierite, although it contains 8MR channels, is less selective than mordenite. The competing effect of water is explained at the molecular level, and the molecular microkinetic reaction model has been established.

Transcriptome profile and unique genetic evolution of positively selected genes in yak lungs.

Science.gov (United States)

Lan, DaoLiang; Xiong, XianRong; Ji, WenHui; Li, Jian; Mipam, Tserang-Donko; Ai, Yi; Chai, ZhiXin

2018-04-01

The yak (Bos grunniens), which is a unique bovine breed that is distributed mainly in the Qinghai-Tibetan Plateau, is considered a good model for studying plateau adaptability in mammals. The lungs are important functional organs that enable animals to adapt to their external environment. However, the genetic mechanism underlying the adaptability of yak lungs to harsh plateau environments remains unknown. To explore the unique evolutionary process and genetic mechanism of yak adaptation to plateau environments, we performed transcriptome sequencing of yak and cattle (Bos taurus) lungs using RNA-Seq technology and a subsequent comparison analysis to identify the positively selected genes in the yak. After deep sequencing, a normal transcriptome profile of yak lung that containing a total of 16,815 expressed genes was obtained, and the characteristics of yak lungs transcriptome was described by functional analysis. Furthermore, Ka/Ks comparison statistics result showed that 39 strong positively selected genes are identified from yak lungs. Further GO and KEGG analysis was conducted for the functional annotation of these genes. The results of this study provide valuable data for further explorations of the unique evolutionary process of high-altitude hypoxia adaptation in yaks in the Tibetan Plateau and the genetic mechanism at the molecular level.

Positive selection in octopus haemocyanin indicates functional links to temperature adaptation.

Science.gov (United States)

Oellermann, Michael; Strugnell, Jan M; Lieb, Bernhard; Mark, Felix C

2015-07-05

Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the

Device for the selective positioning of a component on a tube plate

International Nuclear Information System (INIS)

1974-01-01

The invention relates to a device for the selective positioning of a component on a tube plate. It particularly applies to the positioning of a guide tube head successively opposite all the tubes of the tube bundle of a nuclear reactor steam generator. The large number of tubes in the tube bundle of the steam generator in a pressure water nuclear power station must be checked periodically for any likely corrosion. This check is effected with a Foucault current probe which is inserted in each tube in turn and is connected to a probe signal processing unit. The probe is placed in a flexible guide tube brought in turn in front of each tube of the bundle to be checked. The invention concerns a device to move the opening of a tube guide for a Foucault current detector over the entire surface of the tube plate, thereby providing access to all the tubes whilst limiting the interventions to a single positioning and a single withdrawal of the apparatus for testing all the bundle. Between the two interventions at the beginning and end of the operation, all displacements are remote controlled from outside the dangerous radioacive area [fr

Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

Directory of Open Access Journals (Sweden)

Blandine Patillon

Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

Does positive selection drive transcription factor binding site turnover? A test with Drosophila cis-regulatory modules.

Directory of Open Access Journals (Sweden)

Bin Z He

2011-04-01

Full Text Available Transcription factor binding site(s (TFBS gain and loss (i.e., turnover is a well-documented feature of cis-regulatory module (CRM evolution, yet little attention has been paid to the evolutionary force(s driving this turnover process. The predominant view, motivated by its widespread occurrence, emphasizes the importance of compensatory mutation and genetic drift. Positive selection, in contrast, although it has been invoked in specific instances of adaptive gene expression evolution, has not been considered as a general alternative to neutral compensatory evolution. In this study we evaluate the two hypotheses by analyzing patterns of single nucleotide polymorphism in the TFBS of well-characterized CRM in two closely related Drosophila species, Drosophila melanogaster and Drosophila simulans. An important feature of the analysis is classification of TFBS mutations according to the direction of their predicted effect on binding affinity, which allows gains and losses to be evaluated independently along the two phylogenetic lineages. The observed patterns of polymorphism and divergence are not compatible with neutral evolution for either class of mutations. Instead, multiple lines of evidence are consistent with contributions of positive selection to TFBS gain and loss as well as purifying selection in its maintenance. In discussion, we propose a model to reconcile the finding of selection driving TFBS turnover with constrained CRM function over long evolutionary time.

Evidence for positive selection and recombination hotspots in Deformed wing virus (DWV).

Science.gov (United States)

Dalmon, A; Desbiez, C; Coulon, M; Thomasson, M; Le Conte, Y; Alaux, C; Vallon, J; Moury, B

2017-01-25

Deformed wing virus (DWV) is considered one of the most damaging pests in honey bees since the spread of its vector, Varroa destructor. In this study, we sequenced the whole genomes of two virus isolates and studied the evolutionary forces that act on DWV genomes. The isolate from a Varroa-tolerant bee colony was characterized by three recombination breakpoints between DWV and the closely related Varroa destructor virus-1 (VDV-1), whereas the variant from the colony using conventional Varroa management was similar to the originally described DWV. From the complete sequence dataset, nine independent DWV-VDV-1 recombination breakpoints were detected, and recombination hotspots were found in the 5' untranslated region (5' UTR) and the conserved region encoding the helicase. Partial sequencing of the 5' UTR and helicase-encoding region in 41 virus isolates suggested that most of the French isolates were recombinants. By applying different methods based on the ratio between non-synonymous (dN) and synonymous (dS) substitution rates, we identified four positions that showed evidence of positive selection. Three of these positions were in the putative leader protein (Lp), and one was in the polymerase. These findings raise the question of the putative role of the Lp in viral evolution.

Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins

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Metzger Kelsey J

2010-05-01

Full Text Available Abstract Background CC chemokine receptor proteins (CCR1 through CCR10 are seven-transmembrane G-protein coupled receptors whose signaling pathways are known for their important roles coordinating immune system responses through targeted trafficking of white blood cells. In addition, some of these receptors have been identified as fusion proteins for viral pathogens: for example, HIV-1 strains utilize CCR5, CCR2 and CCR3 proteins to obtain cellular entry in humans. The extracellular domains of these receptor proteins are involved in ligand-binding specificity as well as pathogen recognition interactions. In mammals, the majority of chemokine receptor genes are clustered together; in humans, seven of the ten genes are clustered in the 3p21-24 chromosome region. Gene conversion events, or exchange of DNA sequence between genes, have been reported in chemokine receptor paralogs in various mammalian lineages, especially between the cytogenetically closely located pairs CCR2/5 and CCR1/3. Datasets of mammalian orthologs for each gene were analyzed separately to minimize the potential confounding impact of analyzing highly similar sequences resulting from gene conversion events. Molecular evolution approaches and the software package Phylogenetic Analyses by Maximum Likelihood (PAML were utilized to investigate the signature of selection that has acted on the mammalian CC chemokine receptor (CCR gene family. The results of neutral vs. adaptive evolution (positive selection hypothesis testing using Site Models are reported. In general, positive selection is defined by a ratio of nonsynonymous/synonymous nucleotide changes (dN/dS, or ω >1. Results Of the ten mammalian CC motif chemokine receptor sequence datasets analyzed, only CCR2 and CCR3 contain amino acid codon sites that exhibit evidence of positive selection using site based hypothesis testing in PAML. Nineteen of the twenty codon sites putatively indentified as likely to be under positive

Selection and Neutral Mutations Drive Pervasive Mutability Losses in Long-Lived Anti-HIV B-Cell Lineages

Science.gov (United States)

Vieira, Marcos C; Zinder, Daniel; Cobey, Sarah

2018-01-01

Abstract High-affinity antibodies arise within weeks of infection from the evolution of B-cell receptors under selection to improve antigen recognition. This rapid adaptation is enabled by the distribution of highly mutable “hotspot” motifs in B-cell receptor genes. High mutability in antigen-binding regions (complementarity determining regions [CDRs]) creates variation in binding affinity, whereas low mutability in structurally important regions (framework regions [FRs]) may reduce the frequency of destabilizing mutations. During the response, loss of mutational hotspots and changes in their distribution across CDRs and FRs are predicted to compromise the adaptability of B-cell receptors, yet the contributions of different mechanisms to gains and losses of hotspots remain unclear. We reconstructed changes in anti-HIV B-cell receptor sequences and show that mutability losses were ∼56% more frequent than gains in both CDRs and FRs, with the higher relative mutability of CDRs maintained throughout the response. At least 21% of the total mutability loss was caused by synonymous mutations. However, nonsynonymous substitutions caused most (79%) of the mutability loss in CDRs. Because CDRs also show strong positive selection, this result suggests that selection for mutations that increase binding affinity contributed to loss of mutability in antigen-binding regions. Although recurrent adaptation to evolving viruses could indirectly select for high mutation rates, we found no evidence of indirect selection to increase or retain hotspots. Our results suggest mutability losses are intrinsic to both the neutral and adaptive evolution of B-cell populations and might constrain their adaptation to rapidly evolving pathogens such as HIV and influenza. PMID:29688540

Likelihood analysis of the chalcone synthase genes suggests the role of positive selection in morning glories (Ipomoea).

Science.gov (United States)

Yang, Ji; Gu, Hongya; Yang, Ziheng

2004-01-01

Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoides, which are important for the pigmentation of flowers and act as attractants to pollinators. Genes encoding CHS constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. In morning glories (Ipomoea), five functional CHS genes (A-E) have been described. Phylogenetic analysis of the Ipomoea CHS gene family revealed that CHS A, B, and C experienced accelerated rates of amino acid substitution relative to CHS D and E. To examine whether the CHS genes of the morning glories underwent adaptive evolution, maximum-likelihood models of codon substitution were used to analyze the functional sequences in the Ipomoea CHS gene family. These models used the nonsynonymous/synonymous rate ratio (omega = d(N)/ d(S)) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio test suggested significant variation in selection pressure among amino acid sites, with a small proportion of them detected to be under positive selection along the branches ancestral to CHS A, B, and C. Positive Darwinian selection appears to have promoted the divergence of subfamily ABC and subfamily DE and is at least partially responsible for a rate increase following gene duplication.

MDEP Common Position CP-DICWG-07. Common position on selection and use of industrial digital devices of limited functionality

International Nuclear Information System (INIS)

2014-01-01

The nuclear power industry is increasingly interested in using industrial digital devices of limited functionality in systems important to safety, but that have not been developed specifically for use in nuclear power applications. These devices should meet certain specific requirements in order to be selected and used in systems important to safety at nuclear power plants. Typically, some of these devices are found embedded in plant components and actuating devices, e.g. sensing instrumentation, motors, pumps, actuators, breakers. The Digital Instrumentation and Controls Working Group (DICWG) has agreed that a common position on this topic is warranted given the increase of use of Digital I and C in new reactor designs, its safety implications, and the need to develop a common understanding from the perspectives of regulatory authorities. This action follows the DICWG examination of the regulatory requirements of the participating members and of relevant industry standards and IAEA documents. The DICWG proposes a common position based on its recent experience with the new reactor application reviews and operating plant issues

Destabilization of the Outer and Inner Mitochondrial Membranes by Core and Linker Histones

Science.gov (United States)

Cascone, Annunziata; Bruelle, Celine; Lindholm, Dan; Bernardi, Paolo; Eriksson, Ove

2012-01-01

Background Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria. Methodology/Principal Findings We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, and H4 bind strongly to isolated mitochondria. All histones caused a rapid and massive release of the pro-apoptotic intermembrane space proteins cytochrome c and Smac/Diablo, indicating that they permeabilize the outer mitochondrial membrane. In addition, linker histone H1, but not core histones, permeabilized the inner membrane with a collapse of the membrane potential, release of pyridine nucleotides, and mitochondrial fragmentation. Conclusions We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage. PMID:22523586

Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to HER2-positive Breast Cancer Cells in Vitro

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Liu Zhe

2012-07-01

Full Text Available Abstract Background Aptamer-based tumor targeted drug delivery system is a promising approach that may increase the efficacy of chemotherapy and reduce the related toxicity. HER2 protein is an attractive target for tumor-specific drug delivery because of its overexpression in multiple malignancies, including breast, gastric, ovarian, and lung cancers. Methods In this paper, we developed a new HER2 aptamer (HB5 by using systematic evolution of ligands by exponential enrichment technology (SELEX and exploited its role as a targeting ligand for delivering doxorubicin (Dox to breast cancer cells in vitro. Results The selected aptamer was an 86-nucleotide DNA molecule that bound to an epitope peptide of HER2 with a Kd of 18.9 nM. The aptamer also bound to the extracellular domain (ECD of HER2 protein with a Kdof 316 nM, and had minimal cross reactivity to albumin or trypsin. In addition, the aptamer was found to preferentially bind to HER2-positive but not HER2-negative breast cancer cells. An aptamer-doxorubicin complex (Apt-Dox was formulated by intercalating Dox into the DNA structure of HB5. The Apt-Dox complex could selectively deliver Dox to HER2-positive breast cancer cells while reducing the drug intake by HER2-negative cells in vitro. Moreover, Apt-Dox retained the cytotoxicity of Dox against HER2-positive breast cancer cells, but reduced the cytotoxicity to HER2-negative cells. Conclusions The results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive breast cancer cells.

Optimized Reaction Conditions for Removal of Cellular Organic Matter of Microcystis aeruginosa During the Destabilization and Aggregation Process Using Ferric Sulfate in Water Purification

Czech Academy of Sciences Publication Activity Database

Pivokonský, Martin; Polášek, Pavel; Pivokonská, Lenka; Tomášková, Hana

2009-01-01

Roč. 81, č. 5 (2009), s. 514-522 ISSN 1061-4303 R&D Projects: GA ČR GA103/07/0295 Institutional research plan: CEZ:AV0Z20600510 Keywords : Microcystis aeruginosa * cellular organic matter * destabilization * aggregation * optimized reaction conditions * water purification Subject RIV: BK - Fluid Dynamics Impact factor: 0.965, year: 2009

Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

Science.gov (United States)

Botosso, Viviane F; Zanotto, Paolo M de A; Ueda, Mirthes; Arruda, Eurico; Gilio, Alfredo E; Vieira, Sandra E; Stewien, Klaus E; Peret, Teresa C T; Jamal, Leda F; Pardini, Maria I de M C; Pinho, João R R; Massad, Eduardo; Sant'anna, Osvaldo A; Holmes, Eddie C; Durigon, Edison L

2009-01-01

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

Directory of Open Access Journals (Sweden)

Viviane F Botosso

2009-01-01

Full Text Available Human respiratory syncytial virus (HRSV is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

Influence of nucleotide modifications at the C2' position on the Hoogsteen base-paired parallel-stranded duplex of poly(A) RNA.

Science.gov (United States)

Copp, William; Denisov, Alexey Y; Xie, Jingwei; Noronha, Anne M; Liczner, Christopher; Safaee, Nozhat; Wilds, Christopher J; Gehring, Kalle

2017-09-29

Polyadenylate (poly(A)) has the ability to form a parallel duplex with Hoogsteen adenine:adenine base pairs at low pH or in the presence of ammonium ions. In order to evaluate the potential of this structural motif for nucleic acid-based nanodevices, we characterized the effects on duplex stability of substitutions of the ribose sugar with 2'-deoxyribose, 2'-O-methyl-ribose, 2'-deoxy-2'-fluoro-ribose, arabinose and 2'-deoxy-2'-fluoro-arabinose. Deoxyribose substitutions destabilized the poly(A) duplex both at low pH and in the presence of ammonium ions: no duplex formation could be detected with poly(A) DNA oligomers. Other sugar C2' modifications gave a variety of effects. Arabinose and 2'-deoxy-2'-fluoro-arabinose nucleotides strongly destabilized poly(A) duplex formation. In contrast, 2'-O-methyl and 2'-deoxy-2'-fluoro-ribo modifications were stabilizing either at pH 4 or in the presence of ammonium ions. The differential effect suggests they could be used to design molecules selectively responsive to pH or ammonium ions. To understand the destabilization by deoxyribose, we determined the structures of poly(A) duplexes with a single DNA residue by nuclear magnetic resonance spectroscopy and X-ray crystallography. The structures revealed minor structural perturbations suggesting that the combination of sugar pucker propensity, hydrogen bonding, pKa shifts and changes in hydration determine duplex stability. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

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Jimcy Platholi

Full Text Available General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.

Alanine Counteracts the Destabilizing Effect that Urea has on RNase-A.

Science.gov (United States)

Chowhan, Rimpy K; Ali, Fasil; Bhat, Mohd Y; Rahman, Safikur; Singh, Laishram R; Ahmad, Faizan; Dar, Tanveer A

2016-01-01

It is generally believed that organisms use and accumulate methylamine osmolytes to prevent urea's damaging effect on protein stability and activity. However, urea-rich cells not only accumulate methylamines but also many other methylated and non-methylated compounds as well. But, so far it is not known whether osmolytes that are not accumulated in urea-rich cells could also confer urea-counteracting properties. We investigated the behavior of a non-methylamine osmolyte, alanine for its counteracting effect against urea denaturation of a model protein, ribonuclease A (RNase-A). We have measured structure and thermodynamic parameters (Tm, ΔHm, and ΔGD°) of RNase-A in the presence of alanine, urea and their combination. The results were also compared with the ability of glycine (osmolyte lacking one methyl group when compared with alanine) to counter urea's effect on protein stability. We observed that alanine but not glycine counteracts urea's harmful effect on RNase-A stability. The results indicated that alanine (in addition to methylamine osmolytes) may serve as an alternate urea-counteractant. Since glycine fails to protect RNase-A from urea's destabilizing effect, it seems that methylation to glycine might have some evolutionary significance to protect proteins against harmful effects of urea.

Cortisol and testosterone increase financial risk taking and may destabilize markets

Science.gov (United States)

Cueva, Carlos; Roberts, R. Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N.; Herbert, Joe; Rustichini, Aldo

2015-01-01

It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders’ financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways. PMID:26135946

Destabilization of Heterologous Proteins Mediated by the GSK3β Phosphorylation Domain of the β-Catenin Protein

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Yuhan Kong

2013-11-01

Full Text Available Background and Aims: Wnt/β-catenin signaling plays important roles in development and cellular processes. The hallmark of canonical Wnt signaling activation is the stabilization of β-catenin protein in cytoplasm and/or nucleus. The stability of β-catenin is the key to its biological functions and is controlled by the phosphorylation of its amino-terminal degradation domain. Aberrant activation of β-catenin signaling has been implicated in the development of human cancers. It has been recently suggested that GSK3βmay play an essential role in regulating global protein turnover. Here, we investigate if the GSK3β phosphorylation site-containing degradation domain of β-catenin is sufficient to destabilize heterologous proteins. Methods and Results: We engineer chimeric proteins by fusing β-catenin degradation domain at the N- and/or C-termini of the enhanced green fluorescent protein (eGFP. In both transient and stable expression experiments, the chimeric GFP proteins exhibit a significantly decreased stability, which can be effectively antagonized by lithium and Wnt1. An activating mutation in the destruction domain significantly stabilizes the fusion protein. Furthermore, GSK3 inhibitor SB-216763 effectively increases the GFP signal of the fusion protein. Conversely, the inhibition of Wnt signaling with tankyrase inhibitor XAV939 results in a decrease in GFP signal of the fusion proteins, while these small molecules have no significant effects on the mutant destruction domain-GFP fusion protein. Conclusion: Our findings strongly suggest that the β-catenin degradation domain may be sufficient to destabilize heterologous proteins in Wnt signaling-dependent manner. It is conceivable that the chimeric GFP proteins may be used as a functional reporter to measure the dynamic status of β-catenin signaling, and to identify potential anticancer drugs that target β-catenin signaling.

Genes under positive selection in a model plant pathogenic fungus, Botrytis.

Science.gov (United States)

Aguileta, Gabriela; Lengelle, Juliette; Chiapello, Hélène; Giraud, Tatiana; Viaud, Muriel; Fournier, Elisabeth; Rodolphe, François; Marthey, Sylvain; Ducasse, Aurélie; Gendrault, Annie; Poulain, Julie; Wincker, Patrick; Gout, Lilian

2012-07-01

The rapid evolution of particular genes is essential for the adaptation of pathogens to new hosts and new environments. Powerful methods have been developed for detecting targets of selection in the genome. Here we used divergence data to compare genes among four closely related fungal pathogens adapted to different hosts to elucidate the functions putatively involved in adaptive processes. For this goal, ESTs were sequenced in the specialist fungal pathogens Botrytis tulipae and Botrytis ficariarum, and compared with genome sequences of Botrytis cinerea and Sclerotinia sclerotiorum, responsible for diseases on over 200 plant species. A maximum likelihood-based analysis of 642 predicted orthologs detected 21 genes showing footprints of positive selection. These results were validated by resequencing nine of these genes in additional Botrytis species, showing they have also been rapidly evolving in other related species. Twenty of the 21 genes had not previously been identified as pathogenicity factors in B. cinerea, but some had functions related to plant-fungus interactions. The putative functions were involved in respiratory and energy metabolism, protein and RNA metabolism, signal transduction or virulence, similarly to what was detected in previous studies using the same approach in other pathogens. Mutants of B. cinerea were generated for four of these genes as a first attempt to elucidate their functions. Copyright © 2012 Elsevier B.V. All rights reserved.

Multi-scale textural feature extraction and particle swarm optimization based model selection for false positive reduction in mammography.

Science.gov (United States)

Zyout, Imad; Czajkowska, Joanna; Grzegorzek, Marcin

2015-12-01

The high number of false positives and the resulting number of avoidable breast biopsies are the major problems faced by current mammography Computer Aided Detection (CAD) systems. False positive reduction is not only a requirement for mass but also for calcification CAD systems which are currently deployed for clinical use. This paper tackles two problems related to reducing the number of false positives in the detection of all lesions and masses, respectively. Firstly, textural patterns of breast tissue have been analyzed using several multi-scale textural descriptors based on wavelet and gray level co-occurrence matrix. The second problem addressed in this paper is the parameter selection and performance optimization. For this, we adopt a model selection procedure based on Particle Swarm Optimization (PSO) for selecting the most discriminative textural features and for strengthening the generalization capacity of the supervised learning stage based on a Support Vector Machine (SVM) classifier. For evaluating the proposed methods, two sets of suspicious mammogram regions have been used. The first one, obtained from Digital Database for Screening Mammography (DDSM), contains 1494 regions (1000 normal and 494 abnormal samples). The second set of suspicious regions was obtained from database of Mammographic Image Analysis Society (mini-MIAS) and contains 315 (207 normal and 108 abnormal) samples. Results from both datasets demonstrate the efficiency of using PSO based model selection for optimizing both classifier hyper-parameters and parameters, respectively. Furthermore, the obtained results indicate the promising performance of the proposed textural features and more specifically, those based on co-occurrence matrix of wavelet image representation technique. Copyright © 2015 Elsevier Ltd. All rights reserved.

Destabilization of Oil-in-Water Emulsions Formed Using Highly Hydrolyzed Whey Proteins.

Science.gov (United States)

Agboola; Singh; Munro; Dalgleish; Singh

1998-01-19

Oil-in-water emulsions (4 wt % soy oil) were prepared with 0.5-5 wt % whey protein hydrolysate (WPH) (27% degree of hydrolysis), in a two-stage homogenizer using various first-stage pressures of 10.3, 20.6, and 34.3 MPa and a constant second-stage pressure of 3.4 MPa. Destabilization studies on the emulsions were carried out for up to 24 h, using both laser light scattering and confocal laser microscopy. It was found that emulsions formed with oiling off and coalescence at all homogenization pressures. Emulsions formed with 2, 3, and 4% WPH showed coalescence and creaming only, while slight flocculation but no creaming occurred in emulsions formed with 5% WPH. Furthermore, the apparent rate of coalescence increased with homogenization pressure but decreased with WPH concentration. In contrast, the surface concentration of WPH increased with the WPH concentration in the emulsions but decreased with homogenization pressure. Analysis of WPH by high-performance liquid chromatography showed an increase in the concentration of high molecular weight peptides at the droplet surface compared to the WPH solution. This was considered very important for the stability of these oil-in-water emulsions.

Thinking about a limited future enhances the positivity of younger and older adults' recall: Support for socioemotional selectivity theory.

Science.gov (United States)

Barber, Sarah J; Opitz, Philipp C; Martins, Bruna; Sakaki, Michiko; Mather, Mara

2016-08-01

Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the "positivity effect," and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants' recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults' recall is typically more positive than younger adults' recall may index naturally shifting time horizons and goals with age.

Thinking about a Limited Future Enhances the Positivity of Younger and Older Adults’ Recall: Support for Socioemotional Selectivity Theory

Science.gov (United States)

Barber, Sarah J.; Opitz, Philipp C.; Martins, Bruna; Sakaki, Michiko; Mather, Mara

2016-01-01

Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the “positivity effect,” and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants’ recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults’ recall is typically more positive than younger adults’ recall may index naturally shifting time horizons and goals with age. PMID:27112461

Role of maturity timing in selection procedures and in the specialisation of playing positions in youth basketball

NARCIS (Netherlands)

te Wierike, Sanne Cornelia Maria; Elferink-Gemser, Marije Titia; Tromp, Eveline Jenny Yvonne; Vaeyens, Roel; Visscher, Chris

2015-01-01

This study investigated the role of maturity timing in selection procedures and in the specialisation of playing positions in youth male basketball. Forty-three talented Dutch players (14.66 +/- 1.09years) participated in this study. Maturity timing (age at peak height velocity), anthropometric,

Destabilization of the 6H-SrIrO3 polymorph through partial substitution of zinc and lithium

DEFF Research Database (Denmark)

Bremholm, Martin; K. Kim, Cindi; Hirai, Daigo

2012-01-01

We report on the destabilization of the 6H-SrIrO3 polymorph through partial substitutions of zinc and lithium for iridium to form perovskites. The perovskites crystallize in the orthorhombic space group Pbnm: SrIr1−xZnxO3 is found for 0.25 ≤ x ≤ 0.33, while SrIr1−xLixO3 is found only for x = 0...... show Curie–Weiss behavior, with relatively large temperature independent contributions, and that the iridium atoms have low effective moments, 0.52 to 1.08 μB per Ir. The resistivity of SrIr0.67Zn0.33O3, characterized by Mott variable range hopping type semiconducting behavior, indicates...

Flight Results of the NF-15B Intelligent Flight Control System (IFCS) Aircraft with Adaptation to a Longitudinally Destabilized Plant

Science.gov (United States)

Bosworth, John T.

2008-01-01

Adaptive flight control systems have the potential to be resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. The goal for the adaptive system is to provide an increase in survivability in the event that these extreme changes occur. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane. The adaptive element was incorporated into a dynamic inversion controller with explicit reference model-following. As a test the system was subjected to an abrupt change in plant stability simulating a destabilizing failure. Flight evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to stabilize the vehicle and reestablish good onboard reference model-following. Flight evaluation with the simulated destabilizing failure and adaptation engaged showed improvement in the vehicle stability margins. The convergent properties of this initial system warrant additional improvement since continued maneuvering caused continued adaptation change. Compared to the non-adaptive system the adaptive system provided better closed-loop behavior with improved matching of the onboard reference model. A detailed discussion of the flight results is presented.

Signatures of positive selection in African Butana and Kenana dairy zebu cattle.

Science.gov (United States)

Bahbahani, Hussain; Salim, Bashir; Almathen, Faisal; Al Enezi, Fahad; Mwacharo, Joram M; Hanotte, Olivier

2018-01-01

Butana and Kenana are two types of zebu cattle found in Sudan. They are unique amongst African indigenous zebu cattle because of their high milk production. Aiming to understand their genome structure, we genotyped 25 individuals from each breed using the Illumina BovineHD Genotyping BeadChip. Genetic structure analysis shows that both breeds have an admixed genome composed of an even proportion of indicine (0.75 ± 0.03 in Butana, 0.76 ± 0.006 in Kenana) and taurine (0.23 ± 0.009 in Butana, 0.24 ± 0.006 in Kenana) ancestries. We also observe a proportion of 0.02 to 0.12 of European taurine ancestry in ten individuals of Butana that were sampled from cattle herds in Tamboul area suggesting local crossbreeding with exotic breeds. Signatures of selection analyses (iHS and Rsb) reveal 87 and 61 candidate positive selection regions in Butana and Kenana, respectively. These regions span genes and quantitative trait loci (QTL) associated with biological pathways that are important for adaptation to marginal environments (e.g., immunity, reproduction and heat tolerance). Trypanotolerance QTL are intersecting candidate regions in Kenana cattle indicating selection pressure acting on them, which might be associated with an unexplored level of trypanotolerance in this cattle breed. Several dairy traits QTL are overlapping the identified candidate regions in these two zebu cattle breeds. Our findings underline the potential to improve dairy production in the semi-arid pastoral areas of Africa through breeding improvement strategy of indigenous local breeds.

Lithosphere destabilization by melt percolation during pre-oceanic rifting: Evidence from Alpine-Apennine ophiolitic peridotites

Science.gov (United States)

Piccardo, Giovanni; Ranalli, Giorgio

2017-04-01

conditions. This indicates that thermal advection by percolation of hot asthenospheric melts significantly heated the lithospheric mantle column above the melting asthenosphere. Numerical and analogue models show that infiltration of melts results in considerable softening of mantle rocks. Total ithospheric strength can be decreased from 10 to 1 TN m-1 as orders of magnitude and the sin-rift thermo-mechanical erosion of the lithospheric mantle induces significant rheological softening along the axial zone of extension (Corti et al., 2007; Ranalli et al., 2007). Softening of the lithospheric mantle may lead to whole lithospheric failure and consequently to transition from continental extension to oceanic spreading. Therefore, rheological softening caused destabilization of the lithospheric mantle between the future continental margins (Piccardo et al., 2014; Piccardo, 2016) of the Ligurian Tethys. The wedge of destabilized lithosphere favored faster divergence of the continental blocks and enhanced doming and thermal buoyancy of deeper/hotter asthenosphere that rose between the future continental margins and originated aggregated MORB melts (i.e., the oceanic magmatism that formed olivine-gabbro intrusions and pillowed basalt extrusions). Lithosphere destabilization by melt percolation can play a fundamental role in the geodynamic evolution of lithosphere extension causing transition from continental extension to continental break-up to oceanic spreading. Corti, G., Bonini, M., Innocenti, F., Manetti, P., Piccardo, G.B., Ranalli, G., 2007. Journal of Geodynamics, 43, 465-483. Piccardo, G.B., Padovano, M., Guarnieri, L. 2014. Earth-Science Reviews, 138, 409-434. Piccardo, G.B., 2016. Gondwana Research, 39, 230-249. Piccardo, G.B., Vissers, R.L.M., 2007. Journal of Geodynamics, 43, 417-449. Piccardo, G.B., Guarnieri, L., 2011. Lithos, 124, 210-214. Ranalli, G., Piccardo, G.B., Corona-Chavez, P., 2007. Journal of Geodynamics, 43, 450-464.

Examination of Signatures of Recent Positive Selection on Genes Involved in Human Sialic Acid Biology.

Science.gov (United States)

Moon, Jiyun M; Aronoff, David M; Capra, John A; Abbot, Patrick; Rokas, Antonis

2018-03-28

Sialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that

Detecting loci under recent positive selection in dairy and beef cattle by combining different genome-wide scan methods.

Directory of Open Access Journals (Sweden)

Yuri Tani Utsunomiya

Full Text Available As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP data generated from dairy and beef cattle (taurine and indicine. The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10(-7 population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3 in Brown Swiss (P = 3.82×10(-12, and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.

Evolution of species-specific major seminal fluid proteins in placental mammals by gene death and positive selection

NARCIS (Netherlands)

Meslin, C.; Laurin, M.; Callebaut, I.; Druart, X.; Monget, P.

2015-01-01

The seminal fluid is a complex substance composed of a variety of secreted proteins and has been shown to play an important role in the fertilisation process in mammals and also in Drosophila. Several genes under positive selection have been documented in some rodents and primates. Our study

Intrinsic Toxin-Derived Peptides Destabilize and Inactivate Clostridium difficile TcdB

Directory of Open Access Journals (Sweden)

Jason L. Larabee

2017-05-01

Full Text Available Clostridium difficile infection (CDI is a major cause of hospital-associated, antibiotic-induced diarrhea, which is largely mediated by the production of two large multidomain clostridial toxins, TcdA and TcdB. Both toxins coordinate the action of specific domains to bind receptors, enter cells, and deliver a catalytic fragment into the cytosol. This results in GTPase inactivation, actin disassembly, and cytotoxicity. TcdB in particular has been shown to encode a region covering amino acids 1753 to 1851 that affects epitope exposure and cytotoxicity. Surprisingly, studies here show that several peptides derived from this region, which share the consensus sequence 1769NVFKGNTISDK1779, protect cells from the action of TcdB. One peptide, PepB2, forms multiple interactions with the carboxy-terminal region of TcdB, destabilizes TcdB structure, and disrupts cell binding. We further show that these effects require PepB2 to form a higher-order polymeric complex, a process that requires the central GN amino acid pair. These data suggest that TcdB1769–1779 interacts with repeat sequences in the proximal carboxy-terminal domain of TcdB (i.e., the CROP domain to alter the conformation of TcdB. Furthermore, these studies provide insights into TcdB structure and functions that can be exploited to inactivate this critical virulence factor and ameliorate the course of CDI.

Positive selection on the nonhomologous end-joining factor Cernunnos-XLF in the human lineage

Directory of Open Access Journals (Sweden)

Jurka Jerzy

2006-06-01

Full Text Available Abstract Background Cernunnos-XLF is a nonhomologous end-joining factor that is mutated in patients with a rare immunodeficiency with microcephaly. Several other microcephaly-associated genes such as ASPM and microcephalin experienced recent adaptive evolution apparently linked to brain size expansion in humans. In this study we investigated whether Cernunnos-XLF experienced similar positive selection during human evolution. Results We obtained or reconstructed full-length coding sequences of chimpanzee, rhesus macaque, canine, and bovine Cernunnos-XLF orthologs from sequence databases and sequence trace archives. Comparison of coding sequences revealed an excess of nonsynonymous substitutions consistent with positive selection on Cernunnos-XLF in the human lineage. The hotspots of adaptive evolution are concentrated around a specific structural domain, whose analogue in the structurally similar XRCC4 protein is involved in binding of another nonhomologous end-joining factor, DNA ligase IV. Conclusion Cernunnos-XLF is a microcephaly-associated locus newly identified to be under adaptive evolution in humans, and possibly played a role in human brain expansion. We speculate that Cernunnos-XLF may have contributed to the increased number of brain cells in humans by efficient double strand break repair, which helps to prevent frequent apoptosis of neuronal progenitors and aids mitotic cell cycle progression. Reviewers This article was reviewed by Chris Ponting and Richard Emes (nominated by Chris Ponting, Kateryna Makova, Gáspár Jékely and Eugene V. Koonin.

Population genetic evidence for positive and purifying selection acting at the human IFN-γ locus in Africa.

Science.gov (United States)

Campbell, Michael C; Smith, Lunden T; Harvey, Jayla

2018-03-29

Despite its critical role in the defense against microbial infection and tumor development, little is known about the range of nucleotide and haplotype variation at IFN-γ, or the evolutionary forces that have shaped patterns of diversity at this locus. To address this gap in knowledge, we examined sequence data from the IFN-γ gene in 1461 individuals from 15 worldwide populations. Our analyses uncovered novel patterns of variation in distinct African populations, including an excess of high frequency-derived alleles, unusually long haplotype structure surrounding the IFN-γ gene, and a "star-like" genealogy of African-specific haplotypes carrying variants previously associated with infectious disease. We also inferred a deep time to coalescence of variation at IFN-γ (~ 0.8 million years ago) and ancient ages for common polymorphisms predating the evolution of modern humans. Taken together, these results are congruent with a model of positive selection on standing variation in African populations. Furthermore, we inferred that common variants in intron 3 of IFN-γ are the likely targets of selection. In addition, we observed a paucity of non-synonymous substitutions relative to synonymous changes in the exons of IFN-γ in African and non-African populations, suggestive of strong purifying selection. Therefore, we contend that positive and purifying selection have influenced levels of diversity in different regions of IFN-γ, implying that these distinct genic regions are, or have been, functionally important. Overall, this study provides additional insights into the evolutionary events that have contributed to the frequency and distribution of alleles having a role in human health and disease.

Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery

International Nuclear Information System (INIS)

Brown, Nicole; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

2006-01-01

Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effects of DES on T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8 + T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8 + T cells. The density of expression of HY-TCR on CD8 + cells was increased following DES exposure in both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery

Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery

Energy Technology Data Exchange (ETDEWEB)

Brown, Nicole [Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 (United States); Nagarkatti, Mitzi [Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 (United States); Nagarkatti, Prakash S [Department of Pharmacology and Toxicology, PO Box 980613, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0613 (United States)

2006-04-15

Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effects of DES on T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8{sup +} T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8{sup +} T cells. The density of expression of HY-TCR on CD8{sup +} cells was increased following DES exposure in both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery.

The surface destabilization effect of nitrate on the calcite (104). Water interface and yttrium(III) sorption thereon

Energy Technology Data Exchange (ETDEWEB)

Hellebrandt, S.E.; Hofmann, Sascha; Schmidt, Moritz [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Div. Surface Processes; Stubbs, J.E.; Eng, P.J. [Chicago Univ., IL (United States). Center for Advanced Radiation Sources; Stumpf, Thorsten [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Inst. of Resource Ecology

2016-07-01

Calcite, as a most abundant mineral on earth, was studied with X-ray reflectivity under the influence of NaNO{sub 3} [1]. The calcite (104) surface undergoes significant destabilization effects in the presence of NaNO{sub 3}, which occurs as partial dissolution and the formation of an amorphous layer at the interface. The disordering of the surface reaches more than 15 Aa into the crystal bulk. Furthermore, this surface modification has also an effect on the sorption behavior of the rare earth element Y. Without NaNO{sub 3} Y{sup 3+} adsorbs as both inner and outer sphere complexes, this was verified with resonant anomalous X-ray reflectivity (RAXR). If NaNO{sub 3} is present, both species desorbs from the surface completely.

Positive allometry and the prehistory of sexual selection

OpenAIRE

Tomkins, Joseph L.; LeBas, Natasha R.; Witton, Mark P.; Martill, David M.; Humphries, Stuart

2010-01-01

The function of the exaggerated structures that adorn many fossil vertebrates remains largely unresolved. One recurrent hypothesis is that these elaborated traits had a role in thermoregulation. This orthodoxy persists despite the observation that traits exaggerated to the point of impracticality in extant organisms are almost invariably sexually selected. We use allometric scaling to investigate the role of sexual selection and thermoregulation in the evolution of exaggerated traits of the c...

SU-G-BRC-13: Model Based Classification for Optimal Position Selection for Left-Sided Breast Radiotherapy: Free Breathing, DIBH, Or Prone

Energy Technology Data Exchange (ETDEWEB)

Lin, H; Liu, T; Xu, X [Rensselaer Polytechnic Institute, Troy, NY (United States); Shi, C [Saint Vincent Medical Center, Bridgeport, CT (United States); Petillion, S; Kindts, I [University Hospitals Leuven, Leuven, Vlaams-Brabant (Belgium); Tang, X [Memorial Sloan Kettering Cancer Center, West Harrison, NY (United States)

2016-06-15

Purpose: There are clinical decision challenges to select optimal treatment positions for left-sided breast cancer patients—supine free breathing (FB), supine Deep Inspiration Breath Hold (DIBH) and prone free breathing (prone). Physicians often make the decision based on experiences and trials, which might not always result optimal OAR doses. We herein propose a mathematical model to predict the lowest OAR doses among these three positions, providing a quantitative tool for corresponding clinical decision. Methods: Patients were scanned in FB, DIBH, and prone positions under an IRB approved protocol. Tangential beam plans were generated for each position, and OAR doses were calculated. The position with least OAR doses is defined as the optimal position. The following features were extracted from each scan to build the model: heart, ipsilateral lung, breast volume, in-field heart, ipsilateral lung volume, distance between heart and target, laterality of heart, and dose to heart and ipsilateral lung. Principal Components Analysis (PCA) was applied to remove the co-linearity of the input data and also to lower the data dimensionality. Feature selection, another method to reduce dimensionality, was applied as a comparison. Support Vector Machine (SVM) was then used for classification. Thirtyseven patient data were acquired; up to now, five patient plans were available. K-fold cross validation was used to validate the accuracy of the classifier model with small training size. Results: The classification results and K-fold cross validation demonstrated the model is capable of predicting the optimal position for patients. The accuracy of K-fold cross validations has reached 80%. Compared to PCA, feature selection allows causal features of dose to be determined. This provides more clinical insights. Conclusion: The proposed classification system appeared to be feasible. We are generating plans for the rest of the 37 patient images, and more statistically significant

Destabilization of hydromagnetic drift-Alfven waves in a finite pressure collisional plasma

International Nuclear Information System (INIS)

Tang, J.T.

1974-01-01

In a finite beta (β = 8πn 0 kT 0 /B 0 2 ) plasma, where the plasma pressure n 0 kT 0 is an appreciable fraction of the confining magnetic field energy-density B 0 2 /8π, density-gradient driven drift waves couple with Alfven waves when the phase velocities of the two waves become comparable. The resulting hydromagnetic drift-Alfven waves separate into two branches--a drift mode and an Alfven mode, with both modes exhibiting magnetic field and localized density fluctuations near the coupling point. The dispersion relation of the collisional drift-Alfven wave is derived by using a slab-geometry, two-fluid model which includes finite beta, electron-ion collisions, ion-ion collisions, finite ion larmar radius, temperature fluctuations, and an axial electron current. A hydromagnetic drift mode is found to be unstable in a moderately dense plasma. A localized ''Alfven'' mode is destabilized only with the passage of an axial current along the plasma column. In order to check the theoretical predictions an experiment is performed in a finite-beta plasma of density n 0 = 10 13 -10 15 cm -3 and temperature T/sub e/ approximately T/sub i/ = 1-7 eV. (U.S.)

Positive Selection Drives the Evolution of rhino, a Member of the Heterochromatin Protein 1 Family in Drosophila.

Directory of Open Access Journals (Sweden)

2005-07-01

Full Text Available Heterochromatin comprises a significant component of many eukaryotic genomes. In comparison to euchromatin, heterochromatin is gene poor, transposon rich, and late replicating. It serves many important biological roles, from gene silencing to accurate chromosome segregation, yet little is known about the evolutionary constraints that shape heterochromatin. A complementary approach to the traditional one of directly studying heterochromatic DNA sequence is to study the evolution of proteins that bind and define heterochromatin. One of the best markers for heterochromatin is the heterochromatin protein 1 (HP1, which is an essential, nonhistone chromosomal protein. Here we investigate the molecular evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas HP1D/rhino and HP1E are expressed predominantly in ovaries and testes respectively. The HP1 paralogs also have distinct localization preferences in Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9 dimethylated H3. Using molecular evolution and population genetic analyses, we find that rhino has been subject to positive selection in all three domains of the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain, and the hinge region that connects these two modules. Maximum likelihood analysis of rhino sequences from 20 species of Drosophila reveals that a small number of residues of the chromo and shadow domains have been subject to repeated positive selection. The rapid and positive selection of rhino is highly unusual for a gene encoding a chromosomal protein and suggests that rhino is involved in a genetic conflict that affects the germline, belying the notion that heterochromatin is simply a passive recipient of "junk DNA" in eukaryotic genomes.

Positive selection drives the evolution of rhino, a member of the heterochromatin protein 1 family in Drosophila.

Directory of Open Access Journals (Sweden)

Danielle Vermaak

2005-07-01

Full Text Available Heterochromatin comprises a significant component of many eukaryotic genomes. In comparison to euchromatin, heterochromatin is gene poor, transposon rich, and late replicating. It serves many important biological roles, from gene silencing to accurate chromosome segregation, yet little is known about the evolutionary constraints that shape heterochromatin. A complementary approach to the traditional one of directly studying heterochromatic DNA sequence is to study the evolution of proteins that bind and define heterochromatin. One of the best markers for heterochromatin is the heterochromatin protein 1 (HP1, which is an essential, nonhistone chromosomal protein. Here we investigate the molecular evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas HP1D/rhino and HP1E are expressed predominantly in ovaries and testes respectively. The HP1 paralogs also have distinct localization preferences in Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9 dimethylated H3. Using molecular evolution and population genetic analyses, we find that rhino has been subject to positive selection in all three domains of the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain, and the hinge region that connects these two modules. Maximum likelihood analysis of rhino sequences from 20 species of Drosophila reveals that a small number of residues of the chromo and shadow domains have been subject to repeated positive selection. The rapid and positive selection of rhino is highly unusual for a gene encoding a chromosomal protein and suggests that rhino is involved in a genetic conflict that affects the germline, belying the notion that heterochromatin is simply a passive recipient of "junk DNA" in eukaryotic genomes.

Selecting Candidates for Key Leadership Positions in Program Executive Offices Ground Combat Systems and Combat Service and Combat Service Support

Science.gov (United States)

2016-10-14

start or continue a profitable growth pattern and boost morale and motivation, a poor decision may bring the company to the brink of financial...HON Frank Kendall issued a memorandum titled “Key Leadership Positions and Qualification Criteria” (Kendall, 2013). This memorandum provides a...Chief Developmental Tester • Program Lead, Business Financial Manager SELECTING CANDIDATES FOR KEY LEADERSHIP POSITIONS 4

Lineage-specific positive selection at the merozoite surface protein 1 (msp1 locus of Plasmodium vivax and related simian malaria parasites

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Kawai Satoru

2010-02-01

Full Text Available Abstract Background The 200 kDa merozoite surface protein 1 (MSP-1 of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. Plasmodium vivax, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to P. vivax-related malaria parasites greatly differ among host species (albeit other factors. It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity. Results We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (msp1 from P. vivax and nine P. vivax-related simian malaria parasites. The inferred phylogenetic tree of msp1 significantly differed from that of the mitochondrial genome, with a striking displacement of P. vivax from a position close to P. cynomolgi in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to P. inui and P. hylobati and the other leading to P. vivax, P. fieldi and P. cynomolgi. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of msp1 polymorphisms between P. vivax, P. inui and P. cynomolgi revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species

Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

Science.gov (United States)

van der Crabben, Saskia N.; Hennus, Marije P.; McGregor, Grant A.; Ritter, Deborah I.; Nagamani, Sandesh C.S.; Wells, Owen S.; Harakalova, Magdalena; Chinn, Ivan K.; Alt, Aaron; Vondrova, Lucie; Hochstenbach, Ron; van Montfrans, Joris M.; Terheggen-Lagro, Suzanne W.; van Lieshout, Stef; van Roosmalen, Markus J.; Renkens, Ivo; Duran, Karen; Nijman, Isaac J.; Kloosterman, Wigard P.; Hennekam, Eric; van Hasselt, Peter M.; Wheeler, David A.; Palecek, Jan J.; Lehmann, Alan R.; Oliver, Antony W.; Pearl, Laurence H.; Plon, Sharon E.; Murray, Johanne M.

2016-01-01

The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood. PMID:27427983

Promotion of selective pathways in isomerizing functionalization of plant oils by rigid framework substituents

KAUST Repository

Christl, Josefine T.

2014-10-14

The 1,2-(CH2P(1-adamantyl)2)2C6H4 (dadpx) coordinated palladium complex [(dadpx)Pd(OTf)2] (1) is a catalyst precursor for the isomerizing methoxycarbonylation of the internal double bond of methyl oleate, with an unprecedented selectivity (96%) for the linear diester 1,19-dimethyl nonadecanedioate. Rapid formation of the catalytically active solvent-coordinated hydride species [(dadpx)PdH(MeOH)]+ (3-MeOH) is evidenced by NMR spectroscopy, and further isolation and X-ray crystal structure analysis of [(dadpx)PdH(PPh3)]+ (3-PPh3). DFT calculations of key steps of the catalytic cycle unravel methanolysis as the decisive step for enhanced selectivity and the influence of the rigid adamantyl framework on this step by destabilization of transition states of unselective pathways.

Breast conservation therapy based on liberal selection criteria and less extensive surgery. Analysis of cases with positive margins

International Nuclear Information System (INIS)

Amemiya, Atsushi; Kondo, Makoto

1999-01-01

The relationship between the margin status and the risk of in-breast recurrence (IBR) is an important consideration in patients treated with breast conservation therapy but has not been defined adequately. To address this issue, 1533 clinical stage I and II patients who completed irradiation therapy between 1983 and 1998 were evaluated. Only selection criterion was whether she could be satisfied with cosmesis after lumpectomy. Size and location of the tumor, nodal status, histology and age were not primary consideration. The tumor was excised in such a way to obtain macroscopically clear margins. The breast was treated with 50 Gy of external irradiation but without boost. Margins were evaluated by serially sectioning of the specimen and the margin was judged positive only when cancer cells were present on the inked surface. Margins were also evaluated by scratch cytology. Seventy two IBR were experienced within 5 years. Only age and margin status were found to be independent risk factors. Five-year IBR rate with negative and positive margins was 3.7% and 10.0%, respectively. In patients with positive margins, number of positive site and positive cytology were independent risk factor for IBR. IBR rate among patients with focally involved margins by non-comedo, comedo and invasive ca, was 0.0%, 3.5%, and 8.7%, respectively. IBR rate in more than focal involvement by non-comedo, comedo, and invasive ca, was 4.0%, 33.0% and 30.0%, respectively. If histologically positive margin was also positive cytologically, IBR was 14.8%, whereas only 3.6% if negative cytologically. Even with liberal patient selection and less extensive local treatment, adequate local control can be obtained, provided that margins are histologically and/or cytologically negative. Focal margin involvement by DCIS or more than focal involvement by non-comedo type DCIS does not jeopardize local control. More than focal involvement by comedo DCIS or involvement by invasive ca results in high IBR rate

Age-dependent Changes in the Articular Cartilage and Subchondral Bone of C57BL/6 Mice after Surgical Destabilization of Medial Meniscus.

Science.gov (United States)

Huang, Henry; Skelly, Jordan D; Ayers, David C; Song, Jie

2017-02-09

Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and μCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research.

Age-dependent Changes in the Articular Cartilage and Subchondral Bone of C57BL/6 Mice after Surgical Destabilization of Medial Meniscus

Science.gov (United States)

Huang, Henry; Skelly, Jordan D.; Ayers, David C.; Song, Jie

2017-01-01

Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and μCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research. PMID:28181577

Distinction of Gram-positive and -negative bacteria using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium salts with a selection medium.

Science.gov (United States)

Tsukatani, Tadayuki; Suenaga, Hikaru; Higuchi, Tomoko; Shiga, Masanobu; Noguchi, Katsuya; Matsumoto, Kiyoshi

2011-01-01

Bacteria are fundamentally divided into two groups: Gram-positive and Gram-negative. Although the Gram stain and other techniques can be used to differentiate these groups, some issues exist with traditional approaches. In this study, we developed a method for differentiating Gram-positive and -negative bacteria using a colorimetric microbial viability assay based on the reduction of the tetrazolium salt {2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt} (WST-8) via 2-methyl-1,4-napthoquinone with a selection medium. We optimized the composition of the selection medium to allow the growth of Gram-negative bacteria while inhibiting the growth of Gram-positive bacteria. When the colorimetric viability assay was carried out in a selection medium containing 0.5µg/ml crystal violet, 5.0 µg/ml daptomycin, and 5.0µg/ml vancomycin, the reduction in WST-8 by Gram-positive bacteria was inhibited. On the other hand, Gram-negative bacteria produced WST-8-formazan in the selection medium. The proposed method was also applied to determine the Gram staining characteristics of bacteria isolated from various foodstuffs. There was good agreement between the results obtained using the present method and those obtained using a conventional staining method. These results suggest that the WST-8 colorimetric assay with selection medium is a useful technique for accurately differentiating Gram-positive and -negative bacteria.

Physicochemical evolution and positive selection of the ...

Indian Academy of Sciences (India)

2010-04-08

Apr 8, 2010 ... It is not clear whether matK evolves under Darwinian selection. In this study, the gymnosperm Taxaceae, Cephalotaxaceae and Pinaceae were used to illustrate the physicochemical evolution, molecular adaptation and evolutionary dynamics of gene divergence in matKs. matK sequences were amplified ...

Positive selection of a duplicated UV-sensitive visual pigment coincides with wing pigment evolution in Heliconius butterflies

Science.gov (United States)

Briscoe, Adriana D.; Bybee, Seth M.; Bernard, Gary D.; Yuan, Furong; Sison-Mangus, Marilou P.; Reed, Robert D.; Warren, Andrew D.; Llorente-Bousquets, Jorge; Chiao, Chuan-Chin

2010-01-01

The butterfly Heliconius erato can see from the UV to the red part of the light spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain three visual pigments, rhodopsins, produced by an 11-cis-3-hydroxyretinal chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1) opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)—a previously undescribed duplication of this gene among Lepidoptera. To investigate its evolutionary origin, we screened eye cDNAs from 14 butterfly species in the subfamily Heliconiinae and found both copies only among Heliconius. Phylogeny-based tests of selection indicate positive selection of UVRh2 following duplication, and some of the positively selected sites correspond to vertebrate visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two UV-absorbing rhodopsins in the H. erato eye with λmax = 355 nm and 398 nm. Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL-kynurenine (3-OHK)-based yellow wing pigments not found in close relatives. Visual models of how butterflies perceive wing color variation indicate this has resulted in an expansion of the number of distinguishable yellow colors on Heliconius wings. Functional diversification of the UV-sensitive visual pigments may help explain why the yellow wing pigments of Heliconius are so colorful in the UV range compared to the yellow pigments of close relatives lacking the UV opsin duplicate. PMID:20133601

Streamwise vortices destabilize swimming bluegill sunfish (Lepomis macrochirus).

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Maia, Anabela; Sheltzer, Alex P; Tytell, Eric D

2015-03-01

In their natural environment, fish must swim stably through unsteady flows and vortices, including vertical vortices, typically shed by posts in a flow, horizontal cross-flow vortices, often produced by a step or a waterfall in a stream, and streamwise vortices, where the axis of rotation is aligned with the direction of the flow. Streamwise vortices are commonly shed by bluff bodies in streams and by ships' propellers and axial turbines, but we know little about their effects on fish. Here, we describe how bluegill sunfish use more energy and are destabilized more often in flow with strong streamwise vorticity. The vortices were created inside a sealed flow tank by an array of four turbines with similar diameter to the experimental fish. We measured oxygen consumption for seven sunfish swimming at 1.5 body lengths (BL) s(-1) with the turbines rotating at 2 Hz and with the turbines off (control). Simultaneously, we filmed the fish ventrally and recorded the fraction of time spent maneuvering side-to-side and accelerating forward. Separately, we also recorded lateral and ventral video for a combination of swimming speeds (0.5, 1.5 and 2.5 BL s(-1)) and turbine speeds (0, 1, 2 and 3 Hz), immediately after turning the turbines on and 10 min later to test for accommodation. Bluegill sunfish are negatively affected by streamwise vorticity. Spills (loss of heading), maneuvers and accelerations were more frequent when the turbines were on than in the control treatment. These unsteady behaviors, particularly acceleration, correlated with an increase in oxygen consumption in the vortex flow. Bluegill sunfish are generally fast to recover from roll perturbations and do so by moving their pectoral fins. The frequency of spills decreased after the turbines had run for 10 min, but was still markedly higher than in the control, showing that fish partially adapt to streamwise vorticity, but not completely. Coping with streamwise vorticity may be an important energetic

A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.

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Tannistha Nandi

2010-04-01

Full Text Available Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence". To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp, a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%, distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.

Impact of selected troposphere models on Precise Point Positioning convergence

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Kalita, Jakub; Rzepecka, Zofia

2016-04-01

The Precise Point Positioning (PPP) absolute method is currently intensively investigated in order to reach fast convergence time. Among various sources that influence the convergence of the PPP, the tropospheric delay is one of the most important. Numerous models of tropospheric delay are developed and applied to PPP processing. However, with rare exceptions, the quality of those models does not allow fixing the zenith path delay tropospheric parameter, leaving difference between nominal and final value to the estimation process. Here we present comparison of several PPP result sets, each of which based on different troposphere model. The respective nominal values are adopted from models: VMF1, GPT2w, MOPS and ZERO-WET. The PPP solution admitted as reference is based on the final troposphere product from the International GNSS Service (IGS). The VMF1 mapping function was used for all processing variants in order to provide capability to compare impact of applied nominal values. The worst case initiates zenith wet delay with zero value (ZERO-WET). Impact from all possible models for tropospheric nominal values should fit inside both IGS and ZERO-WET border variants. The analysis is based on data from seven IGS stations located in mid-latitude European region from year 2014. For the purpose of this study several days with the most active troposphere were selected for each of the station. All the PPP solutions were determined using gLAB open-source software, with the Kalman filter implemented independently by the authors of this work. The processing was performed on 1 hour slices of observation data. In addition to the analysis of the output processing files, the presented study contains detailed analysis of the tropospheric conditions for the selected data. The overall results show that for the height component the VMF1 model outperforms GPT2w and MOPS by 35-40% and ZERO-WET variant by 150%. In most of the cases all solutions converge to the same values during first

Autonomous site selection and instrument positioning for sample acquisition

Science.gov (United States)

Shaw, A.; Barnes, D.; Pugh, S.

The European Space Agency Aurora Exploration Program aims to establish a European long-term programme for the exploration of Space, culminating in a human mission to space in the 2030 timeframe. Two flagship missions, namely Mars Sample Return and ExoMars, have been proposed as recognised steps along the way. The Exomars Rover is the first of these flagship missions and includes a rover carrying the Pasteur Payload, a mobile exobiology instrumentation package, and the Beagle 2 arm. The primary objective is the search for evidence of past or present life on mars, but the payload will also study the evolution of the planet and the atmosphere, look for evidence of seismological activity and survey the environment in preparation for future missions. The operation of rovers in unknown environments is complicated, and requires large resources not only on the planet but also in ground based operations. Currently, this can be very labour intensive, and costly, if large teams of scientists and engineers are required to assess mission progress, plan mission scenarios, and construct a sequence of events or goals for uplink. Furthermore, the constraints in communication imposed by the time delay involved over such large distances, and line-of-sight required, make autonomy paramount to mission success, affording the ability to operate in the event of communications outages and be opportunistic with respect to scientific discovery. As part of this drive to reduce mission costs and increase autonomy the Space Robotics group at the University of Wales, Aberystwyth is researching methods of autonomous site selection and instrument positioning, directly applicable to the ExoMars mission. The site selection technique used builds on the geometric reasoning algorithms used previously for localisation and navigation [Shaw 03]. It is proposed that a digital elevation model (DEM) of the local surface, generated during traverse and without interaction from ground based operators, can be

Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract.

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Li, Jinxing; Thamphiwatana, Soracha; Liu, Wenjuan; Esteban-Fernández de Ávila, Berta; Angsantikul, Pavimol; Sandraz, Elodie; Wang, Jianxing; Xu, Tailin; Soto, Fernando; Ramez, Valentin; Wang, Xiaolei; Gao, Weiwei; Zhang, Liangfang; Wang, Joseph

2016-09-22

The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to a particular location via dissolution of their enteric coating to activate their propulsion at the target site toward localized tissue penetration and retention.

Understanding the connection between epigenetic DNA methylation and nucleosome positioning from computer simulations.

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Guillem Portella

Full Text Available Cytosine methylation is one of the most important epigenetic marks that regulate the process of gene expression. Here, we have examined the effect of epigenetic DNA methylation on nucleosomal stability using molecular dynamics simulations and elastic deformation models. We found that methylation of CpG steps destabilizes nucleosomes, especially when these are placed in sites where the DNA minor groove faces the histone core. The larger stiffness of methylated CpG steps is a crucial factor behind the decrease in nucleosome stability. Methylation changes the positioning and phasing of the nucleosomal DNA, altering the accessibility of DNA to regulatory proteins, and accordingly gene functionality. Our theoretical calculations highlight a simple physical-based explanation on the foundations of epigenetic signaling.

Plasma position control device

International Nuclear Information System (INIS)

Takase, Haruhiko.

1987-01-01

Purpose: To conduct position control stably to various plasmas and reduce the burden on the control coil power source. Constitution: Among the proportional, integration and differentiation controls, a proportional-differentiation control section and an integration control section are connected in parallel. Then, a signal switching circuit is disposed to the control signal input section for the proportional-differentiation control section such that either a present position of plasmas or deviation between the present plasma position and an aimed value can be selected as a control signal depending on the control procedures or the state of the plasmas. For instance, if a rapid response is required for the control, the deviation between the present plasma position and the aimed value is selected as the input signal to conduct proportional, integration and differentiation controls. While on the other hand, if it is intended to reduce the burden on the control coil power source, it is adapted such that the control signal inputted to the proportional-differentiation control section itself can select the present plasma position. (Yoshihara, H.)

Plant operator selection system for evaluating employment candidates' potential for success in electric power plant operations positions

International Nuclear Information System (INIS)

Dunnette, M.D.

1982-01-01

The Plant Operator Selection System is a battery of tests and questionnaires that can be administered to job candidates in less than three hours. Various components of the battery measure what a job candidate has accomplished in previous educational and work situations, how well a candidate compares with others on a number of important aptitudes or abilities, and whether or not a candidate possesses the kind of personal stability required in power plant operations positions. A job candidate's answers to the tests and questionnaires of the Plant Operator Selection System are scored and converted to an OVERALL POTENTIAL INDEX. Values of the OVERALL POTENTIAL INDEX [OPI] range between 0 and 15. Candidates with high OPI values are much more likely to become effective and successful plant operators than candidates with low OPI values. It is possible to estimate the financial advantages to a company of using the Plant Operator Selection System in evaluating candidates for plant operations jobs

Meta-analysis of age and skill effects on recalling chess positions and selecting the best move.

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Moxley, Jerad H; Charness, Neil

2013-10-01

A meta-analysis was conducted of studies that measured the effects of both age and skill in chess on the tasks of selecting the best move for chess positions (the best move task) as well as recalling chess game positions (the recall task). Despite a small sample of studies, we demonstrated that there are age and skill effects on both tasks: age being negatively associated with performance on both tasks and skill being positively associated with performance on both tasks. On the best move task, we found that skill was the dominant effect, while on the recall task, skill and age were approximately equally strong effects. We also found that skill was best measured by the best move task. In the case of the best move task, this result is consistent with the argument that it accurately replicates expert performance (Ericsson & Smith, 1991). Results for the recall task argue that this task captures effects related to skill, but also effects likely due to a general aging process. Implications for our understanding of aging in skilled domains are also discussed.

Insight into destabilization mechanism of Mg-based hydrides interstitially co-doped with nonmetals: a DFT study

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Wu, Zhen; Zhu, Luying; Yang, Fusheng; Zhang, Zaoxiao; Nyamsi, Serge N.

2018-04-01

Mg-based metal hydride is one of the most promising materials for hydrogen energy storage. However, the high thermal stability due to strong bonding effects between the atoms limits its practical application. In order to reduce the thermal stability, a method of doping double nonmetals into Mg-based system was proposed in this study. The density functional theory (DFT) calculation results showed that the thermal stabilities of both the B-N co-doped Mg-based alloy and its hydride are reduced compared with pure Mg-based system. The relative formation enthalpies of the alloy and its hydride are 0.323 and 0.595 eV atom-1, respectively. The values are much higher than those for either singly B- or N-doped Mg-based system. The more significant destabilization by doping double nonmetal elements than single element is mainly attributed to a dual effect in weakening Mg-Ni/NiH4 bonds, caused by criss-cross interactions between B-Ni and N-Mg bonds.

The destabilization of the French electricity supply industry nascent competition in an open environment

International Nuclear Information System (INIS)

Finon, D.

2001-06-01

In February 2000 France, compelled by the 1996 European Directive 96/92, undertook a minimal reform of the organisation of its electricity industry, while preserving the boundaries of the incumbent company. The aim of this paper is to analyse the conditions of destabilization of the industrial organisation of the French ESI, by identifying the economic factors of endogenous and exogenous erosion. Firstly, after setting out the main elements of the French reform, which is aimed at making the electricity market contestable, the effectiveness of the ''contestability'' of the French power market is discussed. Secondly in order to test the stability of the new institutional arrangements, an institutional prospect is developed, on the basis of economic factors of instability and resistance, to produce two contrasting scenarios: one in which the particularly French model is retained (limited contestability market scenario); another in which there is movement towards a de-integrated competitive model (contamination by competition scenario). Thirdly the author concludes on the basis of recent elements, that the future would be a mix of these two trajectories which will come within in the progressive integration of the national markets in continental Europe. (A.L.B.)

The destabilization of the French electricity supply industry nascent competition in an open environment

Energy Technology Data Exchange (ETDEWEB)

Finon, D

2001-06-01

In February 2000 France, compelled by the 1996 European Directive 96/92, undertook a minimal reform of the organisation of its electricity industry, while preserving the boundaries of the incumbent company. The aim of this paper is to analyse the conditions of destabilization of the industrial organisation of the French ESI, by identifying the economic factors of endogenous and exogenous erosion. Firstly, after setting out the main elements of the French reform, which is aimed at making the electricity market contestable, the effectiveness of the ''contestability'' of the French power market is discussed. Secondly in order to test the stability of the new institutional arrangements, an institutional prospect is developed, on the basis of economic factors of instability and resistance, to produce two contrasting scenarios: one in which the particularly French model is retained (limited contestability market scenario); another in which there is movement towards a de-integrated competitive model (contamination by competition scenario). Thirdly the author concludes on the basis of recent elements, that the future would be a mix of these two trajectories which will come within in the progressive integration of the national markets in continental Europe. (A.L.B.)

BI-2 destabilizes HIV-1 cores during infection and Prevents Binding of CPSF6 to the HIV-1 Capsid.

Science.gov (United States)

Fricke, Thomas; Buffone, Cindy; Opp, Silvana; Valle-Casuso, Jose; Diaz-Griffero, Felipe

2014-12-11

The recently discovered small-molecule BI-2 potently blocks HIV-1 infection. BI-2 binds to the N-terminal domain of HIV-1 capsid. BI-2 utilizes the same capsid pocket used by the small molecule PF74. Although both drugs bind to the same pocket, it has been proposed that BI-2 uses a different mechanism to block HIV-1 infection when compared to PF74. This work demonstrates that BI-2 destabilizes the HIV-1 core during infection, and prevents the binding of the cellular factor CPSF6 to the HIV-1 core. Overall this short-form paper suggests that BI-2 is using a similar mechanism to the one used by PF74 to block HIV-1 infection.

Transcriptome sequencing and positive selected genes analysis of Bombyx mandarina.

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Tingcai Cheng

Full Text Available The wild silkworm Bombyx mandarina is widely believed to be an ancestor of the domesticated silkworm, Bombyx mori. Silkworms are often used as a model for studying the mechanism of species domestication. Here, we performed transcriptome sequencing of the wild silkworm using an Illumina HiSeq2000 platform. We produced 100,004,078 high-quality reads and assembled them into 50,773 contigs with an N50 length of 1764 bp and a mean length of 941.62 bp. A total of 33,759 unigenes were identified, with 12,805 annotated in the Nr database, 8273 in the Pfam database, and 9093 in the Swiss-Prot database. Expression profile analysis found significant differential expression of 1308 unigenes between the middle silk gland (MSG and posterior silk gland (PSG. Three sericin genes (sericin 1, sericin 2, and sericin 3 were expressed specifically in the MSG and three fibroin genes (fibroin-H, fibroin-L, and fibroin/P25 were expressed specifically in the PSG. In addition, 32,297 Single-nucleotide polymorphisms (SNPs and 361 insertion-deletions (INDELs were detected. Comparison with the domesticated silkworm p50/Dazao identified 5,295 orthologous genes, among which 400 might have experienced or to be experiencing positive selection by Ka/Ks analysis. These data and analyses presented here provide insights into silkworm domestication and an invaluable resource for wild silkworm genomics research.

A Novel Variant with Positive Natural Selection Influenced Hb A2 Levels in Chinese Individuals with β-Thalassemia.

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Yu, Shanjuan; Chen, Yang; Lai, Ketong; Dewan, Roma Kajal; He, Yunyan

2017-05-01

β-Thalassemia (β-thal) is the most common inherited hemolytic anemia worldwide. Elevated Hb A 2 is a mark of β-thal carriers. The aim of this study was to identify the pathogenic variants associated with the Hb A 2 levels. One thousand and thirty β-thal carriers were recruited for this study. Using positive natural expression quantitative trait loci (eQTL) analysis, a significant variant was selected. Genotyping for the rs231841 polymorphism was performed by the Sequenom MassARRAY IPLEX platform. All genetic association analyses were performed with the PLINK program. The linear regression analysis showed that rs231841 in the intron region of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene on chromosome 11p15 was significantly associated with Hb A 2 levels. The presence of the C allele was associated with elevated Hb A 2 levels. Our results suggest that rs231841 on the KCNQ1 gene with positive natural selection is related to Hb A 2 levels in Chinese β-thal carriers, and KCNQ1 is probably associated with the expression of the β-like globin gene cluster.

Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins identified by high-throughput screening.

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Weihua Liu

Full Text Available Overexpressed Human epidermal growth factor receptor 2 (HER2 drives the biology of 20% breast cancer and is a prediction of a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients. Traditional Chinese herbs/medicines have been used to treat breast cancer patients including HER2-positive patients in Asia for decades. Although the traditional medicines demonstrate efficacy in clinics for HER2-positive patients, the mechanism is largely unknown. In this article, we screened a 10,000 natural product library in 6 different cell lines representing breast cancer, and assessed the ability of each drug to cause cytotoxicity through a high-throughput screening approach. We have identified eight natural compounds that selectively inhibit the proliferation of HER2-positive cells. Two of the hit compounds, peonidin-3-glucoside and cyaniding-3-glucoside, are both extracts from black rice. They inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3-glucoside and cyaniding-3-glucoside treatments significantly reduced the tumor size and volume in vivo compared to the control group. There is no significant difference of antitumorgenic effects between peonidin-3-glucoside and cyaniding-3-glucoside treatments.

Selectively catalytic activity of metal–organic frameworks depending on the N-position within the pyridine ring of their building blocks

Energy Technology Data Exchange (ETDEWEB)

Xu, Haitao, E-mail: xuhaitao@ecust.edu.cn [School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237 (China); Gou, Yongxia; Ye, Jing; Xu, Zhen-liang [School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237 (China); Wang, Zixuan [School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237 (China)

2016-05-15

Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. 1Fe exhibits a two-dimensional extended-grid network, whereas 2Fe exhibits a stair-like double-chain; the N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Furthermore, selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF; micro/nanoparticles of the layered MOF were therefore investigated for new potential applications of micro/nano MOFs. - Graphical abstract: Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. The N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF. - Highlights: • Synthesis and structure of metal–organic framework [Fe(L){sub 2}(SCN){sub 2}]{sub ∝}. • Selectively catalytic activity depending on the N-position within the pyridine ring. • The degradation and conversion of methyl orange.

Selectively catalytic activity of metal–organic frameworks depending on the N-position within the pyridine ring of their building blocks

International Nuclear Information System (INIS)

Xu, Haitao; Gou, Yongxia; Ye, Jing; Xu, Zhen-liang; Wang, Zixuan

2016-01-01

Iron metal–organic frameworks (MOFs) [Fe(L) 2 (SCN) 2 ] ∝ (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H 2 O solvent system. 1Fe exhibits a two-dimensional extended-grid network, whereas 2Fe exhibits a stair-like double-chain; the N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Furthermore, selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF; micro/nanoparticles of the layered MOF were therefore investigated for new potential applications of micro/nano MOFs. - Graphical abstract: Iron metal–organic frameworks (MOFs) [Fe(L) 2 (SCN) 2 ] ∝ (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H 2 O solvent system. The N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF. - Highlights: • Synthesis and structure of metal–organic framework [Fe(L) 2 (SCN) 2 ] ∝ . • Selectively catalytic activity depending on the N-position within the pyridine ring. • The degradation and conversion of methyl orange.

Positive Selection on Loci Associated with Drug and Alcohol Dependence.

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Brooke Sadler

Full Text Available Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.

Position of the Mental Foramen in Panoramic Radiography and Its Relationship to Age in a Selected Iranian Population

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Dehghani

2016-02-01

Full Text Available Background The position of the mental foramen is critical for surgery and local anesthesia. Objectives This study was conducted to assess the position of the mental foramen and its relationship to age in a selected Iranian population. Materials and Methods This was a cross-sectional descriptive study. Three hundred panoramic radiographs were assessed. Three variables were assessed for each radiograph: anterior-posterior position, superior-inferior position, and radiographic appearance. The position and appearance of the mental foramen were recorded according to gender and age. The results were analyzed using Chi-square and Fisher’s exact tests. Results Considering the anterior-posterior position, the mental foramina were located in the following positions: between premolars (41.5%, at the apex of the second premolars (31.7%, in the posterior area of the second premolars (19.2%, in the anterior area of the first premolars (4.3%, and at the apex of the first premolars (3.3%.The superior-inferior position of the mental foramina were below, above, and at the level of the apices of the premolars in 78.8%, 2.5%, and 18.7% of cases, respectively. The appearance of the mental foramen was continuous in relation to the mandibular canal in 55.9% of cases, while it was separated, diffuse, and unidentified in 29.5%, 9.7%, and 5% of cases, respectively. Age was found to affect the position and appearance of mental foramen. Conclusions The mental foramina were most commonly located between the first and second premolars and below the apex. A continuous appearance was the most common appearance for the mental foramen, which was similar in males and females.

Antibacterial properties of biosurfactants against selected Gram-positive and -negative bacteria.

Science.gov (United States)

Díaz De Rienzo, Mayri A; Stevenson, Paul; Marchant, Roger; Banat, Ibrahim M

2016-01-01

The antibacterial properties and ability to disrupt biofilms of biosurfactants (rhamnolipids, sophorolipids) and sodium dodecyl sulphate (SDS) in the presence and absence of selected organic acids were investigated. Pseudomonas aeruginosa PAO1 was inhibited by sophorolipids and SDS at concentrations >5% v/v, and the growth of Escherichia coli NCTC 10418 was also inhibited by sophorolipids and SDS at concentrations >5% and 0.1% v/v, respectively. Bacillus subtilis NCTC 10400 was inhibited by rhamnolipids, sophorolipids and SDS at concentrations >0.5% v/v of all three; the same effect was observed with Staphylococcus aureus ATCC 9144. The ability to attach to surfaces and biofilm formation of P. aeruginosa PAO1, E. coli NCTC 10418 and B. subtilis NCTC 10400 was inhibited by sophorolipids (1% v/v) in the presence of caprylic acid (0.8% v/v). In the case of S. aureus ATCC 9144, the best results were obtained using caprylic acid on its own. It was concluded that sophorolipids are promising compounds for the inhibition/disruption of biofilms formed by Gram-positive and Gram-negative microorganisms and this activity can be enhanced by the presence of booster compounds such as caprylic acid. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Microtubule Destabilizer KIF2A Undergoes Distinct Site-Specific Phosphorylation Cascades that Differentially Affect Neuronal Morphogenesis

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Tadayuki Ogawa

2015-09-01

Full Text Available Neurons exhibit dynamic structural changes in response to extracellular stimuli. Microtubules (MTs provide rapid and dramatic cytoskeletal changes within the structural framework. However, the molecular mechanisms and signaling networks underlying MT dynamics remain unknown. Here, we have applied a comprehensive and quantitative phospho-analysis of the MT destabilizer KIF2A to elucidate the regulatory mechanisms of MT dynamics within neurons in response to extracellular signals. Interestingly, we identified two different sets of KIF2A phosphorylation profiles that accelerate (A-type and brake (B-type the MT depolymerization activity of KIF2A. Brain-derived neurotrophic factor (BDNF stimulates PAK1 and CDK5 kinases, which decrease the MT depolymerizing activity of KIF2A through B-type phosphorylation, resulting in enhanced outgrowth of neural processes. In contrast, lysophosphatidic acid (LPA induces ROCK2 kinase, which suppresses neurite outgrowth from round cells via A-type phosphorylation. We propose that these two mutually exclusive forms of KIF2A phosphorylation differentially regulate neuronal morphogenesis during development.

SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2

Science.gov (United States)

Naudin, Cécile; Sirvent, Audrey; Leroy, Cédric; Larive, Romain; Simon, Valérie; Pannequin, Julie; Bourgaux, Jean-François; Pierre, Josiane; Robert, Bruno; Hollande, Frédéric; Roche, Serge

2014-01-01

The adaptor SLAP is a negative regulator of receptor signalling in immune cells but its role in human cancer is ill defined. Here we report that SLAP is abundantly expressed in healthy epithelial intestine but strongly downregulated in 50% of colorectal cancer. SLAP overexpression suppresses cell tumorigenicity and invasiveness while SLAP silencing enhances these transforming properties. Mechanistically, SLAP controls SRC/EPHA2/AKT signalling via destabilization of the SRC substrate and receptor tyrosine kinase EPHA2. This activity is independent from CBL but requires SLAP SH3 interaction with the ubiquitination factor UBE4A and SLAP SH2 interaction with pTyr594-EPHA2. SRC phosphorylates EPHA2 on Tyr594, thus creating a feedback loop that promotes EPHA2 destruction and thereby self-regulates its transforming potential. SLAP silencing enhances SRC oncogenicity and sensitizes colorectal tumour cells to SRC inhibitors. Collectively, these data establish a tumour-suppressive role for SLAP in colorectal cancer and a mechanism of SRC oncogenic induction through stabilization of its cognate substrates.

Wnt signaling positively regulates endothelial cell fate specification in the Fli1a-positive progenitor population via Lef1.

Science.gov (United States)

Hübner, Kathleen; Grassme, Kathrin S; Rao, Jyoti; Wenke, Nina K; Zimmer, Cordula L; Korte, Laura; Mu Ller, Katja; Sumanas, Saulius; Greber, Boris; Herzog, Wiebke

2017-10-01

During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2 BAC :Venus-Pest) mu288 ; Tg(14TCF:loxP-STOP-loxP-dGFP) mu202 ). We therefore can detect β-catenin dependent Wnt signaling activity in a subset of the Fli1a-positive progenitor population. Additionally, we show that mesodermal Wnt3a-mediated signaling via the transcription factor Lef1 positively regulates EC specification (defined by kdrl expression) at the expense of primitive erythrocyte specification (defined by gata1 expression) in zebrafish embryos. Using mesoderm derived from human embryonic stem cells, we identified the same principle of Wnt signaling dependent EC specification in conjunction with auto-upregulation of LEF1. Our data indicate a novel role of β-catenin dependent Wnt signaling in regulating EC specification during vasculogenesis. Copyright © 2017. Published by Elsevier Inc.

Destabilization of low mode number Alfven modes in a tokamak by energetic or alpha particles

International Nuclear Information System (INIS)

Tsang, K.T.; Sigmar, D.J.; Whitson, J.C.

1980-12-01

With the inclusion of finite Larmor radius effects in the shear Alfven eigenmode equation, the continuous Alfven spectrum, which has been extensively discussed in ideal magnetohydrodynamics, is removed. Neutrally stable, discrete radial eigenmodes appear in the absence of sources of free energy and dissipation. Alpha (or energetic) particle toroidal drifts destabilize these modes, provided the particles are faster than the Alfven speed. Although the electron Landu resonance contributes to damping, a stability study of the parametric variation of the energy and the density scale length of the energetic particles shows that modes with low radial mode numbers remain unstable in most cases. Since the alpha particles are concentrated in the center of the plasma, this drift-type instability suggests anomalous helium ash diffusion. Indeed, it is shown that stochasticity of alpha orbits due to the overlapping of radially neighboring Alfven resonances is induced at low amplitudes, e/sub i//sup approx./phi/T/sub i/ greater than or equal to 0.05, implying a diffusion coefficient D/sub r//sup α/ greater than or equal to 4.4 x 10 3 cm 2 /s

Destabilizing effect of time-dependent oblique magnetic field on magnetic fluids streaming in porous media.

Science.gov (United States)

El-Dib, Yusry O; Ghaly, Ahmed Y

2004-01-01

The present work studies Kelvin-Helmholtz waves propagating between two magnetic fluids. The system is composed of two semi-infinite magnetic fluids streaming throughout porous media. The system is influenced by an oblique magnetic field. The solution of the linearized equations of motion under the boundary conditions leads to deriving the Mathieu equation governing the interfacial displacement and having complex coefficients. The stability criteria are discussed theoretically and numerically, from which stability diagrams are obtained. Regions of stability and instability are identified for the magnetic fields versus the wavenumber. It is found that the increase of the fluid density ratio, the fluid velocity ratio, the upper viscosity, and the lower porous permeability play a stabilizing role in the stability behavior in the presence of an oscillating vertical magnetic field or in the presence of an oscillating tangential magnetic field. The increase of the fluid viscosity plays a stabilizing role and can be used to retard the destabilizing influence for the vertical magnetic field. Dual roles are observed for the fluid velocity in the stability criteria. It is found that the field frequency plays against the constant part for the magnetic field.

Alpha-conotoxin analogs with additional positive charge show increased selectivity towards Torpedo californica and some neuronal subtypes of nicotinic acetylcholine receptors

NARCIS (Netherlands)

Kasheverov, I.E.; Zhmak, M.N.; Vulfius, C.A.; Corbacheva, E.V.; Mordvintsev, D.Y.; Utkin, Y.N.; van Elk, R.; Smit, A.B.; Tsetlin, V.I.

2006-01-01

α-Conotoxins from Conus snails are indispensable tools for distinguishing various subtypes of nicotinic acetylcholine receptors (nAChRs), and synthesis of α-conotoxin analogs may yield novel antagonists of higher potency and selectivity. We incorporated additional positive charges into α-conotoxins

Take a look at the bright side: Effects of positive body exposure on selective visual attention in women with high body dissatisfaction.

Science.gov (United States)

Glashouwer, Klaske A; Jonker, Nienke C; Thomassen, Karen; de Jong, Peter J

2016-08-01

Women with high body dissatisfaction look less at their 'beautiful' body parts than their 'ugly' body parts. This study tested the robustness of this selective viewing pattern and examined the influence of positive body exposure on body-dissatisfied women's attention for 'ugly' and 'beautiful' body parts. In women with high body dissatisfaction (N = 28) and women with low body dissatisfaction (N = 14) eye-tracking was used to assess visual attention towards pictures of their own and other women's bodies. Participants with high body dissatisfaction were randomly assigned to 5 weeks positive body exposure (n = 15) or a no-treatment condition (n = 13). Attention bias was assessed again after 5 weeks. Body-dissatisfied women looked longer at 'ugly' than 'beautiful' body parts of themselves and others, while participants with low body dissatisfaction attended equally long to own/others' 'beautiful' and 'ugly' body parts. Although positive body exposure was very effective in improving participants' body satisfaction, it did not systematically change participants' viewing pattern. The tendency to preferentially allocate attention towards one's 'ugly' body parts seems a robust phenomenon in women with body dissatisfaction. Yet, modifying this selective viewing pattern seems not a prerequisite for successfully improving body satisfaction via positive body exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exceptional recurrence of flank destabilizations in the recent activity of the Colima volcanic complex, Mexico; Recurrence exceptionnelle de destabilisations de flanc dans l`activite recente du complexe volcanique du Colima, Mexique

Energy Technology Data Exchange (ETDEWEB)

Komorowski, J C [IPGP, (Mexico); Siebe, C [Institut de Geofisica, UNAM (Mexico); Rodriguez, S [Institut de Geologia, UNAM (Mexico); Cortes, A; Navarro, C; Gavilanes, J C

1997-12-31

This short paper reports on new {sup 14}C datings of debris flow units from the Nevado de Colima and Fuego de Colima volcanoes in Mexico. These new datings in connection with a detailed stratigraphic study in the deep canyons around the volcanoes has revealed an exceptional recurrence of flank destabilizations of the Fuego de Colima during the last 45000 years. The cumulated volume of debris in the whole Colima massif is estimated to 60-100 km{sup 3}. The correlation between Landsat satellite pictures and the distribution and age of the debris flows shows that both volcanoes are made of several post-destabilization remaining structures, and that both volcanoes were active and simultaneously collapsed 18500 years ago. The numerous fluvial-lacustrine sequences intercalated between the successive flows indicate that the debris flow were partially sedimented under water and could have led to catastrophic tsunamis towards the Pacific coast. Implications of this work are important because a population of more than 200000 inhabitants is living in a zone covered by several debris flows. (J.S.).

Exceptional recurrence of flank destabilizations in the recent activity of the Colima volcanic complex, Mexico; Recurrence exceptionnelle de destabilisations de flanc dans l`activite recente du complexe volcanique du Colima, Mexique

Energy Technology Data Exchange (ETDEWEB)

Komorowski, J.C. [IPGP, (Mexico); Siebe, C. [Institut de Geofisica, UNAM (Mexico); Rodriguez, S. [Institut de Geologia, UNAM (Mexico); Cortes, A.; Navarro, C.; Gavilanes, J.C.

1996-12-31

This short paper reports on new {sup 14}C datings of debris flow units from the Nevado de Colima and Fuego de Colima volcanoes in Mexico. These new datings in connection with a detailed stratigraphic study in the deep canyons around the volcanoes has revealed an exceptional recurrence of flank destabilizations of the Fuego de Colima during the last 45000 years. The cumulated volume of debris in the whole Colima massif is estimated to 60-100 km{sup 3}. The correlation between Landsat satellite pictures and the distribution and age of the debris flows shows that both volcanoes are made of several post-destabilization remaining structures, and that both volcanoes were active and simultaneously collapsed 18500 years ago. The numerous fluvial-lacustrine sequences intercalated between the successive flows indicate that the debris flow were partially sedimented under water and could have led to catastrophic tsunamis towards the Pacific coast. Implications of this work are important because a population of more than 200000 inhabitants is living in a zone covered by several debris flows. (J.S.).

Trapped fast particle destabilization of internal kink mode for the locally flattened q-profile with an inflection point

Energy Technology Data Exchange (ETDEWEB)

Wang, Xian-Qu [Institute of Fusion Science, School of Physical Science and Technology, Southwest Jiaotong University, Chengdu, Sichuan 610031 (China); Zhang, Rui-Bin; Meng, Guo [State Key Lab of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China)

2016-07-15

The destabilization of ideal internal kink modes by trapped fast particles in tokamak plasmas with a “shoulder”-like equilibrium current is investigated. It is found that energetic particle branch of the mode is unstable with the driving of fast-particle precession drifts and corresponds to a precessional fishbone. The mode with a low stability threshold is also more easily excited than the conventional precessional fishbone. This is different from earlier studies for the same equilibrium in which the magnetohydrodynamic (MHD) branch of the mode is stable. Furthermore, the stability and characteristic frequency of the mode are analyzed by solving the dispersion relation and comparing with the conventional fishbone. The results suggest that an equilibrium with a locally flattened q-profile, may be modified by localized current drive (or bootstrap current, etc.), is prone to the onset of the precessional fishbone branch of the mode.

Phylodynamic analysis of clinical and environmental Vibrio cholerae isolates from Haiti reveals diversification driven by positive selection.

Science.gov (United States)

Azarian, Taj; Ali, Afsar; Johnson, Judith A; Mohr, David; Prosperi, Mattia; Veras, Nazle M; Jubair, Mohammed; Strickland, Samantha L; Rashid, Mohammad H; Alam, Meer T; Weppelmann, Thomas A; Katz, Lee S; Tarr, Cheryl L; Colwell, Rita R; Morris, J Glenn; Salemi, Marco

2014-12-23

Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy. Cholera, a dehydrating diarrheal disease caused by toxigenic strains of the bacterium Vibrio cholerae, emerged in 2010 in Haiti, a country where there were no available records on cholera over the past 100 years. While devastating in terms of morbidity and mortality, the outbreak provided a unique opportunity to study the evolutionary dynamics of V. cholerae and its environmental presence. The present study expands on previous work and provides an in-depth phylodynamic analysis inferred from genome-wide single nucleotide polymorphisms of clinical and environmental strains from dispersed geographic settings in

The developmental outcomes of P0-mediated ARGONAUTE destabilization in tomato.

Science.gov (United States)

Hendelman, Anat; Kravchik, Michael; Stav, Ran; Zik, Moriyah; Lugassi, Nitsan; Arazi, Tzahi

2013-01-01

The plant protein ARGONAUTE1 (AGO1) functions in multiple RNA-silencing pathways, including those of microRNAs, key regulators of growth and development. Genetic analysis of ago1 mutants with informative defects has provided valuable insights into AGO1's biological functions. Tomato encodes two AGO1 homologs (SlAGO1s), but mutants have not been described to date. To analyze SlAGO1s' involvement in development, we confirmed that both undergo decay in the presence of the Polerovirus silencing suppressor P0 and produce a transgenic responder line (OP:P0HA) that, upon transactivation, expresses P0 C-terminally fused to a hemagglutinin (HA) tag (P0HA) and destabilizes SlAGO1s at the site of expression. By crossing OP:P0HA with a battery of driver lines, constitutive as well as organ- and stage-specific SlAGO1 downregulation was induced in the F1 progeny. Activated plants exhibited various developmental phenotypes that partially overlapped with those of Arabidopsis ago1 mutants. Plants that constitutively expressed P0HA had reduced SlAGO1 levels and increased accumulation of miRNA targets, indicating compromised SlAGO1-mediated silencing. Consistent with this, they exhibited pleiotropic morphological defects and their growth was arrested post-germination. Transactivation of P0HA in young leaf and floral organ primordia dramatically modified corresponding organ morphology, including the radialization of leaflets, petals and anthers, suggesting that SlAGO1s' activities are required for normal lateral organ development and polarity. Overall, our results suggest that the OP:P0HA responder line can serve as a valuable tool to suppress SlAGO1 silencing pathways in tomato. The suppression of additional SlAGOs by P0HA and its contribution to the observed phenotypes awaits investigation.

Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases.

Directory of Open Access Journals (Sweden)

Tudor I Oprea

Full Text Available Rho family GTPases (including Rac, Rho and Cdc42 collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID as a structural series. Cheminformatics-based substructure analyses-using the rotationally constrained carboxylate in R-naproxen-led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766 and Cdc42 (CID2950007/ML141 specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid

Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

Directory of Open Access Journals (Sweden)

Richard C Wang

Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

Functional divergence caused by ancient positive selection of a Drosophila hybrid incompatibility locus.

Directory of Open Access Journals (Sweden)

Daniel A Barbash

2004-06-01

Full Text Available Interspecific hybrid lethality and sterility are a consequence of divergent evolution between species and serve to maintain the discrete identities of species. The evolution of hybrid incompatibilities has been described in widely accepted models by Dobzhansky and Muller where lineage-specific functional divergence is the essential characteristic of hybrid incompatibility genes. Experimentally tractable models are required to identify and test candidate hybrid incompatibility genes. Several Drosophila melanogaster genes involved in hybrid incompatibility have been identified but none has yet been shown to have functionally diverged in accordance with the Dobzhansky-Muller model. By introducing transgenic copies of the X-linked Hybrid male rescue (Hmr gene into D. melanogaster from its sibling species D. simulans and D. mauritiana, we demonstrate that Hmr has functionally diverged to cause F1 hybrid incompatibility between these species. Consistent with the Dobzhansky-Muller model, we find that Hmr has diverged extensively in the D. melanogaster lineage, but we also find extensive divergence in the sibling-species lineage. Together, these findings implicate over 13% of the amino acids encoded by Hmr as candidates for causing hybrid incompatibility. The exceptional level of divergence at Hmr cannot be explained by neutral processes because we use phylogenetic methods and population genetic analyses to show that the elevated amino-acid divergence in both lineages is due to positive selection in the distant past-at least one million generations ago. Our findings suggest that multiple substitutions driven by natural selection may be a general phenomenon required to generate hybrid incompatibility alleles.

The NASA competitive placement plan for positions GS-15 and below (including trades and labor positions)

Science.gov (United States)

1993-01-01

This plan provides the framework for selection based on merit from among the best qualified candidates available. Selections will be made without regard to political, religious, or labor organization affiliation or nonaffiliation, marital status, race, color, sex, national origin, nondisqualifying disability, or age. This plan does not guarantee promotion but rather ensures that all qualified available candidates receive fair and equitable consideration for positions filled under these competitive procedures. Announcing a vacancy under this plan is only one method of locating applicants for a position and can be used in conjunction with other methods. Subject to applicable law and regulation, selection of an individual to fill a position is the decision of management, as is the decision as to the method(s) to be used in identifying candidates. This plan is applicable to all NASA Installations. It covers all positions in the competitive service at (and below) the GS/GM-15 level (including all trades and labor positions), except positions in the Office of the Inspector General. The requirements herein are not intended to, nor should they be construed to limit in any way, the independent personnel authority of the Inspector General under the Inspector General Act, as Amended.

Augmenting the Genetic Toolbox for Sulfolobus islandicus with a Stringent Positive Selectable Marker for Agmatine Prototrophy

Science.gov (United States)

Cooper, Tara E.; Krause, David J.

2013-01-01

Sulfolobus species have become the model organisms for studying the unique biology of the crenarchaeal division of the archaeal domain. In particular, Sulfolobus islandicus provides a powerful opportunity to explore natural variation via experimental functional genomics. To support these efforts, we further expanded genetic tools for S. islandicus by developing a stringent positive selection for agmatine prototrophs in strains in which the argD gene, encoding arginine decarboxylase, has been deleted. Strains with deletions in argD were shown to be auxotrophic for agmatine even in nutrient-rich medium, but growth could be restored by either supplementation of exogenous agmatine or reintroduction of a functional copy of the argD gene from S. solfataricus P2 into the ΔargD host. Using this stringent selection, a robust targeted gene knockout system was established via an improved next generation of the MID (marker insertion and unmarked target gene deletion) method. Application of this novel system was validated by targeted knockout of the upsEF genes involved in UV-inducible cell aggregation formation. PMID:23835176

Detecting selection needs comparative data

DEFF Research Database (Denmark)

Nielsen, Rasmus; Hubisz, Melissa J.

2005-01-01

Positive selection at the molecular level is usually indicated by an increase in the ratio of non-synonymous to synonymous substitutions (dN/dS) in comparative data. However, Plotkin et al. 1 describe a new method for detecting positive selection based on a single nucleotide sequence. We show here...... that this method is particularly sensitive to assumptions regarding the underlying mutational processes and does not provide a reliable way to identify positive selection....

Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.

Science.gov (United States)

Coutinho, A; Caramalho, I; Seixas, E; Demengeot, J

2005-01-01

The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al. 1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that peripheral tissue-specific tolerance is centrally established in the thymus, by epithelial stromal cells (TEC). Subsequent experiments have shown that TEC-tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are generated intrathymically by recognition of antigens expressed on TECs (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other observations, in 1996 Modigliani and colleagues derived a general model for the establishment and maintenance of natural tolerance (MM96) (Modigliani et al. 1996b), with two central propositions: (1) T cell receptor (TCR)-dependent sorting of emergent repertoires generates TEC-specific Treg displaying the highest TCR self-affinities below deletion thresholds, thus isolating repertoires undergoing positive and negative selection; (2) Treg are intrathymically committed (and activated) for a unique differentiative pathway with regulatory effector functions. The model explained the embryonic/perinatal time window of natural tolerance acquisition, by developmental programs determining (1) TCR multireactivity, (2) the cellular composition in the thymic stroma (relative abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that remain recruitable to regulatory functions. We discuss here the MM96 in the light of recent results demonstrating the promiscuous expression of tissue-specific antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004) and indicating that Treg represent a unique differentiative pathway (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan et al. 2001; Apostolou et al. 2002). In the likelihood that

Positive mood broadens visual attention to positive stimuli.

Science.gov (United States)

Wadlinger, Heather A; Isaacowitz, Derek M

2006-03-01

In an attempt to investigate the impact of positive emotions on visual attention within the context of Fredrickson's (1998) broaden-and-build model, eye tracking was used in two studies to measure visual attentional preferences of college students (n=58, n=26) to emotional pictures. Half of each sample experienced induced positive mood immediately before viewing slides of three similarly-valenced images, in varying central-peripheral arrays. Attentional breadth was determined by measuring the percentage viewing time to peripheral images as well as by the number of visual saccades participants made per slide. Consistent with Fredrickson's theory, the first study showed that individuals induced into positive mood fixated more on peripheral stimuli than did control participants; however, this only held true for highly-valenced positive stimuli. Participants under induced positive mood also made more frequent saccades for slides of neutral and positive valence. A second study showed that these effects were not simply due to differences in emotional arousal between stimuli. Selective attentional broadening to positive stimuli may act both to facilitate later building of resources as well as to maintain current positive affective states.

Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.

Science.gov (United States)

Pace, Vittorio; Holzer, Wolfgang; Meng, Guangrong; Shi, Shicheng; Lalancette, Roger; Szostak, Roman; Szostak, Michal

2016-10-04

Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HIV-positive patients’ perceptions of care received at a selected antiretroviral therapy clinic in Vhembe district, South Africa

Directory of Open Access Journals (Sweden)

Tshifhiwa V. Ndou

2016-04-01

Full Text Available Background: Patients’ experiences are a reflection of what has happened during the care process and, therefore, provide information about the performance of health care professional workers. They refer to the process of care provision at the antiretroviral therapy (ART sites. Aim and setting: This article explored the perceptions of HIV-positive patients of care received at the Gateway Clinic of the regional hospital that provides antiretroviral treatment in the Vhembe district. Methods: A qualitative, explorative and descriptive design was used. A non-probability, convenient sampling method was used to select 20 HIV-positive patients who were above 18 years of age. In-depth individual interviews were used to collect data. Data were analysed through Tech’s open coding method. Results: One theme and two sub-themes emerged, namely positive experiences related to the environment and attitudes of health professionals, and negative experiences concerning the practices by health care providers. Conclusion: Patients’ perceptions of quality of, and satisfaction with, health care may affect health outcomes. Recommendations are made to consider, practice and strengthen the protocols, the standard operating procedures and the principles of infection control in the health facilities. Keywords: Human Immunodeficiecy Virus, Antiretroviral Treatment, HIV positive, Limpopo

Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

Science.gov (United States)

Garvin, Michael R; Bielawski, Joseph P; Gharrett, Anthony J

2011-01-01

The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

Science.gov (United States)

Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.

2011-01-01

The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm. PMID:21969854

Positional Differences in Elite Basketball: Selecting Appropriate Training - Load Measures.

Science.gov (United States)

Svilar, Luka; Castellano, Julen; Jukic, Igor; Casamichana, David

2018-01-18

The purpose of this paper was to study the structure of interrelationships among external training load measures and how these vary among different positions in elite basketball. Eight external variables of jumping (JUMP), acceleration (ACC), deceleration (DEC) and change of direction (COD), and two internal load variables (RPE and sRPE) were collected from 13 professional players with 300 session records. Three playing positions were considered: guards (n=4), forwards (n=4) and centers (n=5). High and total external variables (hJUMP and tJUMP, hACC and tACC, hDEC and tDEC, hCOD and tCOD) were used for the principal component analysis. Extraction criteria were set at the eigenvalue of greater than one. Varimax rotation mode was used to extract multiple principal components. The analysis showed that all positions had two or three principal components (explaining almost all of the variance), but the configuration of each factor was different: tACC, tDEC, tCOD and hJUMP for centers, hACC, tACC, tCOD and hJUMP for guards, and tACC, hDEC, tDEC, hCOD, and tCOD for forwards are specifically demanded in training sessions and, therefore, these variables must be prioritized in load monitoring. Furthermore, for all playing positions, RPE and sRPE have high correlation with the total amount of ACC, DEC and COD. This would suggest that, although players perform the same training tasks, the demands of each position can vary. A particular combination of external load measures is required to describe training load of each playing position, especially to better understand internal responses among players.

Selection of the new position for the instrumented fuel Flip type; Seleccion de la nueva posicion para el combustible instrumentado tipo Flip

Energy Technology Data Exchange (ETDEWEB)

Paredes G, L C

1991-12-15

It was selected and proved the new position for the instrumented fuel, in function of the smallest influence on the temperature of the fuel due to movements of the control bars, as well as to its functionality regarding their geometric localization in the core. Therefore, it intends that the instrumented fuel Flip type, pass from the position C-9 to the C-6. It was selected the turn angle of the fuel of 180 C, for to be the one that presents a smaller influence of the control bars and it allows to register the values of temperature but high. It was as the movements of the control bars they produce local interferences of the neutron flow in the fuels and that in the case of the ring C, these interferences became maximum variations of the fuel temperature of 125 C, for operations to 1 MW in the thermal column. (Author)

Lysine-specific demethylase 1 (LSD1) destabilizes p62 and inhibits autophagy in gynecologic malignancies.

Science.gov (United States)

Chao, Angel; Lin, Chiao-Yun; Chao, An-Ning; Tsai, Chia-Lung; Chen, Ming-Yu; Lee, Li-Yu; Chang, Ting-Chang; Wang, Tzu-Hao; Lai, Chyong-Huey; Wang, Hsin-Shih

2017-09-26

Lysine-specific demethylase 1 (LSD1) - also known as KDM1A - is the first identified histone demethylase. LSD1 is highly expressed in numerous human malignancies and has recently emerged as a target for anticancer drugs. Owing to the presence of several functional domains, we speculated that LSD1 could have additional functions other than histone demethylation. P62 - also termed sequestasome 1 (SQSTM1) - plays a key role in malignant transformation, apoptosis, and autophagy. Here, we show that a high LSD1 expression promotes tumorigenesis in gynecologic malignancies. Notably, LSD1 inhibition with either siRNA or pharmacological agents activates autophagy. Mechanistically, LSD1 decreases p62 protein stability in a demethylation-independent manner. Inhibition of LSD1 reduces both tumor growth and p62 protein degradation in vivo . The combination of LSD1 inhibition and p62 knockdown exerts additive anticancer effects. We conclude that LSD1 destabilizes p62 and inhibits autophagy in gynecologic cancers. LSD1 inhibition reduces malignant cell growth and activates autophagy. The combinations of LSD1 inhibition and autophagy blockade display additive inhibitory effect on cancer cell viability. A better understanding of the role played by p62 will shed more light on the anticancer effects of LSD1 inhibitors.

An analysis of Patterns of Change Arising from the Syrian Conflict: Islamic Terrorism, Refugee Flows and Political Destabilization in Europe

Directory of Open Access Journals (Sweden)

Erika Brady

2017-02-01

Full Text Available This paper set out to explore whether the Syrian Conflict has impacted security issues outside its borders, in particular in Europe. With a wide range of challenges related to the conflict, now in its sixth year, issues such as the rise of ISIS and the refugee crisis in Europe have been linked to political destabilization on the continent and within the EU. By looking at data presented by the Global Terrorism Database and the United Nations Commissioner for Human Rights (UNHCR, this study set out to observe any patterns in Islamic terrorist activity and numbers of refugees in Europe during the period 2006 to 2015. Academic reports based on empirical studies as well as media reports were also analyzed to further the research and allow for in-depth assessment of the issue as a whole.

Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

Directory of Open Access Journals (Sweden)

Michael R Garvin

Full Text Available The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium.

Science.gov (United States)

Gribble, Phillip A; Delahunt, Eamonn; Bleakley, Chris; Caulfield, Brian; Docherty, Carrie; Fourchet, François; Fong, Daniel Tik-Pui; Hertel, Jay; Hiller, Claire; Kaminski, Thomas; McKeon, Patrick; Refshauge, Kathryn; van der Wees, Philip; Vincenzino, Bill; Wikstrom, Erik

2014-07-01

While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Constraints on arm selection processes when reaching: degrees of freedom and joint amplitudes interact to influence limb selection.

Science.gov (United States)

Kim, Wondae; Buchanan, John; Gabbard, Carl

2011-01-01

With an interest in identifying the variables that constrain arm choice when reaching, the authors had 11 right-handed participants perform free-choice and assigned-limb reaches at 9 object positions. The right arm was freely selected 100% of the time when reaching to positions at 30° and 40° into right hemispace. However, the left arm was freely selected to reach to positions at -30° and -40° in left hemispace 85% of the time. A comparison between free- and assigned-limb reaching kinematics revealed that free limb selection when reaching to the farthest positions was constrained by joint amplitude requirements and the time devoted to limb deceleration. Differences between free- and assigned-arm reaches were not evident when reaching to the midline and positions of ±10°, even though the right arm was freely selected most often for these positions. Different factors contribute to limb selection as a function of distance into a specific hemispace.

Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection.

Science.gov (United States)

Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A

2016-03-01

A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Socially selected ornaments and fitness: Signals of fighting ability in paper wasps are positively associated with survival, reproductive success, and rank.

Science.gov (United States)

Tibbetts, Elizabeth A; Forrest, Taylor; Vernier, Cassondra; Jinn, Judy; Madagame, Andrew

2015-11-01

Many animals have ornaments that mediate choice and competition in social and sexual contexts. Individuals with elaborate sexual ornaments typically have higher fitness than those with less elaborate ornaments, but less is known about whether socially selected ornaments are associated with fitness. Here, we test the relationship between fitness and facial patterns that are a socially selected signal of fighting ability in Polistes dominula wasps. We found wasps that signal higher fighting ability have larger nests, are more likely to survive harsh winters, and obtain higher dominance rank than wasps that signal lower fighting ability. In comparison, body weight was not associated with fitness. Larger wasps were dominant over smaller wasps, but showed no difference in nest size or survival. Overall, the positive relationship between wasp facial patterns and fitness indicates that receivers can obtain diverse information about a signaler's phenotypic quality by paying attention to socially selected ornaments. Therefore, there are surprisingly strong parallels between the information conveyed by socially and sexually selected signals. Similar fitness relationships in social and sexually selected signals may be one reason it can be difficult to distinguish the role of social versus sexual selection in ornament evolution. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia.

Science.gov (United States)

Liu, Xuanyao; Yunus, Yushimah; Lu, Dongsheng; Aghakhanian, Farhang; Saw, Woei-Yuh; Deng, Lian; Ali, Mohammad; Wang, Xu; Nor, Fadzilah Mohd; Ghazali, Fadzilah; Rahman, Thuhairah Abdul; Shaari, Shahrul Azlin; Salleh, Mohd Zaki; Phipps, Maude E; Ong, Rick Twee-Hee; Xu, Shuhua; Teo, Yik-Ying; Hoh, Boon-Peng

2015-04-01

The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.

Mechanisms of microbial destabilization of soil C shifts over decades of warming

Science.gov (United States)

DeAngelis, K.; Pold, G.; Chowdhury, P. R.; Schnabel, J.; Grandy, S.; Melillo, J. M.

2017-12-01

species. Together, these data suggest that after decades of warming both direct kinetic effects and indirect effects of altered substrate availability are affecting microbial ecology and evolution in ways that conspire to destabilize soil organic matter.

A strategy for position-selective epoxidation of polyprenols.

Science.gov (United States)

Gnanadesikan, Vijay; Corey, E J

2008-06-25

An effective strategy has been developed for the efficient site-selective epoxidation of poylolefinic isoprenoid alcohols, based on the use of an internal control element for intramolecular reaction. The approach is illustrated by application to a series of polyisoprenoid alcohols (polyprenols) at substrate concentration of 0.5 mM. With polyprenol substrates having the hydroxyl function at one terminus, the internal epoxidation can be directed at the double bond of the polyprenol, which is either four or five away from the terminal hydroxyprenyl subunit.

New evidence for positive selection helps explain the paternal age effect observed in achondroplasia

Science.gov (United States)

Shinde, Deepali N.; Elmer, Dominik P.; Calabrese, Peter; Boulanger, Jérôme; Arnheim, Norman; Tiemann-Boege, Irene

2013-01-01

There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age effect (PAE). The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single-nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year-old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false-positive rate lower than 2.7 × 10−6. We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead, we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism. PMID:23740942

The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin.

Science.gov (United States)

Cavaliere, Rosalia; Ball, Jessica L; Turnbull, Lynne; Whitchurch, Cynthia B

2014-08-01

Nontypeable Hemophilus influenzae (NTHi) is a Gram-negative bacterial pathogen that causes chronic biofilm infections of the ears and airways. The biofilm matrix provides structural integrity to the biofilm and protects biofilm cells from antibiotic exposure by reducing penetration of antimicrobial compounds into the biofilm. Extracellular DNA (eDNA) has been found to be a major matrix component of biofilms formed by many species of Gram-positive and Gram-negative bacteria, including NTHi. Interestingly, the cation chelator ethylenediaminetetra-acetic acid (EDTA) has been shown to reduce the matrix strength of biofilms of several bacterial species as well as to have bactericidal activity against various pathogens. EDTA exerts its antimicrobial activity by chelating divalent cations necessary for growth and membrane stability and by destabilizing the matrix thus enhancing the detachment of bacterial cells from the biofilm. In this study, we have explored the role of divalent cations in NTHi biofilm development and stability. We have utilized in vitro static and continuous flow models of biofilm development by NTHi to demonstrate that magnesium cations enhance biofilm formation by NTHi. We found that the divalent cation chelator EDTA is effective at both preventing NTHi biofilm formation and at treating established NTHi biofilms. Furthermore, we found that the matrix destablilizers EDTA and DNaseI increase the susceptibility of NTHi biofilms to ampicillin and ciprofloxacin. Our observations indicate that DNaseI and EDTA enhance the efficacy of antibiotic treatment of NTHi biofilms. These observations may lead to new strategies that will improve the treatment options available to patients with chronic NTHi infections. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Destabilization, Propagation, and Generation of Surfactant-Stabilized Foam during Crude Oil Displacement in Heterogeneous Model Porous Media.

Science.gov (United States)

Xiao, Siyang; Zeng, Yongchao; Vavra, Eric D; He, Peng; Puerto, Maura; Hirasaki, George J; Biswal, Sibani L

2018-01-23

Foam flooding in porous media is of increasing interest due to its numerous applications such as enhanced oil recovery, aquifer remediation, and hydraulic fracturing. However, the mechanisms of oil-foam interactions have yet to be fully understood at the pore level. Here, we present three characteristic zones identified in experiments involving the displacement of crude oil from model porous media via surfactant-stabilized foam, and we describe a series of pore-level dynamics in these zones which were not observed in experiments involving paraffin oil. In the displacement front zone, foam coalesces upon initial contact with crude oil, which is known to destabilize the liquid lamellae of the foam. Directly upstream, a transition zone occurs where surface wettability is altered from oil-wet to water-wet. After this transition takes place, a strong foam bank zone exists where foam is generated within the porous media. We visualized each zone using a microfluidic platform, and we discuss the unique physicochemical phenomena that define each zone. In our analysis, we also provide an updated mechanistic understanding of the "smart rheology" of foam which builds upon simple "phase separation" observations in the literature.

Natural Selection in the Great Apes.

Science.gov (United States)

Cagan, Alexander; Theunert, Christoph; Laayouni, Hafid; Santpere, Gabriel; Pybus, Marc; Casals, Ferran; Prüfer, Kay; Navarro, Arcadi; Marques-Bonet, Tomas; Bertranpetit, Jaume; Andrés, Aida M

2016-12-01

Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Positioning the Intracellular Salt Potassium Glutamate in the Hofmeister Series by Chemical Unfolding Studies of NTL9.

Science.gov (United States)

Sengupta, Rituparna; Pantel, Adrian; Cheng, Xian; Shkel, Irina; Peran, Ivan; Stenzoski, Natalie; Raleigh, Daniel P; Record, M Thomas

2016-04-19

In vitro, replacing KCl with potassium glutamate (KGlu), the Escherichia coli cytoplasmic salt and osmolyte, stabilizes folded proteins and protein-nucleic acid complexes. To understand the chemical basis for these effects and rank Glu- in the Hofmeister anion series for protein unfolding, we quantify and interpret the strong stabilizing effect of KGlu on the ribosomal protein domain NTL9, relative to the effects of other stabilizers (KCl, KF, and K2SO4) and destabilizers (GuHCl and GuHSCN). GuHSCN titrations at 20 ° C, performed as a function of the concentration of KGlu or another salt and monitored by NTL9 fluorescence, are analyzed to obtain R-values quantifying the Hofmeister salt concentration (m3) dependence of the unfolding equilibrium constant K(obs) [r-value = −d ln K(obs)/dm3 = (1/RT) dΔG(obs) ° /dm3 = m-value/RT]. r-Values for both stabilizing K+ salts and destabilizing GuH+ salts are compared with predictions from model compound data. For two-salt mixtures, we find that contributions of stabilizing and destabilizing salts to observed r-values are additive and independent. At 20 ° C, we determine a KGlu r-value of 3.22 m(−1) and K2SO4, KF, KCl, GuHCl, and GuHSCN r-values of 5.38, 1.05, 0.64, −1.38, and −3.00 m(−1), respectively. The KGlu r-value represents a 25-fold (1.9 kcal) stabilization per molal KGlu added. KGlu is much more stabilizing than KF, and the stabilizing effect of KGlu is larger in magnitude than the destabilizing effect of GuHSCN. Interpretation of the data reveals good agreement between predicted and observed relative r-values and indicates the presence of significant residual structure in GuHSCN-unfolded NTL9 at 20 ° C.

Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African Buffalo: a plausible new mechanism for a high frequency anomaly.

Directory of Open Access Journals (Sweden)

Pim van Hooft

Full Text Available Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations, we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has

The roles of gene duplication, gene conversion and positive selection in rodent Esp and Mup pheromone gene families with comparison to the Abp family.

Science.gov (United States)

Karn, Robert C; Laukaitis, Christina M

2012-01-01

Three proteinaceous pheromone families, the androgen-binding proteins (ABPs), the exocrine-gland secreting peptides (ESPs) and the major urinary proteins (MUPs) are encoded by large gene families in the genomes of Mus musculus and Rattus norvegicus. We studied the evolutionary histories of the Mup and Esp genes and compared them with what is known about the Abp genes. Apparently gene conversion has played little if any role in the expansion of the mouse Class A and Class B Mup genes and pseudogenes, and the rat Mups. By contrast, we found evidence of extensive gene conversion in many Esp genes although not in all of them. Our studies of selection identified at least two amino acid sites in β-sheets as having evolved under positive selection in the mouse Class A and Class B MUPs and in rat MUPs. We show that selection may have acted on the ESPs by determining K(a)/K(s) for Exon 3 sequences with and without the converted sequence segment. While it appears that purifying selection acted on the ESP signal peptides, the secreted portions of the ESPs probably have undergone much more rapid evolution. When the inner gene converted fragment sequences were removed, eleven Esp paralogs were present in two or more pairs with K(a)/K(s) >1.0 and thus we propose that positive selection is detectable by this means in at least some mouse Esp paralogs. We compare and contrast the evolutionary histories of all three mouse pheromone gene families in light of their proposed functions in mouse communication.

Genomic selection strategies in breeding programs: Strong positive interaction between application of genotypic information and intensive use of young bulls on genetic gain

DEFF Research Database (Denmark)

Buch, Line Hjortø; Sørensen, Morten Kargo; Berg, Peer

2012-01-01

We tested the following hypotheses: (i) breeding schemes with genomic selection are superior to breeding schemes without genomic selection regarding annual genetic gain of the aggregate genotype (ΔGAG), annual genetic gain of the functional traits and rate of inbreeding per generation (ΔF), (ii......) a positive interaction exists between the use of genotypic information and a short generation interval on ΔGAG and (iii) the inclusion of an indicator trait in the selection index will only result in a negligible increase in ΔGAG if genotypic information about the breeding goal trait is known. We examined......, greater contributions of the functional trait to ΔGAG and lower ΔF than the two breeding schemes without genomic selection. Thus, the use of genotypic information may lead to more sustainable breeding schemes. In addition, a short generation interval increases the effect of using genotypic information...

Positive dielectrophoresis used for selective trapping of nanoparticles from flue gas in a gradient field electrodes device

Energy Technology Data Exchange (ETDEWEB)

Lungu, Mihail, E-mail: lmihai@physics.uvt.ro; Neculae, Adrian; Lungu, Antoanetta [West University of Timisoara, Faculty of Physics (Romania)

2015-12-15

This paper investigates the possibility to use positive dielectrophoresis (pDEP) for selective trapping of nanoparticle dispersed in flue gas in a vertical pDEP-based microfluidic system. The experimental gradient field electrodes device contains as main part a vertical deposition plate with parallel planar electrodes in single connection on an insulating substrate, parallel to the reference electrode—a dielectric plate with a metalized side. The performances of the device were described and analyzed by numerical simulations and experimental tests in terms of two new specific parameters, called Retention rate and Filtration, related to the trapping of nanoparticles in suspension inside the device and the consequent purification of flue gas. It is outlined, both numerically and experimentally, that the concentration of particles trapped inside the device decreases as they are moving away from the inlet zone. The experimental results also highlight the nanoparticle size distribution of the particles collected from the deposition plate, using a nanoparticle tracking analysis method, and their selective capture on the deposition plate, depending on the amplitude and shape of the applied voltage, in a good agreement with the numerical simulations results.

Mechanism of Enzyme Repair by the AAA+ Chaperone Rubisco Activase.

Science.gov (United States)

Bhat, Javaid Y; Miličić, Goran; Thieulin-Pardo, Gabriel; Bracher, Andreas; Maxwell, Andrew; Ciniawsky, Susanne; Mueller-Cajar, Oliver; Engen, John R; Hartl, F Ulrich; Wendler, Petra; Hayer-Hartl, Manajit

2017-09-07

How AAA+ chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA+ protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of process parameters and injector position on the efficiency of NOx reduction by selective non catalytic reduction technique

International Nuclear Information System (INIS)

Hamid, A.; Mehmood, M.A.; Irfan, N.; Javed, M.T.; Waheed, K.

2009-01-01

An experimental investigation has been performed to study the effect of atomizer pressure dilution of the reducing reagent and the injector position on the efficiency or the NOx reduction by a selective non-catalytic reduction technique using urea as a reducing agent. Experiments were performed with a flow reactor in which flue gas was generated by the combustion of methane in air at stoichiometric amount of oxygen and the desired levels of initial NOx (400-450 ppm) were achieved by doping the flame with ammonia. The work was directed to investigate the effect of atomizer pressure, dilution of urea reagent and the injector position. The atomizer pressure was varied from 1 to 3bar and 20-25% increase in efficiency was observed by decreasing the pressure. Effect of dilution of urea solution was investigated by varying the strength of the solution from the 8 to 32% and 40-45% increase in the efficiency was observed. Effects of injector position was investigated by injecting the urea solution both in co current and counter current direction of the flue gases and 20-25% increase in the efficiency was observed in counter current direction. (author)

Device to position selectively a tool carried by a vehicle moving on the perforated plate of a tube bundle

International Nuclear Information System (INIS)

Bernardin, M.

1985-01-01

The aim of the invention is an examination device for a tube bundle of an apparatus such as, but not restrictively, a steam generator, situated in a dangerous zone, e.g. radioactive and designed to be introduced into the water box of the said and placed against the perforated plate of the tube bundle by an operator working outside of the said apparatus and able to operate whatever the vertical or horizontal position of the tube plate. The device has a selectively positionable tool - carrying vehicle comprising pistons positioning fingers extendable into the tubes and mounted on extendable supports perpendicular to the pistons and to each other, and an articulated telescopic arm fixed at one end to a rotary mounting on the vehicle and at the other end to an access opening in the vessel containing the tube plate, to hold the vehicle against the plate [fr

Connection of position sensing circuit of regulating body

International Nuclear Information System (INIS)

Janosek, B.

1988-01-01

The source of position pulses is connected to the evaluation unit to which is also connected a display which in turn is connected to a numerical selection unit connected via a power output to the action drive unit. A feedback member is connected between the evaluation unit and the numerical selection unit. Changes in the position of the regulating body produces voltage in the position sensor proportional to the actual value of this change. Voltage pulses are led via a measuring amplifier to the evaluation unit. After amplification the pulses are compared with the value on the numerical selection unit connected in the feedback branch to the measuring amplifier which evaluates differential values of pulses shown on the display in form of instantaneous and required values. The required value is selected via the numerical unit. (J.B.). 1 fig

Intraocular lens power selection and positioning with and without intraoperative aberrometry.

Science.gov (United States)

Hatch, Kathryn M; Woodcock, Emily C; Talamo, Jonathan H

2015-04-01

To determine the value of intraoperative aberrometry in cases of toric intraocular lens (IOL) implantation and positioning. In this non-randomized retrospective comparative trial, two groups of eyes underwent cataract extraction with toric IOL implantation: the aberrometry group (n = 37 eyes), where toric IOL power and alignment were determined before surgery with automated keratometry, standard optical biometry, and an online calculator and then refined using intraoperative aberrometry, and the toric calculator group (n = 27 eyes), where IOL selection was performed in a similar manner but without intraoperative aberrometry. The primary outcome measure was mean postoperative residual refractive astigmatism (RRA). Mean RRA measured at follow-up after surgery was 0.46 ± 0.42 and 0.68 ± 0.34 diopters (D) in the aberrometry and toric calculator groups, respectively (P = .0153). A 75% and 57% reduction in cylinder was noted between preoperative keratometric astigmatism and postoperative RRA in the aberrometry and toric calculator groups, respectively (P = .0027). RRA of 0.25 D or less, 0.50 D or less, 0.75 D or less, and 1.00 D or less was seen 38%, 78%, 86%, and 95% of the time, respectively, in the aberrometry group and 22%, 33%, 74%, and 89% of the time, respectively, in the toric calculator group. These data show that the chance of a patient being in a lower postoperative RRA range increased when intraoperative aberrometry was used (P = .0130). Patients undergoing cataract extraction with toric IOL placement aided by intraoperative aberrometry were 2.4 times more likely to have less than 0.50 D of RRA compared to standard methods. Copyright 2015, SLACK Incorporated.

Pearl millet transformation system using the positive selectable marker gene phosphomannose isomerase

CSIR Research Space (South Africa)

O'Kennedy, MM

2004-04-01

Full Text Available of the transgene. Similar to results obtained from previous studies with maize and wheat, the manA gene was shown to be a superior selectable marker gene for improving transformation efficiencies when compared to antibiotic or herbicide selectable marker genes....

Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

Science.gov (United States)

Andrews, T Daniel; Gojobori, Takashi

2004-01-01

The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia.

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Metspalu, Mait; Romero, Irene Gallego; Yunusbayev, Bayazit; Chaubey, Gyaneshwer; Mallick, Chandana Basu; Hudjashov, Georgi; Nelis, Mari; Mägi, Reedik; Metspalu, Ene; Remm, Maido; Pitchappan, Ramasamy; Singh, Lalji; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

2011-12-09

South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.

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de Vries, Y A; Roest, A M; Franzen, M; Munafò, M R; Bastiaansen, J A

2016-10-01

Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings. A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined. In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%. Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

Selection of Phototransduction Genes in Homo sapiens.

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Christopher, Mark; Scheetz, Todd E; Mullins, Robert F; Abràmoff, Michael D

2013-08-13

We investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level. SNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively. Six of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes. There is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.

Source apportionment and location by selective wind sampling and Positive Matrix Factorization.

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Venturini, Elisa; Vassura, Ivano; Raffo, Simona; Ferroni, Laura; Bernardi, Elena; Passarini, Fabrizio

2014-10-01

In order to determine the pollution sources in a suburban area and identify the main direction of their origin, PM2.5 was collected with samplers coupled with a wind select sensor and then subjected to Positive Matrix Factorization (PMF) analysis. In each sample, soluble ions, organic carbon, elemental carbon, levoglucosan, metals, and Polycyclic Aromatic Hydrocarbons (PAHs) were determined. PMF results identified six main sources affecting the area: natural gas home appliances, motor vehicles, regional transport, biomass combustion, manufacturing activities, and secondary aerosol. The connection of factor temporal trends with other parameters (i.e., temperature, PM2.5 concentration, and photochemical processes) confirms factor attributions. PMF analysis indicated that the main source of PM2.5 in the area is secondary aerosol. This should be mainly due to regional contributions, owing to both the secondary nature of the source itself and the higher concentration registered in inland air masses. The motor vehicle emission source contribution is also important. This source likely has a prevalent local origin. The most toxic determined components, i.e., PAHs, Cd, Pb, and Ni, are mainly due to vehicular traffic. Even if this is not the main source in the study area, it is the one of greatest concern. The application of PMF analysis to PM2.5 collected with this new sampling technique made it possible to obtain more detailed results on the sources affecting the area compared to a classical PMF analysis.

Positioning and applications

Directory of Open Access Journals (Sweden)

Rogowski Jerzy B.

2015-12-01

Full Text Available The paper presents national report of Poland for IAG on positioning and applications. The selected research presented was carried out at leading Polish research institutions and concern precise multi-GNSS satellite positioning - relative and absolute - and also GNSS-based ionosphere and troposphere modelling and studies. The research resulted in noticeable advancements in these subjects confirmed by the development of new algorithms and methods. New and improved methods of precise GNSS positioning were developed, and also GNSS metrology was studied. New advanced troposphere models were presented and tested. In particular, these models allowed testing IPW variability on regional and global scales. Also, new regional ionosphere monitoring web-based services were developed and launched.

Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

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Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

2014-09-01

Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn∆HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite.

Optimization of Cognitive Radio Secondary Information Gathering Station Positioning and Operating Channel Selection for IoT Sensor Networks

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Jinyi Wen

2018-01-01

Full Text Available The Internet of Things (IoT is the interconnection of different objects through the internet using different communication technologies. The objects are equipped with sensors and communications modules. The cognitive radio network is a key technique for the IoT and can effectively address spectrum-related issues for IoT applications. In our paper, a novel method for IoT sensor networks is proposed to obtain the optimal positions of secondary information gathering stations (SIGSs and to select the optimal operating channel. Our objective is to maximize secondary system capacity while protecting the primary system. In addition, we propose an appearance probability matrix for secondary IoT devices (SIDs to maximize the supportable number of SIDs that can be installed in a car, in wearable devices, or for other monitoring devices, based on optimal deployment and probability. We derive fitness functions based on the above objectives and also consider signal to interference-plus-noise ratio (SINR and position constraints. The particle swarm optimization (PSO technique is used to find the best position and operating channel for the SIGSs. In a simulation study, the performance of the proposed method is evaluated and compared with a random resources allocation algorithm (parts of this paper were presented at the ICTC2017 conference (Wen et al., 2017.

Method of generating ploynucleotides encoding enhanced folding variants

Energy Technology Data Exchange (ETDEWEB)

Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

2017-05-02

The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

Absence of positive selection on CenH3 in Luzula suggests that holokinetic chromosomes may suppress centromere drive.

Science.gov (United States)

Zedek, František; Bureš, Petr

2016-12-01

The centromere drive theory explains diversity of eukaryotic centromeres as a consequence of the recurrent conflict between centromeric repeats and centromeric histone H3 (CenH3), in which selfish centromeres exploit meiotic asymmetry and CenH3 evolves adaptively to counterbalance deleterious consequences of driving centromeres. Accordingly, adaptively evolving CenH3 has so far been observed only in eukaryotes with asymmetric meiosis. However, if such evolution is a consequence of centromere drive, it should depend not only on meiotic asymmetry but also on monocentric or holokinetic chromosomal structure. Selective pressures acting on CenH3 have never been investigated in organisms with holokinetic meiosis despite the fact that holokinetic chromosomes have been hypothesized to suppress centromere drive. Therefore, the present study evaluates selective pressures acting on the CenH3 gene in holokinetic organisms for the first time, specifically in the representatives of the plant genus Luzula (Juncaceae), in which the kinetochore formation is not co-localized with any type of centromeric repeat. PCR, cloning and sequencing, and database searches were used to obtain coding CenH3 sequences from Luzula species. Codon substitution models were employed to infer selective regimes acting on CenH3 in Luzula KEY RESULTS: In addition to the two previously published CenH3 sequences from L. nivea, 16 new CenH3 sequences have been isolated from 12 Luzula species. Two CenH3 isoforms in Luzula that originated by a duplication event prior to the divergence of analysed species were found. No signs of positive selection acting on CenH3 in Luzula were detected. Instead, evidence was found that selection on CenH3 of Luzula might have been relaxed. The results indicate that holokinetism itself may suppress centromere drive and, therefore, holokinetic chromosomes might have evolved as a defence against centromere drive. © The Author 2016. Published by Oxford University Press on behalf of

Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role.

Science.gov (United States)

Miklós, István; Zádori, Zoltán

2012-02-01

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (pHD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs.

Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution.

Directory of Open Access Journals (Sweden)

Stewart I Head

Full Text Available Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i an increased rate of decay of the twitch transient; (ii a fourfold increase in the rate of SR Ca2+ leak; (iii a threefold increase in the rate of SR Ca2+ pumping; and (iv enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments

ZP Domain Proteins in the Abalone Egg Coat Include a Paralog of VERL under Positive Selection That Binds Lysin and 18-kDa Sperm Proteins

Science.gov (United States)

Aagaard, Jan E.; Vacquier, Victor D.; MacCoss, Michael J.; Swanson, Willie J.

2010-01-01

Identifying fertilization molecules is key to our understanding of reproductive biology, yet only a few examples of interacting sperm and egg proteins are known. One of the best characterized comes from the invertebrate archeogastropod abalone (Haliotis spp.), where sperm lysin mediates passage through the protective egg vitelline envelope (VE) by binding to the VE protein vitelline envelope receptor for lysin (VERL). Rapid adaptive divergence of abalone lysin and VERL are an example of positive selection on interacting fertilization proteins contributing to reproductive isolation. Previously, we characterized a subset of the abalone VE proteins that share a structural feature, the zona pellucida (ZP) domain, which is common to VERL and the egg envelopes of vertebrates. Here, we use additional expressed sequence tag sequencing and shotgun proteomics to characterize this family of proteins in the abalone egg VE. We expand 3-fold the number of known ZP domain proteins present within the VE (now 30 in total) and identify a paralog of VERL (vitelline envelope zona pellucida domain protein [VEZP] 14) that contains a putative lysin-binding motif. We find that, like VERL, the divergence of VEZP14 among abalone species is driven by positive selection on the lysin-binding motif alone and that these paralogous egg VE proteins bind a similar set of sperm proteins including a rapidly evolving 18-kDa paralog of lysin, which may mediate sperm–egg fusion. This work identifies an egg coat paralog of VERL under positive selection and the candidate sperm proteins with which it may interact during abalone fertilization. PMID:19767347

Fishing destabilizes the biomass flow in the marine size spectrum.

Science.gov (United States)

Rochet, M-J; Benoît, E

2012-01-22

Fishing impacts on marine food webs are predicted by simulations of a size spectrum community model. In this model, predation is determined by predator and prey size and abundance, and drives predator growth and prey mortality. Fishing amplifies temporal oscillations in the biomass flow. Oscillations appear at lower fishing intensity and have wider amplitude when fishing is selective (removes a narrow size range) and/or when large fish are targeted, than when fishing is more balanced (catching a larger size range) or when small fish are targeted. A novel index of size diversity is developed, and is shown to be sensitive to both fishing intensity and selectivity. To avoid unstable food web dynamics with potential harmful consequences for fisheries, limiting both fishing intensity and selectivity might be an appropriate exploitation strategy.

Silencing, positive selection and parallel evolution: busy history of primate cytochromes C.

Science.gov (United States)

Pierron, Denis; Opazo, Juan C; Heiske, Margit; Papper, Zack; Uddin, Monica; Chand, Gopi; Wildman, Derek E; Romero, Roberto; Goodman, Morris; Grossman, Lawrence I

2011-01-01

Cytochrome c (cyt c) participates in two crucial cellular processes, energy production and apoptosis, and unsurprisingly is a highly conserved protein. However, previous studies have reported for the primate lineage (i) loss of the paralogous testis isoform, (ii) an acceleration and then a deceleration of the amino acid replacement rate of the cyt c somatic isoform, and (iii) atypical biochemical behavior of human cyt c. To gain insight into the cause of these major evolutionary events, we have retraced the history of cyt c loci among primates. For testis cyt c, all primate sequences examined carry the same nonsense mutation, which suggests that silencing occurred before the primates diversified. For somatic cyt c, maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded the same tree topology. The evolutionary analyses show that a fast accumulation of non-synonymous mutations (suggesting positive selection) occurred specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stems. Analysis of evolutionary changes using the 3D structure suggests they are focused on the respiratory chain rather than on apoptosis or other cyt c functions. In agreement with previous biochemical studies, our results suggest that silencing of the cyt c testis isoform could be linked with the decrease of primate reproduction rate. Finally, the evolution of cyt c in the two sister anthropoid groups leads us to propose that somatic cyt c evolution may be related both to COX evolution and to the convergent brain and body mass enlargement in these two anthropoid clades.

Silencing, positive selection and parallel evolution: busy history of primate cytochromes C.

Directory of Open Access Journals (Sweden)

Denis Pierron

Full Text Available Cytochrome c (cyt c participates in two crucial cellular processes, energy production and apoptosis, and unsurprisingly is a highly conserved protein. However, previous studies have reported for the primate lineage (i loss of the paralogous testis isoform, (ii an acceleration and then a deceleration of the amino acid replacement rate of the cyt c somatic isoform, and (iii atypical biochemical behavior of human cyt c. To gain insight into the cause of these major evolutionary events, we have retraced the history of cyt c loci among primates. For testis cyt c, all primate sequences examined carry the same nonsense mutation, which suggests that silencing occurred before the primates diversified. For somatic cyt c, maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded the same tree topology. The evolutionary analyses show that a fast accumulation of non-synonymous mutations (suggesting positive selection occurred specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stems. Analysis of evolutionary changes using the 3D structure suggests they are focused on the respiratory chain rather than on apoptosis or other cyt c functions. In agreement with previous biochemical studies, our results suggest that silencing of the cyt c testis isoform could be linked with the decrease of primate reproduction rate. Finally, the evolution of cyt c in the two sister anthropoid groups leads us to propose that somatic cyt c evolution may be related both to COX evolution and to the convergent brain and body mass enlargement in these two anthropoid clades.

Comparative Genomics of Smut Pathogens: Insights From Orphans and Positively Selected Genes Into Host Specialization

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Juliana Benevenuto

2018-04-01

Full Text Available Host specialization is a key evolutionary process for the diversification and emergence of new pathogens. However, the molecular determinants of host range are poorly understood. Smut fungi are biotrophic pathogens that have distinct and narrow host ranges based on largely unknown genetic determinants. Hence, we aimed to expand comparative genomics analyses of smut fungi by including more species infecting different hosts and to define orphans and positively selected genes to gain further insights into the genetics basis of host specialization. We analyzed nine lineages of smut fungi isolated from eight crop and non-crop hosts: maize, barley, sugarcane, wheat, oats, Zizania latifolia (Manchurian rice, Echinochloa colona (a wild grass, and Persicaria sp. (a wild dicot plant. We assembled two new genomes: Ustilago hordei (strain Uhor01 isolated from oats and U. tritici (strain CBS 119.19 isolated from wheat. The smut genomes were of small sizes, ranging from 18.38 to 24.63 Mb. U. hordei species experienced genome expansions due to the proliferation of transposable elements and the amount of these elements varied among the two strains. Phylogenetic analysis confirmed that Ustilago is not a monophyletic genus and, furthermore, detected misclassification of the U. tritici specimen. The comparison between smut pathogens of crop and non-crop hosts did not reveal distinct signatures, suggesting that host domestication did not play a dominant role in shaping the evolution of smuts. We found that host specialization in smut fungi likely has a complex genetic basis: different functional categories were enriched in orphans and lineage-specific selected genes. The diversification and gain/loss of effector genes are probably the most important determinants of host specificity.

Kinetics and selectivity of permanganate chemiluminescence: a study of hydroxyl and amino disubstituted benzene positional isomers.

Science.gov (United States)

Slezak, Teo; Smith, Zoe M; Adcock, Jacqui L; Hindson, Christopher M; Barnett, Neil W; Nesterenko, Pavel N; Francis, Paul S

2011-11-30

Examination of the chemiluminescence reactions of dihydroxybenzenes, aminophenols and phenylenediamines with acidic potassium permanganate has provided a new understanding of the relationships between analyte structure, reaction conditions, kinetics of the light-producing pathway and emission intensity, with broad implications for this widely utilised chemiluminescence detection system. Using a permanganate reagent prepared in a polyphosphate solution and adjusted to pH 2.5, large differences in the rate of reaction with different positional isomers were observed, with the meta-substituted forms reacting far slower and therefore exhibiting much lower chemiluminescence intensities in flow analysis systems. The preliminary partial reduction of permanganate to form significant concentrations of Mn(III) increased the rate of reaction with all analytes tested, resulting in comparable or (in the case of aminophenol and phenylenediamine) even greater emission intensities for the meta-isomers, demonstrating the opportunity to tune the selectivity of the reagent towards certain classes of compound or even specific positional isomers of the same compound. Using more acidic permanganate reagents, in which polyphosphates are not required, the discrepancy between the chemiluminescence intensities was still observed, but was less prominent due to the generally faster rates of reaction. The enhancement of these chemiluminescence reactions by on-line addition of formic acid or formaldehyde can in part also be attributed to the generation of significant pools of the key Mn(III) precursor to the emitting species. Copyright © 2011 Elsevier B.V. All rights reserved.

Analysis of seasonal position variation for selected GNSS sites in Poland using loading modelling and GRACE data

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Marcin Rajner

2017-07-01

Full Text Available In this study we compared weekly GNSS position time series with modelled values of crustal deformations on the basis of Gravity Recovery and Climate Experiment (GRACE data. The Global Navigation Satellite Systems (GNSS time series were taken from homogeneously reprocessed global network solutions within the International GNSS Service (IGS Reprocessing 1 project and from regional solutions performed by Warsaw University of Technology (WUT European Permanent Network (EPN Local Analysis Center (LAC within the EPN reprocessing project. Eight GNSS sites from the territory of Poland with observation timespans between 2.5 and 13 years were selected for this study. The Total Water Equivalent (TWE estimation from GRACE data was used to compute deformations using the Green's function formalism. High frequency components were removed from GRACE data to avoid aliasing problems. Since GRACE observes mainly the mass transport in continental storage of water, we also compared GRACE deformations and the GNSS position time series, with the deformations computed on the basis of a hydrosphere model. We used the output of Water GAP Hydrology Model (WGHM to compute deformations in the same manner as for the GRACE data. The WGHM gave slightly larger amplitudes than GNSS and GRACE. The atmospheric non-tidal loading effect was removed from GNSS position time series before comparing them with modelled deformations. The results confirmed that the major part of observed seasonal variations for GNSS vertical components can be attributed to the hydrosphere loading. The results for these components agree very well both in the amplitude and phase. The decrease in standard deviation of the residual GNSS position time series for vertical components corrected for the hydrosphere loading reached maximally 36% and occurred for all but one stations for both global and regional solutions. For horizontal components the amplitudes are about three times smaller than for vertical

Soft sweeps III: the signature of positive selection from recurrent mutation.

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Pleuni S Pennings

2006-12-01

Full Text Available Polymorphism data can be used to identify loci at which a beneficial allele has recently gone to fixation, given that an accurate description of the signature of selection is available. In the classical model that is used, a favored allele derives from a single mutational origin. This ignores the fact that beneficial alleles can enter a population recurrently by mutation during the selective phase. In this study, we present a combination of analytical and simulation results to demonstrate the effect of adaptation from recurrent mutation on summary statistics for polymorphism data from a linked neutral locus. We also analyze the power of standard neutrality tests based on the frequency spectrum or on linkage disequilibrium (LD under this scenario. For recurrent beneficial mutation at biologically realistic rates, we find substantial deviations from the classical pattern of a selective sweep from a single new mutation. Deviations from neutrality in the level of polymorphism and in the frequency spectrum are much less pronounced than in the classical sweep pattern. In contrast, for levels of LD, the signature is even stronger if recurrent beneficial mutation plays a role. We suggest a variant of existing LD tests that increases their power to detect this signature.

Sample Selection for Training Cascade Detectors.

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Vállez, Noelia; Deniz, Oscar; Bueno, Gloria

2015-01-01

Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

Positive selection in the SLC11A1 gene in the family Equidae

DEFF Research Database (Denmark)

Bayerova, Zuzana; Janova, Eva; Matiasovic, Jan

2016-01-01

Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes...... a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans...... and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence...

A Review Relevant to Turbomachinery Flows

Directory of Open Access Journals (Sweden)

James P. Johnston

1998-01-01

“buoyancy” currents in cases where density gradients occur. Turbulence modification involves reduction (stabilization or increase (destabilization of turbulent Reynolds stresses by Coriolis forces; effects which areof special importance for the understanding and prediction of flows in radial and mixed flow pump and compressor rotors. Stabilization/destabilization effects are discussed by a selective review of the basic research literature on flows in straight, radial, rotating channels and diffusers.

Modified Borohydrides for Reversible Hydrogen Storage (2)

International Nuclear Information System (INIS)

Ming Au

2006-01-01

This paper reports the results in the effort to destabilize lithium borohydride for reversible hydrogen storage. A number of metals, metal hydrides, metal chlorides and complex hydrides were selected and evaluated as the destabilization agents for reducing de-hydriding temperature and generating de-hydriding-re-hydriding reversibility. It is found that some additives are effective. The Raman spectroscopic analysis shows the change of B-H binding nature. (authors)

Sample Selection for Training Cascade Detectors.

Directory of Open Access Journals (Sweden)

Noelia Vállez

Full Text Available Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

Detecting Positive Selection of Korean Native Goat Populations Using Next-Generation Sequencing

Science.gov (United States)

Lee, Wonseok; Ahn, Sojin; Taye, Mengistie; Sung, Samsun; Lee, Hyun-Jeong; Cho, Seoae; Kim, Heebal

2016-01-01

Goats (Capra hircus) are one of the oldest species of domesticated animals. Native Korean goats are a particularly interesting group, as they are indigenous to the area and were raised in the Korean peninsula almost 2,000 years ago. Although they have a small body size and produce low volumes of milk and meat, they are quite resistant to lumbar paralysis. Our study aimed to reveal the distinct genetic features and patterns of selection in native Korean goats by comparing the genomes of native Korean goat and crossbred goat populations. We sequenced the whole genome of 15 native Korean goats and 11 crossbred goats using next-generation sequencing (Illumina platform) to compare the genomes of the two populations. We found decreased nucleotide diversity in the native Korean goats compared to the crossbred goats. Genetic structural analysis demonstrated that the native Korean goat and crossbred goat populations shared a common ancestry, but were clearly distinct. Finally, to reveal the native Korean goat’s selective sweep region, selective sweep signals were identified in the native Korean goat genome using cross-population extended haplotype homozygosity (XP-EHH) and a cross-population composite likelihood ratio test (XP-CLR). As a result, we were able to identify candidate genes for recent selection, such as the CCR3 gene, which is related to lumbar paralysis resistance. Combined with future studies and recent goat genome information, this study will contribute to a thorough understanding of the native Korean goat genome. PMID:27989103

Detecting Positive Selection of Korean Native Goat Populations Using Next-Generation Sequencing.

Science.gov (United States)

Lee, Wonseok; Ahn, Sojin; Taye, Mengistie; Sung, Samsun; Lee, Hyun-Jeong; Cho, Seoae; Kim, Heebal

2016-12-01

Goats ( Capra hircus ) are one of the oldest species of domesticated animals. Native Korean goats are a particularly interesting group, as they are indigenous to the area and were raised in the Korean peninsula almost 2,000 years ago. Although they have a small body size and produce low volumes of milk and meat, they are quite resistant to lumbar paralysis. Our study aimed to reveal the distinct genetic features and patterns of selection in native Korean goats by comparing the genomes of native Korean goat and crossbred goat populations. We sequenced the whole genome of 15 native Korean goats and 11 crossbred goats using next-generation sequencing (Illumina platform) to compare the genomes of the two populations. We found decreased nucleotide diversity in the native Korean goats compared to the crossbred goats. Genetic structural analysis demonstrated that the native Korean goat and crossbred goat populations shared a common ancestry, but were clearly distinct. Finally, to reveal the native Korean goat's selective sweep region, selective sweep signals were identified in the native Korean goat genome using cross-population extended haplotype homozygosity (XP-EHH) and a cross-population composite likelihood ratio test (XP-CLR). As a result, we were able to identify candidate genes for recent selection, such as the CCR3 gene, which is related to lumbar paralysis resistance. Combined with future studies and recent goat genome information, this study will contribute to a thorough understanding of the native Korean goat genome.

Natural Selection in Virulence Genes of Francisella tularensis.

Science.gov (United States)

Gunnell, Mark K; Robison, Richard A; Adams, Byron J

2016-06-01

A fundamental tenet of evolution is that alleles that are under negative selection are often deleterious and confer no evolutionary advantage. Negatively selected alleles are removed from the gene pool and are eventually extinguished from the population. Conversely, alleles under positive selection do confer an evolutionary advantage and lead to an increase in the overall fitness of the organism. These alleles increase in frequency until they eventually become fixed in the population. Francisella tularensis is a zoonotic pathogen and a potential biothreat agent. The most virulent type of F. tularensis, Type A, is distributed across North America with Type A.I occurring mainly in the east and Type A.II appearing mainly in the west. F. tularensis is thought to be a genome in decay (losing genes) because of the relatively large number of pseudogenes present in its genome. We hypothesized that the observed frequency of gene loss/pseudogenes may be an artifact of evolution in response to a changing environment, and that genes involved in virulence should be under strong positive selection. To test this hypothesis, we sequenced and compared whole genomes of Type A.I and A.II isolates. We analyzed a subset of virulence and housekeeping genes from several F. tularensis subspecies genomes to ascertain the presence and extent of positive selection. Eleven previously identified virulence genes were screened for positive selection along with 10 housekeeping genes. Analyses of selection yielded one housekeeping gene and 7 virulence genes which showed significant evidence of positive selection at loci implicated in cell surface structures and membrane proteins, metabolism and biosynthesis, transcription, translation and cell separation, and substrate binding and transport. Our results suggest that while the loss of functional genes through disuse could be accelerated by negative selection, the genome decay in Francisella could also be the byproduct of adaptive evolution

Selective loss of Purkinje cells in a patient with anti-gliadin-antibody-positive autoimmune cerebellar ataxia

Directory of Open Access Journals (Sweden)

Hasegawa Akira

2011-02-01

Full Text Available Abstract The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum. In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

Genomic selection in plant breeding.

Science.gov (United States)

Newell, Mark A; Jannink, Jean-Luc

2014-01-01

Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor and major marker effects. Thus, the GEBV may capture more of the genetic variation for the particular trait under selection.

Identification of recently selected mutations driven by artificial selection in hanwoo (korean cattle).

Science.gov (United States)

Lim, Dajeong; Gondro, Cedric; Park, Hye Sun; Cho, Yong Min; Chai, Han Ha; Seong, Hwan Hoo; Yang, Bo Suk; Hong, Seong Koo; Chang, Won Kyung; Lee, Seung Hwan

2013-05-01

Hanwoo have been subjected over the last seventy years to intensive artificial selection with the aim of improving meat production traits such as marbling and carcass weight. In this study, we performed a signature of selection analysis to identify recent positive selected regions driven by a long-term artificial selection process called a breeding program using whole genome SNP data. In order to investigate homozygous regions across the genome, we estimated iES (integrated Extended Haplotype Homozygosity SNP) for the each SNPs. As a result, we identified two highly homozygous regions that seem to be strong and/or recent positive selection. Five genes (DPH5, OLFM3, S1PR1, LRRN1 and CRBN) were included in this region. To go further in the interpretation of the observed signatures of selection, we subsequently concentrated on the annotation of differentiated genes defined according to the iES value of SNPs localized close or within them. We also described the detection of the adaptive evolution at the molecular level for the genes of interest. As a result, this analysis also led to the identification of OLFM3 as having a strong signal of selection in bovine lineage. The results of this study indicate that artificial selection which might have targeted most of these genes was mainly oriented towards improvement of meat production.

Identification of Recently Selected Mutations Driven by Artificial Selection in Hanwoo (Korean Cattle

Directory of Open Access Journals (Sweden)

Dajeong Lim

2013-05-01

Full Text Available Hanwoo have been subjected over the last seventy years to intensive artificial selection with the aim of improving meat production traits such as marbling and carcass weight. In this study, we performed a signature of selection analysis to identify recent positive selected regions driven by a long-term artificial selection process called a breeding program using whole genome SNP data. In order to investigate homozygous regions across the genome, we estimated iES (integrated Extended Haplotype Homozygosity SNP for the each SNPs. As a result, we identified two highly homozygous regions that seem to be strong and/or recent positive selection. Five genes (DPH5, OLFM3, S1PR1, LRRN1 and CRBN were included in this region. To go further in the interpretation of the observed signatures of selection, we subsequently concentrated on the annotation of differentiated genes defined according to the iES value of SNPs localized close or within them. We also described the detection of the adaptive evolution at the molecular level for the genes of interest. As a result, this analysis also led to the identification of OLFM3 as having a strong signal of selection in bovine lineage. The results of this study indicate that artificial selection which might have targeted most of these genes was mainly oriented towards improvement of meat production.

Selectivity improvement of positive photoionization ion mobility spectrometry for rapid detection of organophosphorus pesticides by switching dopant concentration.

Science.gov (United States)

Zhou, Qinghua; Li, Jia; Wang, Bin; Wang, Shuang; Li, Haiyang; Chen, Jinyuan

2018-01-01

Ion mobility spectrometry (IMS) opened a potential avenue for the rapid detection of organophosphorus pesticides (OPPs), though an improved selectivity of stand-alone IMS was still in high demand. In this study, a stand-alone positive photoionization ion mobility spectrometry (PP-IMS) apparatus was constructed for the rapid detection of OPPs with acetone as dopant. The photoionization of acetone molecules was induced by the ultraviolet irradiation to produce the reactant ions (Ac) 2 H + , which were employed to ionize the OPPs including fenthion, imidan, phosphamidon, dursban, dimethoate and isocarbophos via the proton transfer reaction. Due to the difference in proton affinity, the tested OPPs exhibited the different dopant-dependent manners. Based on this observation, the switching of dopant concentration was implemented to improve the selectivity of PP-IMS for OPPs detection. For instance, a mixture of fenthion, dursban and dimethoate was tested. By switching the concentration of doped acetone from 0.07 to 2.33 to 19.94mgL -1 , the ion peaks of fenthion and dursban were inhibited in succession, achieving the selective detection of dimethoate at last. In addition, another mixture of imidan and phosphamidon was initially detected by PP-IMS with a dose of 0.07mgL -1 acetone, indicating that their ion peaks were severely overlapped; when the concentration of doped acetone was switched to 19.94mgL -1 , the inhibition of imidan signals promised the accurate identification of phosphamidon in mixture. Finally, the PP-IMS in combination of switching dopant concentration was applied to detect the mixed fenthion, dursban and dimethoate in Chinese cabbage, demonstrating the applicability of proposed method to real samples. Copyright © 2017. Published by Elsevier B.V.

Factors associated with performing tuberculosis screening of HIV-positive patients in Ghana: LASSO-based predictor selection in a large public health data set

Directory of Open Access Journals (Sweden)

Susanne Mueller-Using

2016-07-01

Full Text Available Abstract Background The purpose of this study is to propose the Least Absolute Shrinkage and Selection Operators procedure (LASSO as an alternative to conventional variable selection models, as it allows for easy interpretation and handles multicollinearities. We developed a model on the basis of LASSO-selected parameters in order to link associated demographical, socio-economical, clinical and immunological factors to performing tuberculosis screening in HIV-positive patients in Ghana. Methods Applying the LASSO method and multivariate logistic regression analysis on a large public health data set, we selected relevant predictors related to tuberculosis screening. Results One Thousand Ninety Five patients infected with HIV were enrolled into this study with 691 (63.2 % of them having tuberculosis screening documented in their patient folders. Predictors found to be significantly associated with performance of tuberculosis screening can be classified into factors related to the clinician’s perception of the clinical state, as well as those related to PLHIV’s awareness. These factors include newly diagnosed HIV infections (n = 354 (32.42 %, aOR 1.84, current CD4+ T cell count (aOR 0.92, non-availability of HIV type (n = 787 (72.07 %, aOR 0.56, chronic cough (n = 32 (2.93 %, aOR 5.07, intake of co-trimoxazole (n = 271 (24.82 %, aOR 2.31, vitamin supplementation (n = 220 (20.15 %, aOR 2.64 as well as the use of mosquito bed nets (n = 613 (56.14 %, aOR 1.53. Conclusions Accelerated TB screening among newly diagnosed HIV-patients indicates that application of the WHO screening form for intensifying tuberculosis case finding among HIV-positive individuals in resource-limited settings is increasingly adopted. However, screening for TB in PLHIV is still impacted by clinician’s perception of patient’s health state and PLHIV’s health awareness. Education of staff, counselling of PLHIV and sufficient financing are

Finding Direction in the Search for Selection.

Science.gov (United States)

Thiltgen, Grant; Dos Reis, Mario; Goldstein, Richard A

2017-01-01

Tests for positive selection have mostly been developed to look for diversifying selection where change away from the current amino acid is often favorable. However, in many cases we are interested in directional selection where there is a shift toward specific amino acids, resulting in increased fitness in the species. Recently, a few methods have been developed to detect and characterize directional selection on a molecular level. Using the results of evolutionary simulations as well as HIV drug resistance data as models of directional selection, we compare two such methods with each other, as well as against a standard method for detecting diversifying selection. We find that the method to detect diversifying selection also detects directional selection under certain conditions. One method developed for detecting directional selection is powerful and accurate for a wide range of conditions, while the other can generate an excessive number of false positives.

Impeller in Precessing Motion

Directory of Open Access Journals (Sweden)

Yoshiki Yoshida

2001-01-01

destabilizing in the region of negative precessing speed ratio (-0.3<Ω/ω<0, at the design flow rate; (2 At reduced flow rate, the destabilizing fluid force moments occurred at small positive precessing speed ratio (0.2<Ω/ω<0.4; (3 From the comparison of direct measured fluid force moments with those estimated from the unsteady pressure measured on the front and back casing walls, it was found that the destabilizing moments in the backward precession are mainly caused by the fluid forces on the front surface of the present impeller, where there is large clearance between the back shroud and casing.

Directional and balancing selection in human beta-defensins.

Science.gov (United States)

Hollox, Edward J; Armour, John A L

2008-04-16

In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93), is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.

Kaiser Engineers Hanford internal position paper -- Project W-236A, Multi-function Waste Tank Facility -- Peer reviews of selected activities

International Nuclear Information System (INIS)

Stine, M.D.

1995-01-01

The purpose of this paper is to develop and document a proposed position on the performance of independent peer reviews on selected design and analysis components of the Title 1 [Preliminary] and Title 2 [Final] design phases of the Multi-Function Waste Tank Facility [MWTF] project. An independent, third-party peer review is defined as a documented critical review of documents, data, designs, design inputs, tests, calculations, or related materials. The peer review should be conducted by persons independent of those who performed the work, but who are technically qualified to perform the original work. The peer review is used to assess the validity of assumptions and functional requirements, to assess the appropriateness and logic of selected methodologies and design inputs, and to verify calculations, analyses and computer software. The peer review can be conducted at the end of the design activity, at specific stages of the design process, or continuously and concurrently with the design activity. This latter method is often referred to as ''Continuous Peer Review.''

Selection into Labor Force and Gender Unemployment Gaps

OpenAIRE

Alena Bicakova

2014-01-01

This paper sets the groundwork for analysis of the effect of selection into labor force on gender unemployment gaps. We derive the Manski bounds for gender unemployment gaps in 21 EU countries and show that in addition to the positive selection documented in the gender wage gap research, there is also evidence of negative selection into the labor force among women after childbirth. While positive selection of women into the labor force leads to downward bias in gender unemployment gaps, negat...

Trade-off between positive and negative design of protein stability: from lattice models to real proteins.

Directory of Open Access Journals (Sweden)

Orly Noivirt-Brik

2009-12-01

Full Text Available Two different strategies for stabilizing proteins are (i positive design in which the native state is stabilized and (ii negative design in which competing non-native conformations are destabilized. Here, the circumstances under which one strategy might be favored over the other are explored in the case of lattice models of proteins and then generalized and discussed with regard to real proteins. The balance between positive and negative design of proteins is found to be determined by their average "contact-frequency", a property that corresponds to the fraction of states in the conformational ensemble of the sequence in which a pair of residues is in contact. Lattice model proteins with a high average contact-frequency are found to use negative design more than model proteins with a low average contact-frequency. A mathematical derivation of this result indicates that it is general and likely to hold also for real proteins. Comparison of the results of correlated mutation analysis for real proteins with typical contact-frequencies to those of proteins likely to have high contact-frequencies (such as disordered proteins and proteins that are dependent on chaperonins for their folding indicates that the latter tend to have stronger interactions between residues that are not in contact in their native conformation. Hence, our work indicates that negative design is employed when insufficient stabilization is achieved via positive design owing to high contact-frequencies.

Selective biosensing of Staphylococcus aureus using chitosan quantum dots

Science.gov (United States)

Abdelhamid, Hani Nasser; Wu, Hui-Fen

2018-01-01

Selective biosensing of Staphylococcus aureus (S. aureus) using chitosan modified quantum dots (CTS@CdS QDs) in the presence of hydrogen peroxide is reported. The method is based on the intrinsic positive catalase activity of S. aureus. CTS@CdS quantum dots provide high dispersion in aqueous media with high fluorescence emission. Staphylococcus aureus causes a selective quenching of the fluorescence emission of CTS@CdS QDs in the presence of H2O2 compared to other pathogens such as Escherichia coli and Pseudomonas aeruginosa. The intrinsic enzymatic character of S. aureus (catalase positive) offers selective and fast biosensing. The present method is highly selective for positive catalase species and requires no expensive reagents such as antibodies, aptamers or microbeads. It could be extended for other species that are positive catalase.

A high efficiency gene disruption strategy using a positive-negative split selection marker and electroporation for Fusarium oxysporum.

Science.gov (United States)

Liang, Liqin; Li, Jianqiang; Cheng, Lin; Ling, Jian; Luo, Zhongqin; Bai, Miao; Xie, Bingyan

2014-11-01

The Fusarium oxysporum species complex consists of fungal pathogens that cause serial vascular wilt disease on more than 100 cultivated species throughout the world. Gene function analysis is rapidly becoming more and more important as the whole-genome sequences of various F. oxysporum strains are being completed. Gene-disruption techniques are a common molecular tool for studying gene function, yet are often a limiting step in gene function identification. In this study we have developed a F. oxysporum high-efficiency gene-disruption strategy based on split-marker homologous recombination cassettes with dual selection and electroporation transformation. The method was efficiently used to delete three RNA-dependent RNA polymerase (RdRP) genes. The gene-disruption cassettes of three genes can be constructed simultaneously within a short time using this technique. The optimal condition for electroporation is 10μF capacitance, 300Ω resistance, 4kV/cm field strength, with 1μg of DNA (gene-disruption cassettes). Under these optimal conditions, we were able to obtain 95 transformants per μg DNA. And after positive-negative selection, the transformants were efficiently screened by PCR, screening efficiency averaged 85%: 90% (RdRP1), 85% (RdRP2) and 77% (RdRP3). This gene-disruption strategy should pave the way for high throughout genetic analysis in F. oxysporum. Copyright © 2014 Elsevier GmbH. All rights reserved.

Directional and balancing selection in human beta-defensins

Directory of Open Access Journals (Sweden)

Armour John AL

2008-04-01

Full Text Available Abstract Background In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. Results We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93, is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Conclusion Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.

Effect of Positive Training on Positive Psychological States (Character Strengths of Female High School Students

Directory of Open Access Journals (Sweden)

Ali Farnam

2017-05-01

Full Text Available psychological states of female students in second and third grades of high school. The research method was quasi-experimental with pre-test, post-test and follow-up. The sample consisted of forty students selected randomly in two groups (twenty students in each group. To collect data, Positive Psychological State Inventory (Rajaei, Khuy Nzhad and Nesaei was used. The experimental group received ninety minute positive training sessions (for two months and the control group did not receive treatment. The results of analysis  of covariance showed that positive training had positive effects on positive psychological states (trust in God, optimism, self-efficacy, duty, sense of control, targeted, hope, satisfaction with life, meaningful life, pleasant, sociability, self-esteem and self-worth, sense of peace, gratitude, and forgiveness among adolescents  both in the post  and follow-up tests

Patterns of Nucleotide Diversity at the Regions Encompassing the Drosophila Insulin-Like Peptide (dilp) Genes: Demography vs. Positive Selection in Drosophila melanogaster

Science.gov (United States)

Guirao-Rico, Sara; Aguadé, Montserrat

2013-01-01

In Drosophila, the insulin-signaling pathway controls some life history traits, such as fertility and lifespan, and it is considered to be the main metabolic pathway involved in establishing adult body size. Several observations concerning variation in body size in the Drosophila genus are suggestive of its adaptive character. Genes encoding proteins in this pathway are, therefore, good candidates to have experienced adaptive changes and to reveal the footprint of positive selection. The Drosophila insulin-like peptides (DILPs) are the ligands that trigger the insulin-signaling cascade. In Drosophila melanogaster, there are several peptides that are structurally similar to the single mammalian insulin peptide. The footprint of recent adaptive changes on nucleotide variation can be unveiled through the analysis of polymorphism and divergence. With this aim, we have surveyed nucleotide sequence variation at the dilp1-7 genes in a natural population of D. melanogaster. The comparison of polymorphism in D. melanogaster and divergence from D. simulans at different functional classes of the dilp genes provided no evidence of adaptive protein evolution after the split of the D. melanogaster and D. simulans lineages. However, our survey of polymorphism at the dilp gene regions of D. melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events. PMID:23308258

Clients' experiences of HIV positive status disclosure to sexual ...

African Journals Online (AJOL)

The purpose of the study was to describe the experiences of HIV positive clients as they disclose their HIV positive status to their sexual partners. A qualitative descriptive and phenomenological design was used. Purposive sampling was used to select 15 HIV positive clients to participate in the study. Semi-structured ...

Scalability Optimization of Seamless Positioning Service

Directory of Open Access Journals (Sweden)

Juraj Machaj

2016-01-01

Full Text Available Recently positioning services are getting more attention not only within research community but also from service providers. From the service providers point of view positioning service that will be able to work seamlessly in all environments, for example, indoor, dense urban, and rural, has a huge potential to open new markets. However, such system does not only need to provide accurate position estimates but have to be scalable and resistant to fake positioning requests. In the previous works we have proposed a modular system, which is able to provide seamless positioning in various environments. The system automatically selects optimal positioning module based on available radio signals. The system currently consists of three positioning modules—GPS, GSM based positioning, and Wi-Fi based positioning. In this paper we will propose algorithm which will reduce time needed for position estimation and thus allow higher scalability of the modular system and thus allow providing positioning services to higher amount of users. Such improvement is extremely important, for real world application where large number of users will require position estimates, since positioning error is affected by response time of the positioning server.

Prediction-Oriented Marker Selection (PROMISE): With Application to High-Dimensional Regression.

Science.gov (United States)

Kim, Soyeon; Baladandayuthapani, Veerabhadran; Lee, J Jack

2017-06-01

In personalized medicine, biomarkers are used to select therapies with the highest likelihood of success based on an individual patient's biomarker/genomic profile. Two goals are to choose important biomarkers that accurately predict treatment outcomes and to cull unimportant biomarkers to reduce the cost of biological and clinical verifications. These goals are challenging due to the high dimensionality of genomic data. Variable selection methods based on penalized regression (e.g., the lasso and elastic net) have yielded promising results. However, selecting the right amount of penalization is critical to simultaneously achieving these two goals. Standard approaches based on cross-validation (CV) typically provide high prediction accuracy with high true positive rates but at the cost of too many false positives. Alternatively, stability selection (SS) controls the number of false positives, but at the cost of yielding too few true positives. To circumvent these issues, we propose prediction-oriented marker selection (PROMISE), which combines SS with CV to conflate the advantages of both methods. Our application of PROMISE with the lasso and elastic net in data analysis shows that, compared to CV, PROMISE produces sparse solutions, few false positives, and small type I + type II error, and maintains good prediction accuracy, with a marginal decrease in the true positive rates. Compared to SS, PROMISE offers better prediction accuracy and true positive rates. In summary, PROMISE can be applied in many fields to select regularization parameters when the goals are to minimize false positives and maximize prediction accuracy.

Modelling News Media Use. Positing and applying the MC/GC model to the analysis of media use in everyday life and crisis situations

DEFF Research Database (Denmark)

Westlund, Oscar; Ghersetti, Marina

2014-01-01

The contemporary mediascape offers a plethora of news media and social media, which people can turn to in everyday life and during a crisis. The characteristics of media vary, providing different logics and affordances, and occupying different niches in time and space (medium-centric (MC) approach......). Generations develop routinized media usage patterns in the formative phases of their lives, which they often maintain in their daily habits in everyday life (generation-centric (GC) approach). Crisis events in the vicinity, such as gas emissions, terrorist attacks, pandemics and earthquakes, presumably ignite...... an augmented interest for information and news on the events that may cause a destabilization of established media usage routines. This article aims to conceptualize, describe and explain how four generations envision their media use during such crises. The article posits the MC/GC-model, a 2x2 matrix...

Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase

DEFF Research Database (Denmark)

Petersen, Nikolaj H T; Olsen, Ole D; Groth-Pedersen, Line

2013-01-01

Lysosomal membrane permeabilization and subsequent cell death may prove useful in cancer treatment, provided that cancer cell lysosomes can be specifically targeted. Here, we identify acid sphingomyelinase (ASM) inhibition as a selective means to destabilize cancer cell lysosomes. Lysosome......-destabilizing experimental anticancer agent siramesine inhibits ASM by interfering with the binding of ASM to its essential lysosomal cofactor, bis(monoacylglycero)phosphate. Like siramesine, several clinically relevant ASM inhibitors trigger cancer-specific lysosomal cell death, reduce tumor growth in vivo, and revert...

Flow Regime Destabilizing Effect on Fluid elastic Instability of Tube Array Preferentially Flexible to the Flow Direction

Energy Technology Data Exchange (ETDEWEB)

Lee, Kanghee; Shin, Changhwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Olala, Stephen; Mureithi, Njuki [BWC/AECL/NSERC Chair of Fluid-Structure Interaction, Ecole Polytechnique, Montreal (Canada)

2015-05-15

U bend region of operating SG is excited by the inclined cross flow due to the gradual change of hydraulic resistance force. The effect of tube array's flexibility direction on FEI is investigated by Khalvatti for rotated triangular tube in single phase (air) cross flow. He showed that FEI strongly depend on the flexibility angle. Reducing bundle flexibility to the flow direction ranging from 90 (out-of-flow direction) to 0 (in-flow direction) degree has a nonlinearly-varying stabilizing effect. Joly studies the same problem under high void fraction in two phase cross flow over 70 % to 90 %. With the Joly's experimental work, there is oddly low-valued Conner's constant in case of higher degree of angle of attack. This gives the motivation to our experimental study for fluid elastic instability of tube array in two phase cross flow. As the flow rate goes up, tube response was measured for each steady state flow condition by the strain gauge. Damping, peak frequency, and the critical velocity were estimated from the response spectrum. It seems that the flow regime for high void fraction can destabilize tube array with preferential flexibility over 60 degree. Because an intermittent flow is inherently unstable compared to the uniform bubbly flow, thus out-of-flow motion of tubes can be more fragile to the unstably rising intermittent flow. From the visual inspection, lateral tube motion seems to block the flow path periodically. Enlarged bubble in an intermittent flow regime can be squeezed-up at the flow gap between tubes.

Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment.

Science.gov (United States)

Sohn, Peter Dongmin; Tracy, Tara E; Son, Hye-In; Zhou, Yungui; Leite, Renata E P; Miller, Bruce L; Seeley, William W; Grinberg, Lea T; Gan, Li

2016-06-29

Neurons are highly polarized cells in which asymmetric axonal-dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of Alzheimer's disease (AD) and other neurodegenerative disorders. The cytoskeletal network in the axon initial segment (AIS) forms a barrier between the axon and the somatodentritic compartment, contributing to axonal retention of tau. Although perturbation of the AIS cytoskeleton has been implicated in neurological disorders, the molecular triggers and functional consequence of AIS perturbation are incompletely understood. Here we report that tau acetylation and consequent destabilization of the AIS cytoskeleton promote the somatodendritic mislocalization of tau. AIS cytoskeletal proteins, including ankyrin G and βIV-spectrin, were downregulated in AD brains and negatively correlated with an increase in tau acetylated at K274 and K281. AIS proteins were also diminished in transgenic mice expressing tauK274/281Q, a tau mutant that mimics K274 and K281 acetylation. In primary neuronal cultures, the tauK274/281Q mutant caused hyperdynamic microtubules (MTs) in the AIS, shown by live-imaging of MT mobility and fluorescence recovery after photobleaching. Using photoconvertible tau constructs, we found that axonal tauK274/281Q was missorted into the somatodendritic compartment. Stabilizing MTs with epothilone D to restore the cytoskeletal barrier in the AIS prevented tau mislocalization in primary neuronal cultures. Together, these findings demonstrate that tau acetylation contributes to the pathogenesis of neurodegenerative disease by compromising the cytoskeletal sorting machinery in the AIS.

The positive impact of women's employment on divorce: Context, selection, or anticipation?

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Daniele Vignoli

2018-03-01

Full Text Available Background: Empirical findings regarding the impact of women's employment on divorce are mixed. One explanation is that the effects are moderated by the country context. Another is that previous studies have failed to account for unobserved factors that introduce bias into the estimated effects. Studies also rarely consider possible anticipatory employment behavior on the part of women who are thinking of divorce. Objective: The aim of this study is to deepen our understanding of the nexus between women's employment and divorce in a comparative perspective. Methods: We adopt an analytical strategy that allows us to account for selection and anticipation mechanisms. Namely, we estimate marital disruption and employment jointly, and monitor the timing of divorce after employment entry. This approach is implemented using micro-level data for Germany, Hungary, Italy, and Poland. Results: We find that women's employment facilitates marital disruption in Italy and Poland, but not in Germany and Hungary. We also show that selection effects play out differently in different contexts. Finally, we notice traces of anticipatory behavior in Italy. Contribution: We conclude that women's employment is less likely to be linked to divorce in countries with easier access to divorce and in countries with more generous financial support for families and single mothers, which in turn makes women less reliant on the market. With this study we hope to encourage future researchers to consider the potentially distorting effects of selection and anticipation strategies in (comparative divorce research.

multiangulation position estimation performance analysis using

African Journals Online (AJOL)

HOD

multiangulation PE error is 50% lower than that of the directional rotating antenna system. Furthermore, the ... system is an example of a wireless positioning system that has ..... Table 2: PE error for some selection source locations. No. Range ...

Exploring evidence of positive selection reveals genetic basis of meat quality traits in Berkshire pigs through whole genome sequencing.

Science.gov (United States)

Jeong, Hyeonsoo; Song, Ki-Duk; Seo, Minseok; Caetano-Anollés, Kelsey; Kim, Jaemin; Kwak, Woori; Oh, Jae-Don; Kim, EuiSoo; Jeong, Dong Kee; Cho, Seoae; Kim, Heebal; Lee, Hak-Kyo

2015-08-20

Natural and artificial selection following domestication has led to the existence of more than a hundred pig breeds, as well as incredible variation in phenotypic traits. Berkshire pigs are regarded as having superior meat quality compared to other breeds. As the meat production industry seeks selective breeding approaches to improve profitable traits such as meat quality, information about genetic determinants of these traits is in high demand. However, most of the studies have been performed using trained sensory panel analysis without investigating the underlying genetic factors. Here we investigate the relationship between genomic composition and this phenotypic trait by scanning for signatures of positive selection in whole-genome sequencing data. We generated genomes of 10 Berkshire pigs at a total of 100.6 coverage depth, using the Illumina Hiseq2000 platform. Along with the genomes of 11 Landrace and 13 Yorkshire pigs, we identified genomic variants of 18.9 million SNVs and 3.4 million Indels in the mapped regions. We identified several associated genes related to lipid metabolism, intramuscular fatty acid deposition, and muscle fiber type which attribute to pork quality (TG, FABP1, AKIRIN2, GLP2R, TGFBR3, JPH3, ICAM2, and ERN1) by applying between population statistical tests (XP-EHH and XP-CLR). A statistical enrichment test was also conducted to detect breed specific genetic variation. In addition, de novo short sequence read assembly strategy identified several candidate genes (SLC25A14, IGF1, PI4KA, CACNA1A) as also contributing to lipid metabolism. Results revealed several candidate genes involved in Berkshire meat quality; most of these genes are involved in lipid metabolism and intramuscular fat deposition. These results can provide a basis for future research on the genomic characteristics of Berkshire pigs.

5th International Symposium on Positive Systems

CERN Document Server

Farina, Lorenzo; Setola, Roberto; Germani, Alfredo

2017-01-01

This book presents high-quality original contributions on positive systems, including topics such as: monotone dynamical systems in mathematical biology and game theory; mathematical developments for networked systems in biology, chemistry and the social sciences; linear and nonlinear positive operators; dynamical analysis, observation and control of positive distributed parameter systems; stochastic realization theory; biological systems with positive variables and positive controls; iterated function systems; nonnegative dynamic processes; and dimensioning problems for collaborative systems. The book comprises a selection of the best papers presented at the POSTA 2016, the 5th International Symposium on Positive Systems, which was held in Rome, Italy, in September 2016. This conference series represents a targeted response to the growing need for research that reports on and critically discusses a wide range of topics concerning the theory and applications of positive systems.

Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

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Yoichiro Shibata

2012-06-01

Full Text Available Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

Response to Comment on "Positive Selection of Tyrosine Loss in Metazoan Evolution"

DEFF Research Database (Denmark)

Tan, Chris Soon Heng; Schoof, Erwin; Creixell, Pau

2011-01-01

Su et al. claim guanine-cytosine (GC) content variation can largely explain the observed tyrosine frequency variation, independent of adaptive evolution of cell-signaling complexity. We found that GC content variation, in the absence of selection for amino acid changes, can only maximally account...

Functional conservation of nucleosome formation selectively biases presumably neutral molecular variation in yeast genomes.

Science.gov (United States)

Babbitt, Gregory A; Cotter, C R

2011-01-01

One prominent pattern of mutational frequency, long appreciated in comparative genomics, is the bias of purine/pyrimidine conserving substitutions (transitions) over purine/pyrimidine altering substitutions (transversions). Traditionally, this transitional bias has been thought to be driven by the underlying rates of DNA mutation and/or repair. However, recent sequencing studies of mutation accumulation lines in model organisms demonstrate that substitutions generally do not accumulate at rates that would indicate a transitional bias. These observations have called into question a very basic assumption of molecular evolution; that naturally occurring patterns of molecular variation in noncoding regions accurately reflect the underlying processes of randomly accumulating neutral mutation in nuclear genomes. Here, in Saccharomyces yeasts, we report a very strong inverse association (r = -0.951, P < 0.004) between the genome-wide frequency of substitutions and their average energetic effect on nucleosome formation, as predicted by a structurally based energy model of DNA deformation around the nucleosome core. We find that transitions occurring at sites positioned nearest the nucleosome surface, which are believed to function most importantly in nucleosome formation, alter the deformation energy of DNA to the nucleosome core by only a fraction of the energy changes typical of most transversions. When we examined the same substitutions set against random background sequences as well as an existing study reporting substitutions arising in mutation accumulation lines of Saccharomyces cerevisiae, we failed to find a similar relationship. These results support the idea that natural selection acting to functionally conserve chromatin organization may contribute significantly to genome-wide transitional bias, even in noncoding regions. Because nucleosome core structure is highly conserved across eukaryotes, our observations may also help to further explain locally elevated

Lateral position detection and control for friction stir systems

Science.gov (United States)

Fleming, Paul; Lammlein, David; Cook, George E.; Wilkes, Don Mitchell; Strauss, Alvin M.; Delapp, David; Hartman, Daniel A.

2010-12-14

A friction stir system for processing at least a first workpiece includes a spindle actuator coupled to a rotary tool comprising a rotating member for contacting and processing the first workpiece. A detection system is provided for obtaining information related to a lateral alignment of the rotating member. The detection system comprises at least one sensor for measuring a force experienced by the rotary tool or a parameter related to the force experienced by the rotary tool during processing, wherein the sensor provides sensor signals. A signal processing system is coupled to receive and analyze the sensor signals and determine a lateral alignment of the rotating member relative to a selected lateral position, a selected path, or a direction to decrease a lateral distance relative to the selected lateral position or selected path. In one embodiment, the friction stir system can be embodied as a closed loop tracking system, such as a robot-based tracked friction stir welding (FSW) or friction stir processing (FSP) system.

Four Principles for Selecting HCI Research Questions

DEFF Research Database (Denmark)

Clemmensen, Torkil

In this position paper, I present and explain the position that what we should study in HCI depends on the objective of the research and its political, social, cultural, technological, and historical context. I outline four principles for selecting research questions and give a personal account...... of how I have selected research questions using these four principles. The aim with the paper is to generate discussion and advance the understanding of what to study in HCI....

How e-government managers prioritise rival value positions

DEFF Research Database (Denmark)

Rose, J.; Persson, J. S.; Heeager, Lise Tordrup

2015-01-01

E-Government strategies, investments, project selection, and implementations are influenced by value positions deeply enshrined in the traditions of public administration, which are in turn reflected in the everyday discourse of public managers. We analyse value traditions in the public administr......E-Government strategies, investments, project selection, and implementations are influenced by value positions deeply enshrined in the traditions of public administration, which are in turn reflected in the everyday discourse of public managers. We analyse value traditions in the public...... of better services for citizens. Citizen engagement, with its roots in liberal democracy arguments, promotes responsiveness, consultation, collaboration and participation. A set of foundational values grounded in the deeply rooted bureaucratic tradition is also distinguished. A qualitative survey of Danish...... local authority managers’ value positions shows a heavy bias towards administrative efficiency and an absence of concern for citizen engagement. The implications of this efficiency imperative are discussed....

Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus

Science.gov (United States)

Tsujimura, Kunio; Takahashi, Toshitada; Morita, Akimichi; Hasegawa-Nishiwaki, Hitomi; Iwase, Shigeru; Obata, Yuichi

1996-01-01

the 14 clones. Taken together, these results suggest that Tlaa-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of γδ T cells. PMID:8976173

Age-related positivity enhancement is not universal: older Chinese look away from positive stimuli.

Science.gov (United States)

Fung, Helene H; Lu, Alice Y; Goren, Deborah; Isaacowitz, Derek M; Wadlinger, Heather A; Wilson, Hugh R

2008-06-01

Socioemotional selectivity theory postulates that with age, people are motivated to derive emotional meaning from life, leading them to pay more attention to positive relative to negative/neutral stimuli. The authors argue that cultures that differ in what they consider to be emotionally meaningful may show this preference to different extents. Using eye-tracking techniques, the authors compared visual attention toward emotional (happy, fearful, sad, and angry) and neutral facial expressions among 46 younger and 57 older Hong Kong Chinese. In contrast to prior Western findings, older but not younger Chinese looked away from happy facial expressions, suggesting that they do not show attentional preferences toward positive stimuli.

Religiousness, well-being and ageing – selected explanations of positive relationships

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Woźniak Barbara

2015-12-01

Full Text Available According to research that have been conducted in the field of gerontology, sociology and psychology of ageing, there is a relationship between the level of religious involvement and health status/ well-being/quality of life in older age. How does religiousness influence aging process and health status? The aim of the article is to review explanations of a positive relationship between religiousness and health that are discussed in the literature. Those explanations may be grouped in three broad categories reflecting three functions of religion that play a role for well-being in older age. Those functions are: (1 religiousness as a source of coherence and the role of religious coping and provision of meaning in dealing with stressful life events (including ageing losses (2 religiousness as a source of positive self-perception and a sense of personal control, (3 provision of social resources (i.e. social ties and social support within religious community and emphasis on interpersonal relations (with special focus on forgiveness as a norm in interpersonal relations. Those functions of religion are discussed in the context of their potential role in successful ageing, as determined by - among others - active engagement in life.

Navigation studies based on the ubiquitous positioning technologies

Science.gov (United States)

Ye, Lei; Mi, Weijie; Wang, Defeng

2007-11-01

This paper summarized the nowadays positioning technologies, such as absolute positioning methods and relative positioning methods, indoor positioning and outdoor positioning, active positioning and passive positioning. Global Navigation Satellite System (GNSS) technologies were introduced as the omnipresent out-door positioning technologies, including GPS, GLONASS, Galileo and BD-1/2. After analysis of the shortcomings of GNSS, indoor positioning technologies were discussed and compared, including A-GPS, Cellular network, Infrared, Electromagnetism, Computer Vision Cognition, Embedded Pressure Sensor, Ultrasonic, RFID (Radio Frequency IDentification), Bluetooth, WLAN etc.. Then the concept and characteristics of Ubiquitous Positioning was proposed. After the ubiquitous positioning technologies contrast and selection followed by system engineering methodology, a navigation system model based on Incorporate Indoor-Outdoor Positioning Solution was proposed. And this model was simulated in the Galileo Demonstration for World Expo Shanghai project. In the conclusion, the prospects of ubiquitous positioning based navigation were shown, especially to satisfy the public location information acquiring requirement.

A dye laser with a partial-selective resonator

Energy Technology Data Exchange (ETDEWEB)

Makogon, M M; Sukhanov, V B

1977-04-01

The possibility of controlling the width and spectral position of the generation line of an organic dye laser (Rhodamine 6Zh) whose resonator represents a combination of selective and non-selective channels is demonstrated. The selective channel entails an unsymmetrically mounted prism with whose angular displacement the spectral width can be changed within broad ranges; the non-selective channel maintains the resonator's quality at a sufficiently high level. An expression is given which makes it possible to determine the generation's spectral width when fixing the prism's angular position. The change in the rearrangement band was studied in relation to the qualities of the selective and non-selective channels as determined by the form of the active medium's amplification contour (a narrowing of the spectrum from 0.15 to 0.0019 nm led to a reduction of the rearrangement area from 38.4 to 28.3 nm).

Inference of purifying and positive selection in three subspecies of chimpanzees (Pan troglodytes) from exome sequencing

DEFF Research Database (Denmark)

Bataillon, Thomas; Duan, Jinjie; Hvilsom, Christina

2015-01-01

of recent gene flow from Western into Eastern chimpanzees. The striking contrast in X-linked vs. autosomal polymorphism and divergence previously reported in Central chimpanzees is also found in Eastern and Western chimpanzees. We show that the direction of selection (DoS) statistic exhibits a strong non......-monotonic relationship with the strength of purifying selection S, making it inappropriate for estimating S. We instead use counts in synonymous vs. non-synonymous frequency classes to infer the distribution of S coefficients acting on non-synonymous mutations in each subspecies. The strength of purifying selection we...... infer is congruent with the differences in effective sizes of each subspecies: Central chimpanzees are undergoing the strongest purifying selection followed by Eastern and Western chimpanzees. Coding indels show stronger selection against indels changing the reading frame than observed in human...

The Evaluation and Selection of a Fifth Ground Antenna Site for the Global Positioning System.

Science.gov (United States)

1987-12-07

selection was the region between Australia and South America and north of the Antartic . Using the performance results of this study, further study...indicated that the best region for selection was between Australia and South America and north of the Antartic . Using the performance results of this

Destabilized and catalyzed borohydride for reversible hydrogen storage

Science.gov (United States)

Mohtadi, Rana F [Northville, MI; Nakamura, Kenji [Toyota, JP; Au, Ming [Martinez, GA; Zidan, Ragaiy [Alken, SC

2012-01-31

A process of forming a hydrogen storage material, including the steps of: providing a first material of the formula M(BH.sub.4).sub.X, where M is an alkali metal or an alkali earth metal, providing a second material selected from M(AlH.sub.4).sub.x, a mixture of M(AlH.sub.4).sub.x and MCl.sub.x, a mixture of MCl.sub.x and Al, a mixture of MCl.sub.x and AlH.sub.3, a mixture of MH.sub.x and Al, Al, and AlH.sub.3. The first and second materials are combined at an elevated temperature and at an elevated hydrogen pressure for a time period forming a third material having a lower hydrogen release temperature than the first material and a higher hydrogen gravimetric density than the second material.

Substitution rate and natural selection in parvovirus B19

Science.gov (United States)

Stamenković, Gorana G.; Ćirković, Valentina S.; Šiljić, Marina M.; Blagojević, Jelena V.; Knežević, Aleksandra M.; Joksić, Ivana D.; Stanojević, Maja P.

2016-01-01

The aim of this study was to estimate substitution rate and imprints of natural selection on parvovirus B19 genotype 1. Studied datasets included 137 near complete coding B19 genomes (positions 665 to 4851) for phylogenetic and substitution rate analysis and 146 and 214 partial genomes for selection analyses in open reading frames ORF1 and ORF2, respectively, collected 1973–2012 and including 9 newly sequenced isolates from Serbia. Phylogenetic clustering assigned majority of studied isolates to G1A. Nucleotide substitution rate for total coding DNA was 1.03 (0.6–1.27) x 10−4 substitutions/site/year, with higher values for analyzed genome partitions. In spite of the highest evolutionary rate, VP2 codons were found to be under purifying selection with rare episodic positive selection, whereas codons under diversifying selection were found in the unique part of VP1, known to contain B19 immune epitopes important in persistent infection. Analyses of overlapping gene regions identified nucleotide positions under opposite selective pressure in different ORFs, suggesting complex evolutionary mechanisms of nucleotide changes in B19 viral genomes. PMID:27775080

Toddlers Selectively Help Fair Agents

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Luca Surian

2017-06-01

Full Text Available Previous research showed that infants and toddlers are inclined to help prosocial agents and assign a positive valence to fair distributions. Also, they expect that positive and negative actions directed toward distributors will conform to reciprocity principles. This study investigates whether toddlers are selective in helping others, as a function of others’ previous distributive actions. Toddlers were presented with real-life events in which two actresses distributed resources either equally or unequally between two puppets. Then, they played together with a ball that accidentally fell to the ground and asked participants to help them to retrieve it. Participants preferred to help the actress who performed equal distributions. This finding suggests that by the second year children’s prosocial actions are modulated by their emerging sense of fairness.HighlightsToddlers (mean age = 25 months are selective in helping distributors.Toddlers prefer helping a fair rather than an unfair distributor.Toddlers’ selective helping provides evidence for an early sense of fairness.

Lateral decubitus position vs. lithotomy position: which is the best way to minimize patient’s pain perception during transrectal prostate biopsy?

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Phil Hyun Song

Full Text Available ABSTRACT Introduction Considering the distinctive nature in terms of psychological stress and anal tone of position which is generally selected between lithotomy and left lateral decubitus (LLD, we postulated its effect on pain perception during biopsy, and investigated their association. Materials and Methods A prospective study for comparison of two biopsy positions which were perform in a different working day was conducted for 208 men (lithotomy position=86, LLD=122. The decision on the position was made solely based on the patient’s preference for the biopsy day, and all procedures were performed according to the identical protocol (12-core biopsy with intrarectal lidocaine gel, probe, and needle. The maximal degree of pain during the entire process was assessed using a visual analogue scale (VAS, immediately after biopsy. After propensity matching, a total of 152 patients were finally selected (lithotomy group=76, LLD=76, then peri-biopsy parameters were compared. Results Between groups, no differences were observed across all variables including age, obesity, prostate volume, serum PSA, international prostate symptom score, and cancer detection rate, except mean (±standard deviation VAS score (3.89±2.01 vs. 4.58±2.22, p=0.049. VAS score showed significant association solely with patient’s position (Pearson’s coefficient=-0.165, p=0.042. In multiple linear regression models regarding the effect of clinical variables on VAS score, patient position was a single independent predictor favoring lithotomy position to decrease perceived pain (B=-0.928, p=0.024. Conclusions These data suggest lithotomy position as a proper way to perform transrectal prostate biopsy with routine use of topical lidocaine gel in comparison with conventional LLD position.

Selective mutism.

Science.gov (United States)

Hua, Alexandra; Major, Nili

2016-02-01

Selective mutism is a disorder in which an individual fails to speak in certain social situations though speaks normally in other settings. Most commonly, this disorder initially manifests when children fail to speak in school. Selective mutism results in significant social and academic impairment in those affected by it. This review will summarize the current understanding of selective mutism with regard to diagnosis, epidemiology, cause, prognosis, and treatment. Studies over the past 20 years have consistently demonstrated a strong relationship between selective mutism and anxiety, most notably social phobia. These findings have led to the recent reclassification of selective mutism as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. In addition to anxiety, several other factors have been implicated in the development of selective mutism, including communication delays and immigration/bilingualism, adding to the complexity of the disorder. In the past few years, several randomized studies have supported the efficacy of psychosocial interventions based on a graduated exposure to situations requiring verbal communication. Less data are available regarding the use of pharmacologic treatment, though there are some studies that suggest a potential benefit. Selective mutism is a disorder that typically emerges in early childhood and is currently conceptualized as an anxiety disorder. The development of selective mutism appears to result from the interplay of a variety of genetic, temperamental, environmental, and developmental factors. Although little has been published about selective mutism in the general pediatric literature, pediatric clinicians are in a position to play an important role in the early diagnosis and treatment of this debilitating condition.

Selective versus non-selective culture medium for group B streptococcus detection in pregnancies complicated by preterm labor or preterm-premature rupture of membranes

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Marcelo Luís Nomura

Full Text Available The objective of this study was to identify group B streptococcus (GBS colonization rates and compare detection efficiency of selective versus non-selective culture media and anorectal versus vaginal cultures in women with preterm labor and preterm-premature rupture of membranes (PROM. A prospective cohort study of 203 women was performed. Two vaginal and two anorectal samples from each woman were collected using sterile swabs. Two swabs (one anorectal and one vaginal were placed separately in Stuart transport media and cultured in blood-agar plates for 48 hours; the other two swabs were inoculated separately in Todd-Hewitt selective media for 24 hours and then subcultured in blood-agar plates. Final GBS identification was made by the CAMP test. A hundred thrity-two cultures out of 812 were positive. The maternal colonization rate was 27.6%. Colonization rates were 30% for preterm PROM and 25.2% for preterm labor. Todd-Hewitt selective medium detected 87.5% and non-selective medium 60.7% GBS-positive women. Vaginal samples and anorectal samples had the same detection rate of 80.3%. Anorectal selective cultures detected 75% of carriers; 39% of GBS-positive women were detected only in selective medium. A combined vaginal-anorectal selective culture is appropriate for GBS screening in this population, minimizing laboratory costs.

Differential selection on carotenoid biosynthesis genes as a function of gene position in the metabolic pathway: a study on the carrot and dicots.

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Jérémy Clotault

Full Text Available Selection of genes involved in metabolic pathways could target them differently depending on the position of genes in the pathway and on their role in controlling metabolic fluxes. This hypothesis was tested in the carotenoid biosynthesis pathway using population genetics and phylogenetics.Evolutionary rates of seven genes distributed along the carotenoid biosynthesis pathway, IPI, PDS, CRTISO, LCYB, LCYE, CHXE and ZEP, were compared in seven dicot taxa. A survey of deviations from neutrality expectations at these genes was also undertaken in cultivated carrot (Daucus carota subsp. sativus, a species that has been intensely bred for carotenoid pattern diversification in its root during its cultivation history. Parts of sequences of these genes were obtained from 46 individuals representing a wide diversity of cultivated carrots. Downstream genes exhibited higher deviations from neutral expectations than upstream genes. Comparisons of synonymous and nonsynonymous substitution rates between genes among dicots revealed greater constraints on upstream genes than on downstream genes. An excess of intermediate frequency polymorphisms, high nucleotide diversity and/or high differentiation of CRTISO, LCYB1 and LCYE in cultivated carrot suggest that balancing selection may have targeted genes acting centrally in the pathway.Our results are consistent with relaxed constraints on downstream genes and selection targeting the central enzymes of the carotenoid biosynthesis pathway during carrot breeding history.

Modeling HIV-1 drug resistance as episodic directional selection.

Science.gov (United States)

Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad

2012-01-01

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

Modeling HIV-1 drug resistance as episodic directional selection.

Directory of Open Access Journals (Sweden)

Ben Murrell

Full Text Available The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

Activities for Teaching Positive Psychology: A Guide for Instructors

Science.gov (United States)

Froh, Jeffrey J., Ed.; Parks, Acacia C., Ed.

2012-01-01

Positive psychology is a rapidly expanding area of study that is of great interest to students at the graduate, undergraduate, and high school levels. But the field is so broad that teachers who want to cover all the bases when designing a positive psychology course may have difficulty locating and selecting materials. "Activities for Teaching…

Destabilization emulsion of oil by means of additives based on silicones polyethers; Desestabilizacao de emulsoes de petroleo por meio de aditivos a base de silicones polieteres

Energy Technology Data Exchange (ETDEWEB)

Jarque, Erika A.; Mansur, Claudia R.E. [Universidade Federal do Rio de Janeiro (IMA/UFRJ), RJ (Brazil). Inst. de Macromoleculas Professora Eloisa Mano], e-mails: alegrio@ima.ufrj.br, celias@ima.ufrj.br

2011-07-01

The process of demulsification has great importance in the petroleum industry, since the formation of emulsions is a natural phenomenon in this sector. Several polymers have been used commercially as additives emulsion destabilizing, among them are the block copolymers of poly (ethylene oxide)-poly (propylene oxide) (PEO-PPO). This work aims to study the efficiency of five additives based on silicones polyethers, which have structures in their chains of poly (ethylene oxide) (PEO) or PEO-PPO copolymers. The results show that the addition of these additives in the water / oil reduced the values of interfacial tension of systems. From the testing of gravitational separation water / oil was observed that all the additives promoted the breakdown of water / oil, but those who hold in their structures the chains of block copolymers of PEO-PPO were the most efficient, and that the caused a smaller reduction in the interfacial tensions of these systems. (author)

Exposure to selected fragrance materials. A case study of fragrance-mix-positive eczema patients

DEFF Research Database (Denmark)

Johansen, J D; Rastogi, Suresh Chandra; Menné, T

1996-01-01

. In all cases, the use of these cosmetics completely or partly explained present or past episodes of eczema. Between 1 to 6 constituents of the fragrance mix were found in 22 out of 23 products. The cosmetics of all the patients sensitive to hydroxycitronellal, eugenol, cinnamic alcohol and alpha......The aim of the present study was to assess exposure to constituents of the fragrance mix from cosmetic products used by fragrance-mix-positive eczema patients. 23 products, which had either given a positive patch and/or use test in a total of 11 fragrance-mix-positive patients, were analyzed....... It is concluded that exposure to constituents of the fragrance mix is common in fragrance-allergic patients with cosmetic eczema, and that the fragrance mix is a good reflection of actual exposure....

Selfing ability and dispersal are positively related, but not affected by range position: a multispecies study on southern African Asteraceae.

Science.gov (United States)

de Waal, C; Rodger, J G; Anderson, B; Ellis, A G

2014-05-01

Dispersal and breeding system traits are thought to affect colonization success. As species have attained their present distribution ranges through colonization, these traits may vary geographically. Although several theories predict associations between dispersal ability, selfing ability and the relative position of a population within its geographic range, there is little theoretical or empirical consensus on exactly how these three variables are related. We investigated relationships between dispersal ability, selfing ability and range position across 28 populations of 13 annual, wind-dispersed Asteraceae species from the Namaqualand region of South Africa. Controlling for phylogeny, relative dispersal ability--assessed from vertical fall time of fruits--was positively related to an index of autofertility--determined from hand-pollination experiments. These findings support the existence of two discrete syndromes: high selfing ability associated with good dispersal and obligate outcrossing associated with lower dispersal ability. This is consistent with the hypothesis that selection for colonization success drives the evolution of an association between these traits. However, no general effect of range position on dispersal or breeding system traits was evident. This suggests selection on both breeding system and dispersal traits acts consistently across distribution ranges. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Finding Direction in the Search for Selection

OpenAIRE

Thiltgen, G.; Dos Reis, M.; Goldstein, R. A.

2016-01-01

Tests for positive selection have mostly been developed to look for diversifying selection where change away from the current amino acid is often favorable. However, in many cases we are interested in directional selection where there is a shift toward specific amino acids, resulting in increased fitness in the species. Recently, a few methods have been developed to detect and characterize directional selection on a molecular level. Using the results of evolutionary simulations as well as HIV...

Women Aspiring to Administrative Positions in Kenya Municipal Primary Schools

Science.gov (United States)

Combat, Victor F. O.

2014-01-01

Even though female teachers in Kenya municipal primary schools are majority and highly qualified, they fill fewer administrative positions than men. This study assesses the extent of women's participation in leadership positions, society's perception of female leaders, selection criteria of educational administrators, and barriers that affect or…

Patient positioning and ventilator-associated pneumonia.

Science.gov (United States)

Hess, Dean R

2005-07-01

Rotational beds, prone position, and semi-recumbent position have been proposed as procedures to prevent ventilator-associated pneumonia (VAP). Rotational therapy uses a special bed designed to turn continuously, or nearly continuously, the patient from side to side; specific designs include kinetic therapy and continuous lateral rotation therapy. A meta-analysis of studies evaluating the effect of rotational bed therapy shows a decrease in the risk of pneumonia but no effect on mortality. Two studies reported a lower risk of VAP in patients placed in a prone position, with no effect on mortality. Studies using radiolabeled enteral feeding solutions in mechanically ventilated patients have reported that aspiration of gastric contents occurs to a greater degree when patients are in the supine position, compared with the semirecumbent position. One study reported a lower rate of VAP in patients randomized to semi-recumbent compared to supine position. Although each of the techniques discussed in this paper has been shown to reduce the risk of VAP, none has been shown to affect mortality. The available evidence suggests that semi-recumbent position should be used routinely, rotational therapy should be considered in selected patients, and prone position should not be used as a technique to reduce the risk of VAP.

Three-dimensional, position-sensitive radiation detection

Science.gov (United States)

He, Zhong; Zhang, Feng

2010-04-06

Disclosed herein is a method of determining a characteristic of radiation detected by a radiation detector via a multiple-pixel event having a plurality of radiation interactions. The method includes determining a cathode-to-anode signal ratio for a selected interaction of the plurality of radiation interactions based on electron drift time data for the selected interaction, and determining the radiation characteristic for the multiple-pixel event based on both the cathode-to-anode signal ratio and the electron drift time data. In some embodiments, the method further includes determining a correction factor for the radiation characteristic based on an interaction depth of the plurality of radiation interactions, a lateral distance between the selected interaction and a further interaction of the plurality of radiation interactions, and the lateral positioning of the plurality of radiation interactions.

Dependence of radar auroral scattering cross section on the ambient electron density and the destabilizing electric field

International Nuclear Information System (INIS)

Haldoupis, C.; Nielsen, E.; Schlegel, K.

1990-01-01

By using a data set that includes simultaneous STARE and EISCAT measurements made at a common magnetic flux tube E region in the ionosphere, we investigate the dependence of relative scattering cross section of 1-meter auroral irregularities on the destabilizing E x B electron drift, or alternatively the electric field, and the E region ambient electron density. The analysis showed that both, the E field and mean electron density are the decisive factors in determining the strength of radar auroral echoes at magnetic aspect angles near perpendicularity. We have found that at instability threshold, i.e., when the E field strength is in the 15 to 20 mV/m range, the backscatter power level is affected strongly by the mean electron density. Above threshold, the wave saturation amplitudes are determined mainly by the combined action of electron drift velocity magnitude, V d , and mean electron density, N e , in a way that the scattering cross section, or the electron density fluctuation level, increases with electric field magnitude but at a rate which is larger when the ambient electron density is lower. The analysis enabled us to infer an empirical functional relationship which is capable of predicting reasonably well the intensity of STARE echoes from EISCAT E field and electron density data. In this functional relationship, the received power at threshold depends on N e 2 whereas, from threshold to perhaps more than 50 mV/m, the power increases nonlinearly with drift velocity as V d n where the exponent n is approximately proportional to N e -1/2 . The results support the Farley-Bunemann instability as the primary instability mechanism, but the existing nonlinear treatment of the theory, which includes wave-induced cross field diffusion, cannot account for the observed role of electron density in the saturation of irregularity amplitudes

Sexual selection and allometry: a critical reappraisal of the evidence and ideas.

Science.gov (United States)

Bonduriansky, Russell

2007-04-01

One of the most pervasive ideas in the sexual selection literature is the belief that sexually selected traits almost universally exhibit positive static allometries (i.e., within a sample of conspecific adults, larger individuals have disproportionally larger traits). In this review, I show that this idea is contradicted by empirical evidence and theory. Although positive allometry is a typical attribute of some sexual traits in certain groups, the preponderance of positively allometric sexual traits in the empirical literature apparently results from a sampling bias reflecting a fascination with unusually exaggerated (bizarre) traits. I review empirical examples from a broad range of taxa illustrating the diversity of allometric patterns exhibited by signal, weapon, clasping and genital traits, as well as nonsexual traits. This evidence suggests that positive allometry may be the exception rather than the rule in sexual traits, that directional sexual selection does not necessarily lead to the evolution of positive allometry and, conversely, that positive allometry is not necessarily a consequence of sexual selection, and that many sexual traits exhibit sex differences in allometric intercept rather than slope. Such diversity in the allometries of secondary sexual traits is to be expected, given that optimal allometry should reflect resource allocation trade-offs, and patterns of sexual and viability selection on both trait size and body size. An unbiased empirical assessment of the relation between sexual selection and allometry is an essential step towards an understanding of this diversity.

EDITORIAL: Nanotechnological selection Nanotechnological selection

Science.gov (United States)

Demming, Anna

2013-01-01

At the nanoscale measures can move from a mass-scale analogue calibration to counters of discrete units. The shift redefines the possible levels of control that can be achieved in a system if adequate selectivity can be imposed. As an example as ionic substances pass through nanoscale pores, the quantity of ions is low enough that the pore can contain either negative or positive ions. Yet precise control over this selectivity still raises difficulties. In this issue researchers address the challenge of how to regulate the ionic selectivity of negative and positive charges with the use of an external charge. The approach may be useful for controlling the behaviour, properties and chemical composition of liquids and has possible technical applications for nanofluidic field effect transistors [1]. Selectivity is a critical advantage in the administration of drugs. Nanoparticles functionalized with targeting moieties can allow delivery of anti-cancer drugs to tumour cells, whilst avoiding healthy cells and hence reducing some of the debilitating side effects of cancer treatments [2]. Researchers in Belarus and the US developed a new theranostic approach—combining therapy and diagnosis—to support the evident benefits of cellular selectivity that can be achieved when nanoparticles are applied in medicine [3]. Their process uses nanobubbles of photothermal vapour, referred to as plasmonic nanobubbles, generated by plasmonic excitations in gold nanoparticles conjugated to diagnosis-specific antibodies. The intracellular plasmonic nanobubbles are controlled by laser fluence so that the response can be tuned in individual living cells. Lower fluence allows non-invasive high-sensitive imaging for diagnosis and higher fluence can disrupt the cellular membrane for treatments. The selective response of carbon nanotubes to different gases has leant them to be used within various different types of sensors, as summarized in a review by researchers at the University of

Interaction of elaiophylin with model bilayer membrane

Science.gov (United States)

Genova, J.; Dencheva-Zarkova, M.

2017-01-01

Elaiophylin is a new macrodiolide antibiotic, which is produced by the Streptomyces strains [1]. It displays biological activities against Gram-positive bacteria and fungi. The mode of action of this antibiotic has been attributed to an alteration of the membrane permeability. When this antibiotic is inserted into the bilayer membranes destabilization of the membrane and formation of ion-penetrable channels is observed. The macrodiolide antibiotic forms stable cation selective ion channels in synthetic lipid bilayer membranes. The aim of this work was to study the interactions of Elaiophylin with model bilayer membranes and to get information on the mechanical properties of lipid bilayers in presence of this antibiotic. Patch-clamp technique [2] were used in the study

Evolution of genetic architecture under directional selection.

Science.gov (United States)

Hansen, Thomas F; Alvarez-Castro, José M; Carter, Ashley J R; Hermisson, Joachim; Wagner, Günter P

2006-08-01

We investigate the multilinear epistatic model under mutation-limited directional selection. We confirm previous results that only directional epistasis, in which genes on average reinforce or diminish each other's effects, contribute to the initial evolution of mutational effects. Thus, either canalization or decanalization can occur under directional selection, depending on whether positive or negative epistasis is prevalent. We then focus on the evolution of the epistatic coefficients themselves. In the absence of higher-order epistasis, positive pairwise epistasis will tend to weaken relative to additive effects, while negative pairwise epistasis will tend to become strengthened. Positive third-order epistasis will counteract these effects, while negative third-order epistasis will reinforce them. More generally, gene interactions of all orders have an inherent tendency for negative changes under directional selection, which can only be modified by higher-order directional epistasis. We identify three types of nonadditive quasi-equilibrium architectures that, although not strictly stable, can be maintained for an extended time: (1) nondirectional epistatic architectures; (2) canalized architectures with strong epistasis; and (3) near-additive architectures in which additive effects keep increasing relative to epistasis.

Sport Management Interns--Selection Qualifications.

Science.gov (United States)

Cuneen, Jacquelyn; Sidwell, M. Joy

1993-01-01

Examines and rates the background qualifications and qualities, identified by sport management practitioners through an examination of paper credentials, that are desired in interviewees vying for selection into sport management internship positions. (GLR)

Rejection Positivity Predicts Trial-to-Trial Reaction Times in an Auditory Selective Attention Task: A Computational Analysis of Inhibitory Control

Directory of Open Access Journals (Sweden)

Sufen eChen

2014-08-01

Full Text Available A series of computer simulations using variants of a formal model of attention (Melara & Algom, 2003 probed the role of rejection positivity (RP, a slow-wave electroencephalographic (EEG component, in the inhibitory control of distraction. Behavioral and EEG data were recorded as participants performed auditory selective attention tasks. Simulations that modulated processes of distractor inhibition accounted well for reaction-time (RT performance, whereas those that modulated target excitation did not. A model that incorporated RP from actual EEG recordings in estimating distractor inhibition was superior in predicting changes in RT as a function of distractor salience across conditions. A model that additionally incorporated momentary fluctuations in EEG as the source of trial-to-trial variation in performance precisely predicted individual RTs within each condition. The results lend support to the linking proposition that RP controls the speed of responding to targets through the inhibitory control of distractors.

The role of the C-domain of bacteriophage T4 gene 32 protein in ssDNA binding and dsDNA helix-destabilization: Kinetic, single-molecule, and cross-linking studies

Science.gov (United States)

Pant, Kiran; Anderson, Brian; Perdana, Hendrik; Malinowski, Matthew A.; Win, Aye T.; Williams, Mark C.

2018-01-01

The model single-stranded DNA binding protein of bacteriophage T4, gene 32 protein (gp32) has well-established roles in DNA replication, recombination, and repair. gp32 is a single-chain polypeptide consisting of three domains. Based on thermodynamics and kinetics measurements, we have proposed that gp32 can undergo a conformational change where the acidic C-terminal domain binds internally to or near the single-stranded (ss) DNA binding surface in the core (central) domain, blocking ssDNA interaction. To test this model, we have employed a variety of experimental approaches and gp32 variants to characterize this conformational change. Utilizing stopped-flow methods, the association kinetics of wild type and truncated forms of gp32 with ssDNA were measured. When the C-domain is present, the log-log plot of k vs. [NaCl] shows a positive slope, whereas when it is absent (*I protein), there is little rate change with salt concentration, as expected for this model.A gp32 variant lacking residues 292–296 within the C-domain, ΔPR201, displays kinetic properties intermediate between gp32 and *I. The single molecule force-induced DNA helix-destabilizing activitiesas well as the single- and double-stranded DNA affinities of ΔPR201 and gp32 truncated at residue 295 also fall between full-length protein and *I. Finally, chemical cross-linking of recombinant C-domain and gp32 lacking both N- and C-terminal domains is inhibited by increasing concentrations of a short single-stranded oligonucleotide, and the salt dependence of cross-linking mirrors that expected for the model. Taken together, these results provide the first evidence in support of this model that have been obtained through structural probes. PMID:29634784

Discriminant analysis of maintaining a vertical position in the water

Directory of Open Access Journals (Sweden)

Bratuša Zoran

2015-01-01

Full Text Available Water polo is the only sports game that takes place in the water. During the outplay, a vertical body position with the two basic mechanisms of the leg work - a breaststroke leg kick and an eggbeater leg kick, prevails. Starting from the significance of a vertical position during the game play, the methods of assessing physical preparedness of the athletes of all the categories also include the evaluation of maintaining a vertical position and consequently the load of the leg muscles. The measurements are performed during the maintenance of a vertical position (swimming in place through one of the specified mechanisms of leg work, i.e. a vertical position technique. The aim of this paper was to determine the application of different mechanisms of the leg kicks in maintaining a vertical position with young water polo players in relation to their position. The study included 29 selected junior water polo players (age_15.8 ± 0.8 years; BH_185.2 ± 5.3cm and BW_81.7 ± 7.7kg. The measurements were performed during the tests of swimming in place at the maximum intensity lasting 10 seconds, by the breaststroke and eggbeater leg kicks. The isometric tensiometry tests were used for the measurements. The results were analysed by the application of descriptive statistics, and the kinetic selection characteristic was defined by the application of discriminant analysis. Higher average values were achieved with the breaststroke leg kick technique Fmax, ImpF and RFD (avgFmaxLEGGBK =157.46±19.93N; avgImpF_LEGGBK =45.43±10.64Ns; avgRFD_LEGGBK=337.85±80.73N/s; avgFmaxLBKICK=227.18±49.17N; avgImpF_LBKICK=55.99±14.59Ns; avgRFD_LBKICK=545.47±159.15N/s. After discriminant analysis, the results have shown that the eggbeater leg kick is a selection technique, whereas the force - Fmax is a kinetic selection variable. Based on the obtained results and the analyses performed it may be concluded that a training factor dominant for maintaining a vertical position by

Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure

Energy Technology Data Exchange (ETDEWEB)

Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu

2016-03-15

The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.

Fishing destabilizes the biomass flow in the marine size spectrum

OpenAIRE

Rochet, M.-J.; Benoît, E.

2011-01-01

Fishing impacts on marine food webs are predicted by simulations of a size spectrum community model. In this model, predation is determined by predator and prey size and abundance, and drives predator growth and prey mortality. Fishing amplifies temporal oscillations in the biomass flow. Oscillations appear at lower fishing intensity and have wider amplitude when fishing is selective (removes a narrow size range) and/or when large fish are targeted, than when fishing is more balanced (catchin...

Detection of shielded radionuclides from weak and poorly resolved spectra using group positive RIVAL

International Nuclear Information System (INIS)

Kump, Paul; Bai, Er-Wei; Chan, Kung-Sik; Eichinger, William

2013-01-01

This paper is concerned with the identification of nuclides from weak and poorly resolved spectra in the presence of unknown radiation shielding materials such as carbon, water, concrete and lead. Since a shield will attenuate lower energies more so than higher ones, isotope sub-spectra must be introduced into models and into detection algorithms. We propose a new algorithm for detection, called group positive RIVAL, that encourages the selection of groups of sub-spectra rather than the selection of individual sub-spectra that may be from the same parent isotope. Indeed, the proposed algorithm incorporates group positive LASSO, and, as such, we supply the consistency results of group positive LASSO and adaptive group positive LASSO. In an example employing various shielding materials and material thicknesses, group positive RIVAL is shown to perform well in all scenarios with the exception of ones in which the shielding material is lead. - Highlights: ► Identification of nuclides from weak and poorly resolved spectra. ► Shielding materials such as carbon, water, concrete, and lead are considered. ► Isotope spectra are decomposed into their sub-spectra. ► A variable selection algorithm is proposed that encourages group selection. ► Simulations demonstrate the proposed method's performance when nuclides have been shielded

Selection Demands and Working Memory Mediate Interference during Naming

Directory of Open Access Journals (Sweden)

Julie W Hughes

2015-05-01

Analyzing RTs, we replicated previous SI effects in BCN in healthy subjects and patients (reported effects’ p’s < .05. Subjects responded more slowly to items in semantically related vs. unrelated groups, and this interference increased across cycles (evidence of increasing selection demands; Figures 1a/c. Indicative of WM, healthy subjects were faster to name items as the number of unrelated items to be named (i.e., remembered decreased. However, this was attenuated by selection demand, as there was no decrease in RTs across repeated related items (Figure 1b. Converging evidence from patients demonstrated more impaired selection capacity produced increasingly slower RTs across item positions within the related condition (high selection demand (Figure 1d. Larger WM capacity (rhyme probe but not category probe, p = .54 produced increasingly faster RTs across items positions in the unrelated condition (low selection demand (Figure 1e. Together, these findings suggest that both selection demand and phonological WM processes mediate interference during naming.

Positive psychiatry: its time has come.

Science.gov (United States)

Jeste, Dilip V; Palmer, Barton W; Rettew, David C; Boardman, Samantha

2015-06-01

Traditionally, psychiatry has been defined and practiced as a branch of medicine focused on the diagnosis and treatment of mental illnesses. Based on growing empirical evidence, we believe that this definition warrants expansion to include the concept of positive psychiatry. In the present article, we provide a critical overview of this emerging field and a select review of relevant scientific literature. Positive psychiatry may be defined as the science and practice of psychiatry that seeks to understand and promote well-being through assessment and interventions involving positive psychosocial characteristics (PPCs) in people who suffer from or are at high risk of developing mental or physical illnesses. It can also benefit nonclinical populations. Positive psychiatry has 4 main components: (1) positive mental health outcomes (eg, well-being), (2) PPCs that comprise psychological traits (resilience, optimism, personal mastery and coping self-efficacy, social engagement, spirituality and religiosity, and wisdom-including compassion) and environmental factors (family dynamics, social support, and other environmental determinants of overall health), (3) biology of positive psychiatry constructs, and (4) positive psychiatry interventions including preventive ones. There are promising empirical data to suggest that positive traits may be improved through psychosocial and biological interventions. As a branch of medicine rooted in biology, psychiatry, especially with the proposed conceptualization of positive psychiatry, is well poised to provide major contributions to the positive mental health movement, thereby impacting the overall health care of the population. © Copyright 2015 Physicians Postgraduate Press, Inc.

Positive Psychiatry: Its Time Has Come

Science.gov (United States)

Jeste, Dilip V.; Palmer, Barton W.; Rettew, David C.; Boardman, Samantha

2017-01-01

Traditionally, psychiatry has been defined and practiced as a branch of medicine focused on the diagnosis and treatment of mental illnesses. Based on growing empirical evidence, we believe that this definition warrants expansion to include the concept of positive psychiatry. In the present article we provide a critical overview of this emerging field and a select review of relevant scientific literature. Positive psychiatry may be defined as the science and practice of psychiatry that seeks to understand and promote well-being through assessment and interventions involving positive psychosocial characteristics (PPCs) in people who suffer from or are at high risk of developing mental or physical illnesses. It can also benefit non-clinical populations. Positive psychiatry has 4 main components: (1) positive mental health outcomes (e.g., well-being), (2) PPCs that comprise psychological traits (resilience, optimism, personal mastery and coping self-efficacy, social engagement, spirituality and religiosity, and wisdom - including compassion) and environmental factors (family dynamics, social support, and other environmental determinants of overall health), (3) biology of positive psychiatry constructs, and (4) positive psychiatry Interventions including preventive ones. There are promising empirical data to suggest that positive traits may be improved through psychosocial and biological interventions. As a branch of medicine, rooted in biology, psychiatry, especially with the proposed conceptualization of positive psychiatry, is well poised to provide major contributions to the positive mental health movement, thereby impacting the overall healthcare of the population. PMID:26132670

ROMANIAN BUSINESS POSITION ON THE CONTEMPORARY GLOBALIZATION CHESSBOARD

Directory of Open Access Journals (Sweden)

Aurica Grec

2012-01-01

Full Text Available Given that from the global hat appear, one by one, new dangers, threats and risks which are destabilizing market forces, nowadays we’re seeing a pattern with non-predictable EFS (economic, financial, social indicators. In this context, appear new paradoxes, so as the states desired to achieve a better and more sustainable networking, they found that such reaction generate, on the domino principle, other countries security. We refer here both to the military and security side and to the non military one, in order to underline the dimensions of the LRI (local, regional, international scenarios. They are becoming more complicated and also are fighting with lack of vision for to identify, in real time, the ways to counter the micro-macro effects on the current organizational level.

Visuospatial selective attention in chickens.

Science.gov (United States)

Sridharan, Devarajan; Ramamurthy, Deepa L; Schwarz, Jason S; Knudsen, Eric I

2014-05-13

Voluntary control of attention promotes intelligent, adaptive behaviors by enabling the selective processing of information that is most relevant for making decisions. Despite extensive research on attention in primates, the capacity for selective attention in nonprimate species has never been quantified. Here we demonstrate selective attention in chickens by applying protocols that have been used to characterize visual spatial attention in primates. Chickens were trained to localize and report the vertical position of a target in the presence of task-relevant distracters. A spatial cue, the location of which varied across individual trials, indicated the horizontal, but not vertical, position of the upcoming target. Spatial cueing improved localization performance: accuracy (d') increased and reaction times decreased in a space-specific manner. Distracters severely impaired perceptual performance, and this impairment was greatly reduced by spatial cueing. Signal detection analysis with an "indecision" model demonstrated that spatial cueing significantly increased choice certainty in localizing targets. By contrast, error-aversion certainty (certainty of not making an error) remained essentially constant across cueing protocols, target contrasts, and individuals. The results show that chickens shift spatial attention rapidly and dynamically, following principles of stimulus selection that closely parallel those documented in primates. The findings suggest that the mechanisms that control attention have been conserved through evolution, and establish chickens--a highly visual species that is easily trained and amenable to cutting-edge experimental technologies--as an attractive model for linking behavior to neural mechanisms of selective attention.

Selection of permanent pacing position of cardiac ventricle in patients with complete right bundle branch block

International Nuclear Information System (INIS)

Yang Minquan; Zhou Jun; Zhu Yan; Wang Jin; Rong Xin; Zhang Xiaoyi

2005-01-01

Objective: To find out the optimal pacing localization by comparing different pacing positions of the right ventricle in brady-cardiacarrhythmia patients with complete right bundle branch block. Methods: DDD type of double lumen permanent pacemaker was implanted in each of the 8 cases of sick sinus syndrome (SSS) and/or III degree atrioventricular block (III degree AVB) with complete right bundle branch block in normal heart function or class I. For each patient, four pacing positions in right ventricle were compared and the QRS pacing durations were recorded. The position with the shortest the QRS duration was chosen as the permanent pacing position. Heart function, chest X-rays and left ventricle ejection fraction (LVEF) were followed up after the operation. Results: In all the 8 cases, the posterior septum of the right ventricle were chosen as the permanent pacing position, with the shorter pacing QRS duration than that of pre-operation (P<0.05) and other pacing positions of the right ventricle. All parameters of this permanent pacing position were within the normal range. During the follow-up of 6-36 months, no abnormity was found in cardiac functions. Conclusion: In brady-cardiacarrhythmia patients with complete right bundle branch block, the implantation of permanent pacemaker should be at the junction region of inlet and outlet tracts, of the posterior septum of the right ventricle with ideal physiological function. (authors)

Selective Preference of Parallel DNA Triplexes Is Due to the Disruption of Hoogsteen Hydrogen Bonds Caused by the Severe Nonisostericity between the G*GC and T*AT Triplets.

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Gunaseelan Goldsmith

Full Text Available Implications of DNA, RNA and RNA.DNA hybrid triplexes in diverse biological functions, diseases and therapeutic applications call for a thorough understanding of their structure-function relationships. Despite exhaustive studies mechanistic rationale for the discriminatory preference of parallel DNA triplexes with G*GC & T*AT triplets still remains elusive. Here, we show that the highest nonisostericity between the G*GC & T*AT triplets imposes extensive stereochemical rearrangements contributing to context dependent triplex destabilisation through selective disruption of Hoogsteen scheme of hydrogen bonds. MD simulations of nineteen DNA triplexes with an assortment of sequence milieu reveal for the first time fresh insights into the nature and extent of destabilization from a single (non-overlapping, double (overlapping and multiple pairs of nonisosteric base triplets (NIBTs. It is found that a solitary pair of NIBTs, feasible either at a G*GC/T*AT or T*AT/G*GC triplex junction, does not impinge significantly on triplex stability. But two overlapping pairs of NIBTs resulting from either a T*AT or a G*GC interruption disrupt Hoogsteen pair to a noncanonical mismatch destabilizing the triplex by ~10 to 14 kcal/mol, implying that their frequent incidence in multiples, especially, in short sequences could even hinder triplex formation. The results provide (i an unambiguous and generalised mechanistic rationale for the discriminatory trait of parallel triplexes, including those studied experimentally (ii clarity for the prevalence of antiparallel triplexes and (iii comprehensive perspectives on the sequence dependent influence of nonisosteric base triplets useful in the rational design of TFO's against potential triplex target sites.

Natural selection on immune defense: A field experiment.

Science.gov (United States)

Langeloh, Laura; Behrmann-Godel, Jasminca; Seppälä, Otto

2017-02-01

Predicting the evolution of phenotypic traits requires an understanding of natural selection on them. Despite its indispensability in the fight against parasites, selection on host immune defense has remained understudied. Theory predicts immune traits to be under stabilizing selection due to associated trade-offs with other fitness-related traits. Empirical studies, however, report mainly positive directional selection. This discrepancy could be caused by low phenotypic variation in the examined individuals and/or variation in host resource level that confounds trade-offs in empirical studies. In a field experiment where we maintained Lymnaea stagnalis snails individually in cages in a lake, we investigated phenotypic selection on two immune defense traits, phenoloxidase (PO)-like activity and antibacterial activity, in hemolymph. We used a diverse laboratory population and manipulated snail resource level by limiting their food supply. For six weeks, we followed immune activity, growth, and two fitness components, survival and fecundity of snails. We found that PO-like activity and growth were under stabilizing selection, while antibacterial activity was under positive directional selection. Selection on immune traits was mainly driven by variation in survival. The form of selection on immune defense apparently depends on the particular trait, possibly due to its importance for countering the present parasite community. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Fluctuating selection on basal metabolic rate.

Science.gov (United States)

Nilsson, Johan F; Nilsson, Jan-Åke

2016-02-01

BMR (Basal metabolic rate) is an important trait in animal life history as it represents a significant part of animal energy budgets. BMR has also been shown to be positively related to sustainable work rate and maximal thermoregulatory capacity. To this date, most of the studies have focused on the causes of interspecific and intraspecific variation in BMR, and fairly little is known about the fitness consequences of different metabolic strategies. In this study, we show that winter BMR affects local survival in a population of wild blue tits (Cyanistes caeruleus), but that the selection direction differs between years. We argue that this fluctuating selection is probably a consequence of varying winter climate with a positive relation between survival and BMR during cold and harsh conditions, but a negative relation during mild winters. This fluctuating selection can not only explain the pronounced variation in BMR in wild populations, but will also give us new insights into how energy turnover rates can shape the life-history strategies of animals. Furthermore, the study shows that the process of global warming may cause directional selection for a general reduction in BMR, affecting the general life-history strategy on the population level.

Psychosocial Adaptation to Disability Within the Context of Positive Psychology: Findings from the Literature.

Science.gov (United States)

Martz, Erin; Livneh, Hanoch

2016-03-01

This purpose of this article is to review of the trends of research that examined positive psychology constructs in the context of adapting to chronic illness and disability (CID). This article examines the empirical findings on the relationships between six selected positive psychology-associated constructs (optimism, hope, resilience, benefit-finding, meaning-making, and post-traumatic growth) and adaptation to disability. Six positive psychology constructs were selected to represent the trends found in recent literature published on CID. The process of choosing these six variables included reviewing chapters on positive psychology and CID, reviewing the top rehabilitation journals that typically publish articles on psychosocial adaptation to CID, using search engines to find relevant journal articles published since the year 2000, and selecting the most important constructs based on the authors’ professional judgment. The available evidence supports the unique benefits of these six positive psychology constructs in predicting successful adaptation to a range of disabling conditions. Based on the available findings, the authors offer four suggestions for occupational rehabilitation researchers.

Classification of positive blood cultures

DEFF Research Database (Denmark)

Gradel, Kim Oren; Knudsen, Jenny Dahl; Arpi, Magnus

2012-01-01

. For each classification, we tabulated episodes derived by the physicians assessment and the computer algorithm and compared 30-day mortality between concordant and discrepant groups with adjustment for age, gender, and comorbidity. RESULTS: Physicians derived 9,482 reference episodes from 21,705 positive......- vs. hospitalonset, whereas there were no material differences within the other comparison groups. CONCLUSIONS: Using data from health administrative registries, we found high agreement between the computer algorithms and the physicians assessments as regards contamination vs. bloodstream infection......ABSTRACT: BACKGROUND: Information from blood cultures is utilized for infection control, public health surveillance, and clinical outcome research. This information can be enriched by physicians assessments of positive blood cultures, which are, however, often available from selected patient groups...

Light Reflectance Spectroscopy to Detect Positive Surgical Margins on Prostate Cancer Specimens.

Science.gov (United States)

Morgan, Monica S C; Lay, Aaron H; Wang, Xinlong; Kapur, Payal; Ozayar, Asim; Sayah, Maryam; Zeng, Li; Liu, Hanli; Roehrborn, Claus G; Cadeddu, Jeffrey A

2016-02-01

Intraoperative frozen section analysis is not routinely performed to determine positive surgical margins at radical prostatectomy due to time requirements and unproven clinical usefulness. Light reflectance spectroscopy, which measures light intensity reflected or backscattered from tissues, can be applied to differentiate malignant from benign tissue. We used a novel light reflectance spectroscopy probe to evaluate positive surgical margins on ex vivo radical prostatectomy specimens and correlate its findings with pathological examination. Patients with intermediate to high risk disease undergoing radical prostatectomy were enrolled. Light reflectance spectroscopy was performed on suspected malignant and benign prostate capsule immediately following organ extraction. Each light reflectance spectroscopy at 530 to 830 nm was analyzed and correlated with pathological results. A regression model and forward sequential selection algorithm were developed for optimal feature selection. Eighty percent of light reflectance spectroscopy data were selected to train a logistic regression model, which was evaluated by the remaining 20% data. This was repeated 5 times to calculate averaged sensitivity, specificity and accuracy. Light reflectance spectroscopy analysis was performed on 17 ex vivo prostate specimens, on which a total of 11 histologically positive and 22 negative surgical margins were measured. Two select features from 700 to 830 nm were identified as unique to malignant tissue. Cross-validation when performing the predictive model showed that the optical probe predicted positive surgical margins with 85% sensitivity, 86% specificity, 86% accuracy and an AUC of 0.95. Light reflectance spectroscopy can identify positive surgical margins accurately in fresh ex vivo radical prostatectomy specimens. Further study is required to determine whether such analysis may be used in real time to improve surgical decision making and decrease positive surgical margin rates

Intrinsic incompatibilities evolving as a by-product of divergent ecological selection: Considering them in empirical studies on divergence with gene flow.

Science.gov (United States)

Kulmuni, J; Westram, A M

2017-06-01

The possibility of intrinsic barriers to gene flow is often neglected in empirical research on local adaptation and speciation with gene flow, for example when interpreting patterns observed in genome scans. However, we draw attention to the fact that, even with gene flow, divergent ecological selection may generate intrinsic barriers involving both ecologically selected and other interacting loci. Mechanistically, the link between the two types of barriers may be generated by genes that have multiple functions (i.e., pleiotropy), and/or by gene interaction networks. Because most genes function in complex networks, and their evolution is not independent of other genes, changes evolving in response to ecological selection can generate intrinsic barriers as a by-product. A crucial question is to what extent such by-product barriers contribute to divergence and speciation-that is whether they stably reduce gene flow. We discuss under which conditions by-product barriers may increase isolation. However, we also highlight that, depending on the conditions (e.g., the amount of gene flow and the strength of selection acting on the intrinsic vs. the ecological barrier component), the intrinsic incompatibility may actually destabilize barriers to gene flow. In practice, intrinsic barriers generated as a by-product of divergent ecological selection may generate peaks in genome scans that cannot easily be interpreted. We argue that empirical studies on divergence with gene flow should consider the possibility of both ecological and intrinsic barriers. Future progress will likely come from work combining population genomic studies, experiments quantifying fitness and molecular studies on protein function and interactions. © 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Numerical study on the selective excitation of Helmholtz-Gauss beams in end-pumped solid-state digital lasers with the control of the laser gain transverse position provided by off-axis end pumping

Science.gov (United States)

Tsai, Ko-Fan; Chu, Shu-Chun

2018-03-01

This study proposes a complete and unified method for selective excitation of any specified nearly nondiffracting Helmholtz-Gauss (HzG) beam in end-pumped solid-state digital lasers. Four types of the HzG beams: cosine-Gauss beams, Bessel-Gauss beams, Mathieu-Gauss beams, and, in particular, parabolic-Gauss beams are successfully demonstrated to be generated with the proposed methods. To the best of the authors’ knowledge, parabolic-Gauss beams have not yet been directly generated from any kind of laser system. The numerical results of this study show that one can successfully achieve any lasing HzG beams directly from the solid-state digital lasers with only added control of the laser gain transverse position provided by off-axis end pumping. This study also presents a practical digital laser set-up for easily manipulating off-axis pumping in order to achieve the control of the laser gain transverse gain position in digital lasers. The reported results in this study provide advancement of digital lasers in dynamically generating nondiffracting beams. The control of the digital laser cavity gain position creates the possibility of achieving real-time selection of more laser modes in digital lasers, and it is worth further investigation in the future.

Site suitability, selection and characterization: Branch technical position--Low-Level Waste Licensing Branch

International Nuclear Information System (INIS)

Siefken, D.; Pangburn, G.; Pennifill, R.; Starmer, R.J.

1982-04-01

The staff provides an expanded interpretation of the site suitability requirements in the proposed rule 10 CFR Part 61, a description of the anticipated site selection process, and a detailed discussion of the site characterization program needed to support a license application and environmental report. The paper provides early-on guidance to prospective applicants in these three subject areas

Positive selection in the leucine-rich repeat domain of Gro1 genes in ...

Indian Academy of Sciences (India)

history during which the main structure of the domain has been conserved such that ... from the column using 100 μL of distilled water. The LRR fragments from the ... ture of the domain and to obtain the best PDB template for mapping positive ...

Gender Wage Gap Accounting: The Role of Selection Bias.

Science.gov (United States)

Bar, Michael; Kim, Seik; Leukhina, Oksana

2015-10-01

Mulligan and Rubinstein (2008) (MR) argued that changing selection of working females on unobservable characteristics, from negative in the 1970s to positive in the 1990s, accounted for nearly the entire closing of the gender wage gap. We argue that their female wage equation estimates are inconsistent. Correcting this error substantially weakens the role of the rising selection bias (39 % versus 78 %) and strengthens the contribution of declining discrimination (42 % versus 7 %). Our findings resonate better with related literature. We also explain why our finding of positive selection in the 1970s provides additional support for MR's main hypothesis that an exogenous rise in the market value of unobservable characteristics contributed to the closing of the gender gap.

Detecting directional selection in the presence of recent admixture in African-Americans.

Science.gov (United States)

Lohmueller, Kirk E; Bustamante, Carlos D; Clark, Andrew G

2011-03-01

We investigate the performance of tests of neutrality in admixed populations using plausible demographic models for African-American history as well as resequencing data from African and African-American populations. The analysis of both simulated and human resequencing data suggests that recent admixture does not result in an excess of false-positive results for neutrality tests based on the frequency spectrum after accounting for the population growth in the parental African population. Furthermore, when simulating positive selection, Tajima's D, Fu and Li's D, and haplotype homozygosity have lower power to detect population-specific selection using individuals sampled from the admixed population than from the nonadmixed population. Fay and Wu's H test, however, has more power to detect selection using individuals from the admixed population than from the nonadmixed population, especially when the selective sweep ended long ago. Our results have implications for interpreting recent genome-wide scans for positive selection in human populations. © 2011 by the Genetics Society of America

Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

Science.gov (United States)

Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

2011-10-01

A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

Optimized positioning of autonomous surgical lamps

Science.gov (United States)

Teuber, Jörn; Weller, Rene; Kikinis, Ron; Oldhafer, Karl-Jürgen; Lipp, Michael J.; Zachmann, Gabriel

2017-03-01

We consider the problem of finding automatically optimal positions of surgical lamps throughout the whole surgical procedure, where we assume that future lamps could be robotized. We propose a two-tiered optimization technique for the real-time autonomous positioning of those robotized surgical lamps. Typically, finding optimal positions for surgical lamps is a multi-dimensional problem with several, in part conflicting, objectives, such as optimal lighting conditions at every point in time while minimizing the movement of the lamps in order to avoid distractions of the surgeon. Consequently, we use multi-objective optimization (MOO) to find optimal positions in real-time during the entire surgery. Due to the conflicting objectives, there is usually not a single optimal solution for such kinds of problems, but a set of solutions that realizes a Pareto-front. When our algorithm selects a solution from this set it additionally has to consider the individual preferences of the surgeon. This is a highly non-trivial task because the relationship between the solution and the parameters is not obvious. We have developed a novel meta-optimization that considers exactly this challenge. It delivers an easy to understand set of presets for the parameters and allows a balance between the lamp movement and lamp obstruction. This metaoptimization can be pre-computed for different kinds of operations and it then used by our online optimization for the selection of the appropriate Pareto solution. Both optimization approaches use data obtained by a depth camera that captures the surgical site but also the environment around the operating table. We have evaluated our algorithms with data recorded during a real open abdominal surgery. It is available for use for scientific purposes. The results show that our meta-optimization produces viable parameter sets for different parts of an intervention even when trained on a small portion of it.

Context Aware Handover Algorithms For Mobile Positioning Systems

Directory of Open Access Journals (Sweden)

Sazid Z. Khan

2014-01-01

Full Text Available Abstract: This work proposes context aware handover algorithms for mobile positioning systems. The algorithms perform handover among positioning systems based on important contextual factors related to position determination with efficient use of battery. The proposed solution which consists of the algorithms is implemented in the form of an Android application named Locate@nav6. The performance of the proposed solution was tested in selected experimental areas. The handover performance was compared with other existing location applications. The proposed solution performed correct handover among positioning systems in 95% of cases studied while two other applications performed correct handover in only 50% of cases studied. Battery usage of the proposed solution is less than one third of the battery usage of two other applications. The analysis of the positioning error of the applications demonstrated that, the proposed solution is able to reduce positioning error indirectly by handing over the task of positioning to an appropriate positioning system. This kept the average error of positioning below 42.1 meters for Locate@nav6 while the average error for two other applications namely Google Latitude and Malaysia maps was between 92.7 and 171.13 meters.

Evaluating the effectiveness of brand-positioning strategies from a consumer perspective

DEFF Research Database (Denmark)

Fuchs, Christoph; Diamantopoulos, Adamantios

2010-01-01

- The findings should guide brand managers in selecting the most appropriate positioning strategies for their brands in high-involvement markets such as the automobile market. Originality/value - The study sheds initial light on the overall relative effectiveness of major positioning strategies. The study......Purpose - The purpose of the paper is to explore empirically the overall relative effectiveness of alternative positioning strategies from a consumer perspective. Design/methodology/approach - Two studies (within- and between-subjects design) are conducted aimed at evaluating the positioning...... of positioning strategy used affects the positioning success of a brand. More specifically, the study confirms normative arguments about the overall relative effectiveness of main positioning strategies by revealing that benefit-based positioning and surrogate (user) positioning generally outperform feature...

Detection of Fundus Lesions Using Classifier Selection

Science.gov (United States)

Nagayoshi, Hiroto; Hiramatsu, Yoshitaka; Sako, Hiroshi; Himaga, Mitsutoshi; Kato, Satoshi

A system for detecting fundus lesions caused by diabetic retinopathy from fundus images is being developed. The system can screen the images in advance in order to reduce the inspection workload on doctors. One of the difficulties that must be addressed in completing this system is how to remove false positives (which tend to arise near blood vessels) without decreasing the detection rate of lesions in other areas. To overcome this difficulty, we developed classifier selection according to the position of a candidate lesion, and we introduced new features that can distinguish true lesions from false positives. A system incorporating classifier selection and these new features was tested in experiments using 55 fundus images with some lesions and 223 images without lesions. The results of the experiments confirm the effectiveness of the proposed system, namely, degrees of sensitivity and specificity of 98% and 81%, respectively.

Ionoluminscence of partially-stabilized zirconia for thermal barrier coatings

International Nuclear Information System (INIS)

Rebollo, N.R.; Ruvalcaba-Sil, J.L.; Miranda, J.

2007-01-01

Ionoluminescence is explored as an alternative technique to study the high temperature phase stability of zirconia-based oxides. The evolution of an initially metastable single tetragonal phase towards de-stabilization is investigated for three single-doped zirconia compositions with Y, Yb and Gd. The differences in de-stabilization paths are identified using X-ray diffraction and ionoluminescence; elemental analysis is also performed using particle-induced X-ray emission. X-ray diffraction studies reveal a different scenario for each of the compositions selected; the differences are strongly influenced by the thermodynamic driving forces associated to the fluorite-to-tetragonal displacive transformation. Ionoluminescence studies indicate a significant increment on the signal intensity for de-stabilized samples, relative to previous annealing stages. There are also more subtle differences in the luminescent response from the samples at intermediate annealing stages also related to phase changes. This study provides a basis to characterize phase evolution in single-doped zirconia compositions for thermal insulation applications using luminescence

Emotional bias of sleep-dependent processing shifts from negative to positive with aging.

Science.gov (United States)

Jones, Bethany J; Schultz, Kurt S; Adams, Sydney; Baran, Bengi; Spencer, Rebecca M C

2016-09-01

Age-related memory decline has been proposed to result partially from impairments in memory consolidation over sleep. However, such decline may reflect a shift toward selective processing of positive information with age rather than impaired sleep-related mechanisms. In the present study, young and older adults viewed negative and neutral pictures or positive and neutral pictures and underwent a recognition test after sleep or wake. Subjective emotional reactivity and affect were also measured. Compared with waking, sleep preserved valence ratings and memory for positive but not negative pictures in older adults and negative but not positive pictures in young adults. In older adults, memory for positive pictures was associated with slow wave sleep. Furthermore, slow wave sleep predicted positive affect in older adults but was inversely related to positive affect in young adults. These relationships were strongest for older adults with high memory for positive pictures and young adults with high memory for negative pictures. Collectively, these results indicate preserved but selective sleep-dependent memory processing with healthy aging that may be biased to enhance emotional well-being. Copyright © 2016 Elsevier Inc. All rights reserved.

Population Genetics and Natural Selection in Rheumatic Disease.

Science.gov (United States)

Ramos, Paula S

2017-08-01

Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Natural selection is an important influence on human genetic variation. Because immune and inflammatory function genes are enriched for signals of positive selection, the prevalence of rheumatic disease-risk alleles seen in different populations is partially the result of differing selective pressures (eg, due to pathogens). This review summarizes the genetic regions associated with susceptibility to different rheumatic diseases and concomitant evidence for natural selection, including known agents of selection exerting selective pressure in these regions. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-E-J-21: Setup Variability of Colorectal Cancer Patients Treated in the Prone Position and Dosimetric Comparison with the Supine Position

Energy Technology Data Exchange (ETDEWEB)

Kim, A; Foster, J; Chu, W; Karotki, A [Sunnybrook Health Sciences Centre/Odette Cancer Centre, Toronto, Ontario (Canada)

2015-06-15

Purpose: Many cancer centers treat colorectal patients in the prone position on a belly board to minimize dose to the small bowel. That may potentially Result in patient setup instability with corresponding impact on dose delivery accuracy for highly conformal techniques such as IMRT/VMAT. Two aims of this work are 1) to investigate setup accuracy of rectum patients treated in the prone position on a belly board using CBCT and 2) to evaluate dosimetric impact on bladder and small bowel of treating rectum patients in supine vs. prone position. Methods: For the setup accuracy study, 10 patients were selected. Weekly CBCTs were acquired and matched to bone. The CBCT-determined shifts were recorded. For the dosimetric study, 7 prone-setup patients and 7 supine-setup patients were randomly selected from our clinical database. Various clinically relevant dose volume histogram values were recorded for the small bowel and bladder. Results: The CBCT-determined rotational shifts had a wide variation. For the dataset acquired at the time of this writing, the ranges of rotational setup errors for pitch, roll, and yaw were [−3.6° 4.7°], [−4.3° 3.2°], and [−1.4° 1.4°]. For the dosimetric study: the small bowel V(45Gy) and mean dose for the prone position was 5.6±12.1% and 18.4±6.2Gy (ranges indicate standard deviations); for the supine position the corresponding dose values were 12.9±15.8% and 24.7±8.8Gy. For the bladder, the V(30Gy) and mean dose for prone position were 68.7±12.7% and 38.4±3.3Gy; for supine position these dose values were 77.1±13.7% and 40.7±3.1Gy. Conclusion: There is evidence of significant rotational instability in the prone position. The OAR dosimetry study indicates that there are some patients that may still benefit from the prone position, though many patients can be safely treated supine.

DESTABILIZATION OF A SOLAR PROMINENCE/FILAMENT FIELD SYSTEM BY A SERIES OF EIGHT HOMOLOGOUS ERUPTIVE FLARES LEADING TO A CME

Energy Technology Data Exchange (ETDEWEB)

Panesar, Navdeep K.; Moore, Ronald L. [Center for Space Plasma and Aeronomic Research (CSPAR), UAH, Huntsville, AL 35805 (United States); Sterling, Alphonse C. [Heliophysics and Planetary Science Office, ZP13, Marshall Space Flight Center, Huntsville, AL 35812 (United States); Innes, Davina E., E-mail: navdeep.k.panesar@nasa.gov [Max Planck Institut für Sonnensystemforschung, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany)

2015-09-20

Homologous flares are flares that occur repetitively in the same active region, with similar structure and morphology. A series of at least eight homologous flares occurred in active region NOAA 11237 over 2011 June 16–17. A nearby prominence/filament was rooted in the active region, and situated near the bottom of a coronal cavity. The active region was on the southeast solar limb as seen from the Solar Dynamics Observatory/Atmospheric Imaging Assembly, and on the disk as viewed from the Solar TErrestrial RElations Observatory/EUVI-B. The dual perspective allows us to study in detail behavior of the prominence/filament material entrained in the magnetic field of the repeatedly erupting system. Each of the eruptions were mainly confined, but expelled hot material into the prominence/filament cavity system (PFCS). The field carrying and containing the ejected hot material interacted with the PFCS and caused it to inflate, resulting in a step-wise rise of the PFCS approximately in step with the homologous eruptions. The eighth eruption triggered the PFCS to move outward slowly, accompanied by a weak coronal dimming. As this slow PFCS eruption was underway, a final “ejective” flare occurred in the core of the active region, resulting in strong dimming in the EUVI-B images and expulsion of a coronal mass ejection (CME). A plausible scenario is that the repeated homologous flares could have gradually destabilized the PFCS, and its subsequent eruption removed field above the acitive region and in turn led to the ejective flare, strong dimming, and CME.

Subset Selection by Local Convex Approximation

DEFF Research Database (Denmark)

Øjelund, Henrik; Sadegh, Payman; Madsen, Henrik

1999-01-01

This paper concerns selection of the optimal subset of variables in a lenear regression setting. The posed problem is combinatiorial and the globally best subset can only be found in exponential time. We define a cost function for the subset selection problem by adding the penalty term to the usual...... of the subset selection problem so as to guarantee positive definiteness of the Hessian term, hence avoiding numerical instability. The backward Elemination type algorithm attempts to improve the results upon termination of the modified Newton-Raphson search by sing the current solution as an initial guess...

Beam position monitor system for storage rings

International Nuclear Information System (INIS)

Nakamura, M.; Hinkson, J.A.

1985-05-01

Beam position monitors (BPM) for synchrotron light storage rings usually consist of beam pickup electrodes, coaxial relays and a narrowband receiver. While accurate, these systems are slow and of limited use in the commissioning of an accelerator. A beam position monitor is described which is intended to be a principal diagnostic during debug and routine running of a storage ring. It is capable of measuring the position of a single bunch on the first or nth orbit to an accuracy of a few percent. Stored beam position is more accurately measured with averaging techniques. Beam position changes can be studied in a bandwidth from DC to a few MHz. The beam monitor electronics consist of a separate amplification, detection, and sampling channel for each beam pickup electrode. Fast switches in each channel permit selection of the nth turn for measurement (single bunch mode). A calibration pulse is injected into each channel after beam measurement to permit gain offsets to be measured and removed from the final data. While initially more costly than the usual beam position monitor system, this sytem will pay for itself in reduced storage ring debug and trouble shooting time. 5 refs., 5 figs

Supplier selection using different metric functions

Directory of Open Access Journals (Sweden)

Omosigho S.E.

2015-01-01

Full Text Available Supplier selection is an important component of supply chain management in today’s global competitive environment. Hence, the evaluation and selection of suppliers have received considerable attention in the literature. Many attributes of suppliers, other than cost, are considered in the evaluation and selection process. Therefore, the process of evaluation and selection of suppliers is a multi-criteria decision making process. The methodology adopted to solve the supplier selection problem is intuitionistic fuzzy TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution. Generally, TOPSIS is based on the concept of minimum distance from the positive ideal solution and maximum distance from the negative ideal solution. We examine the deficiencies of using only one metric function in TOPSIS and propose the use of spherical metric function in addition to the commonly used metric functions. For empirical supplier selection problems, more than one metric function should be used.

Immediate movement history influences reach-to-grasp action selection in children and adults.