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Sample records for evolutionary mechanisms involved

  1. Evolutionary mechanisms involved in the virulence of infectious salmon anaemia virus (ISAV), a piscine orthomyxovirus

    International Nuclear Information System (INIS)

    Markussen, Turhan; Jonassen, Christine Monceyron; Numanovic, Sanela; Braaen, Stine; Hjortaas, Monika; Nilsen, Hanne; Mjaaland, Siri

    2008-01-01

    Infectious salmon anaemia virus (ISAV) is an orthomyxovirus causing a multisystemic, emerging disease in Atlantic salmon. Here we present, for the first time, detailed sequence analyses of the full-genome sequence of a presumed avirulent isolate displaying a full-length hemagglutinin-esterase (HE) gene (HPR0), and compare this with full-genome sequences of 11 Norwegian ISAV isolates from clinically diseased fish. These analyses revealed the presence of a virulence marker right upstream of the putative cleavage site R 267 in the fusion (F) protein, suggesting a Q 266 → L 266 substitution to be a prerequisite for virulence. To gain virulence in isolates lacking this substitution, a sequence insertion near the cleavage site seems to be required. This strongly suggests the involvement of a protease recognition pattern at the cleavage site of the fusion protein as a determinant of virulence, as seen in highly pathogenic influenza A virus H5 or H7 and the paramyxovirus Newcastle disease virus

  2. Evolutionary Mechanisms Involved in Emergence of Viral Haemorrhagic Septicaemia Virus (VHSV) into Cultured Rainbow Trout, Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Schönherz, Anna A.

    virulence, causing extensive losses to the aquacultre industry. Cross-species transmission and subsequent adaptation to cultured raibow trout is observed occasionally. However, the biological background facilitationg VHSV emergense has yet to be identified. In the present PhD project potential mechanisms...... facilitation VHSV emergence into cultured raibow trout were explored. In vivo infection trials and in selico based molecular analysis were performed to independently investigate the first two steps of viral emergence, namely initial introduction to- and subsequent adaptation and establishment within the new...... of genetic variation, and that VHSV emergence into cultured rainbow torut was accompanied by rapid adaptive evolution within the viral glucoprotein...

  3. Quantum Mechanics predicts evolutionary biology.

    Science.gov (United States)

    Torday, J S

    2018-07-01

    Nowhere are the shortcomings of conventional descriptive biology more evident than in the literature on Quantum Biology. In the on-going effort to apply Quantum Mechanics to evolutionary biology, merging Quantum Mechanics with the fundamentals of evolution as the First Principles of Physiology-namely negentropy, chemiosmosis and homeostasis-offers an authentic opportunity to understand how and why physics constitutes the basic principles of biology. Negentropy and chemiosmosis confer determinism on the unicell, whereas homeostasis constitutes Free Will because it offers a probabilistic range of physiologic set points. Similarly, on this basis several principles of Quantum Mechanics also apply directly to biology. The Pauli Exclusion Principle is both deterministic and probabilistic, whereas non-localization and the Heisenberg Uncertainty Principle are both probabilistic, providing the long-sought after ontologic and causal continuum from physics to biology and evolution as the holistic integration recognized as consciousness for the first time. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Algorithmic Mechanism Design of Evolutionary Computation.

    Science.gov (United States)

    Pei, Yan

    2015-01-01

    We consider algorithmic design, enhancement, and improvement of evolutionary computation as a mechanism design problem. All individuals or several groups of individuals can be considered as self-interested agents. The individuals in evolutionary computation can manipulate parameter settings and operations by satisfying their own preferences, which are defined by an evolutionary computation algorithm designer, rather than by following a fixed algorithm rule. Evolutionary computation algorithm designers or self-adaptive methods should construct proper rules and mechanisms for all agents (individuals) to conduct their evolution behaviour correctly in order to definitely achieve the desired and preset objective(s). As a case study, we propose a formal framework on parameter setting, strategy selection, and algorithmic design of evolutionary computation by considering the Nash strategy equilibrium of a mechanism design in the search process. The evaluation results present the efficiency of the framework. This primary principle can be implemented in any evolutionary computation algorithm that needs to consider strategy selection issues in its optimization process. The final objective of our work is to solve evolutionary computation design as an algorithmic mechanism design problem and establish its fundamental aspect by taking this perspective. This paper is the first step towards achieving this objective by implementing a strategy equilibrium solution (such as Nash equilibrium) in evolutionary computation algorithm.

  5. Statistical mechanics of spatial evolutionary games

    International Nuclear Information System (INIS)

    Miekisz, Jacek

    2004-01-01

    We discuss the long-run behaviour of stochastic dynamics of many interacting players in spatial evolutionary games. In particular, we investigate the effect of the number of players and the noise level on the stochastic stability of Nash equilibria. We discuss similarities and differences between systems of interacting players maximizing their individual payoffs and particles minimizing their interaction energy. We use concepts and techniques of statistical mechanics to study game-theoretic models. In order to obtain results in the case of the so-called potential games, we analyse the thermodynamic limit of the appropriate models of interacting particles

  6. Anticipatory Mechanisms in Evolutionary Living Systems

    Science.gov (United States)

    Dubois, Daniel M.; Holmberg, Stig C.

    2010-11-01

    This paper deals firstly with a revisiting of Darwin's theory of Natural Selection. Darwin in his book never uses the word "evolution", but shows a clear position about mutability of species. Darwin's Natural Selection was mainly inspired by the anticipatory Artificial Selection by humans in domestication, and the Malthus struggle for existence. Darwin showed that the struggle for existence leads to the preservation of the most divergent offspring of any one species. He cited several times the canon of "Natura non facit saltum". He spoke about the origin of life from some one primordial form, into which life was first breathed. Finally, Darwin made anticipation about the future researches in psychology. This paper cites the work of Ernst Mayr who was the first, after 90 years of an intense scientific debate, to present a new and stable Darwinian paradigm as the "Evolutionary Synthesis" in 1942. To explain what is life, the Living Systems Theory (LST) by J. G. Miller is presented. It is showed that the Autopoietic Systems Theory of Varela et al is also a fundamental component of living systems. In agreement with Darwin, the natural selection is a necessary condition for transformation of biological systems, but is not a sufficient condition. Thus, in this paper we conjecture that an anticipatory evolutionary mechanism exists with the genetic code that is a self-replicating and self-modifying anticipatory program. As demonstrated by Nobel laureate McClintock, evolution in genomes is programmed. The word "program" comes from "pro-gram" meaning to write before, by anticipation, and means a plan for the programming of a mechanism, or a sequence of coded instructions that can be inserted into a mechanism, or a sequence of coded instructions, as genes of behavioural responses, that is part of an organism. For example, cell death may be programmed by what is called the apoptosis. This definitively is a great breakthrough in our understanding of biological evolution. Hence

  7. The evolution of different forms of sociality: behavioral mechanisms and eco-evolutionary feedback.

    Directory of Open Access Journals (Sweden)

    Daniel J van der Post

    Full Text Available Different forms of sociality have evolved via unique evolutionary trajectories. However, it remains unknown to what extent trajectories of social evolution depend on the specific characteristics of different species. Our approach to studying such trajectories is to use evolutionary case-studies, so that we can investigate how grouping co-evolves with a multitude of individual characteristics. Here we focus on anti-predator vigilance and foraging. We use an individual-based model, where behavioral mechanisms are specified, and costs and benefits are not predefined. We show that evolutionary changes in grouping alter selection pressures on vigilance, and vice versa. This eco-evolutionary feedback generates an evolutionary progression from "leader-follower" societies to "fission-fusion" societies, where cooperative vigilance in groups is maintained via a balance between within- and between-group selection. Group-level selection is generated from an assortment that arises spontaneously when vigilant and non-vigilant foragers have different grouping tendencies. The evolutionary maintenance of small groups, and cooperative vigilance in those groups, is therefore achieved simultaneously. The evolutionary phases, and the transitions between them, depend strongly on behavioral mechanisms. Thus, integrating behavioral mechanisms and eco-evolutionary feedback is critical for understanding what kinds of intermediate stages are involved during the evolution of particular forms of sociality.

  8. SPICA/SAFARI Fourier transform spectrometer mechanism evolutionary design

    Science.gov (United States)

    van den Dool, Teun C.; Kruizinga, Bob; Braam, Ben C.; Hamelinck, Roger F. M. M.; Loix, Nicolas; Van Loon, Dennis; Dams, Johan

    2012-09-01

    TNO, together with its partners, have designed a cryogenic scanning mechanism for use in the SAFARI1 Fourier Transform Spectrometer (FTS) on board of the SPICA mission. SPICA is one of the M-class missions competing to be launched in ESA's Cosmic Vision Programme2 in 2022. JAXA3 leads the development of the SPICA satellite and SRON is the prime investigator of the Safari instrument. The FTS scanning mechanism (FTSM) has to meet a 35 mm stroke requirement with an Optical Path Difference resolution of less then 15 nm and must fit in a small volume. It consists of two back-to-back roof-top mirrors mounted on a small carriage, which is moved using a magnetic bearing linear guiding system in combination with a magnetic linear motor serving as the OPD actuator. The FTSM will be used at cryogenic temperatures of 4 Kelvin inducing challenging requirements on the thermal power dissipation and heat leak. The magnetic bearing enables movements over a scanning stroke of 35.5 mm in a small volume. It supports the optics in a free-floating way with no friction, or other non-linearities, with sub-nanometer accuracy. This solution is based on the design of the breadboard ODL (Optical Delay Line) developed for the ESA Darwin mission4 and the MABE mechanism developed by Micromega Dynamics. During the last couple of years the initial design of the SAFARI instrument, as described in an earlier SPIE 2010 paper5, was adapted by the SAFARI team in an evolutionary way to meet the changing requirements of the SPICA payload module. This presentation will focus on the evolution of the FTSM to meet these changing requirements. This work is supported by the Netherlands Space Office (NSO).

  9. The mechanisms involved at the cell level

    International Nuclear Information System (INIS)

    Leblanc, G.; Pourcher, Th.; Perron, B.; Guillain, F.; Quemeneur, E.; Fritsch, P.

    2003-01-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

  10. Service user involvement in mental health care: an evolutionary concept analysis.

    Science.gov (United States)

    Millar, Samantha L; Chambers, Mary; Giles, Melanie

    2016-04-01

    The concept of service user involvement is an evolving concept in the mental health-care literature. This study sought to explore and analyse the concept of service user involvement as used in within the field of mental health care. An evolutionary concept analysis was conducted using a literature-based sample extracted from an electronic database search. One hundred and thirty-four papers met the inclusion criteria and were analysed to discover key attributes, antecedents and consequences of service user involvement and to produce a definition of the concept. Five key attributes of service user involvement within the context of mental health care were identified: a person-centred approach, informed decision making, advocacy, obtaining service user views and feedback and working in partnership. Clarity of the attributes and definition of the concept of service user involvement aims to promote understanding of the concept among key stakeholders including mental health professionals, service users and community and voluntary organizations. The findings of the research have utility in the areas of theory and policy development, research on service user involvement in mental health care and service user involvement in mental health practice. Directions for further research regarding the concept are identified. © 2015 John Wiley & Sons Ltd.

  11. Dual transcriptomics reveals co-evolutionary mechanisms of intestinal parasite infections in blue mussels Mytilus edulis

    NARCIS (Netherlands)

    Feis, M.E.; John, U.; Lokmer, A.; Luttikhuizen, P.C.; Wegner, K.M.

    2018-01-01

    On theoretical grounds, antagonistic co-evolution between hosts and their parasitesshould be a widespread phenomenon but only received little empirical support sofar. Consequently, the underlying molecular mechanisms and evolutionary stepsremain elusive, especially in nonmodel systems. Here, we

  12. Sex differences in jealousy: evolutionary mechanism or artifact of measurement?

    Science.gov (United States)

    DeSteno, David; Bartlett, Monica Y; Braverman, Julia; Salovey, Peter

    2002-11-01

    Two studies are presented that challenge the evidentiary basis for the existence of evolved sex differences in jealousy. In opposition to the evolutionary view, Study I demonstrated that a sex difference in jealousy resulting from sexual versus emotional infidelity is observed only when judgments are recorded using a forced-choice response format. On all other measures, no sex differences were found; both men and women reported greater jealousy in response to sexual infidelity. A second study revealed that the sex difference on the forced-choice measure disappeared under conditions of cognitive constraint. These findings suggest that the sex difference used to support the evolutionary view of jealousy (e.g., D. M. Buss, R. Larsen, D. Westen, & J. Semmelroth, 1992; D. M. Buss et al., 1999) likely represents a measurement artifact resulting from a format-induced effortful decision strategy and not an automatic, sex-specific response shaped by evolution.

  13. Neurobiological mechanisms involved in sleep bruxism.

    Science.gov (United States)

    Lavigne, G J; Kato, T; Kolta, A; Sessle, B J

    2003-01-01

    Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

  14. Mechanics of evolutionary digit reduction in fossil horses (Equidae).

    Science.gov (United States)

    McHorse, Brianna K; Biewener, Andrew A; Pierce, Stephanie E

    2017-08-30

    Digit reduction is a major trend that characterizes horse evolution, but its causes and consequences have rarely been quantitatively tested. Using beam analysis on fossilized centre metapodials, we tested how locomotor bone stresses changed with digit reduction and increasing body size across the horse lineage. Internal bone geometry was captured from 13 fossil horse genera that covered the breadth of the equid phylogeny and the spectrum of digit reduction and body sizes, from Hyracotherium to Equus To account for the load-bearing role of side digits, a novel, continuous measure of digit reduction was also established-toe reduction index (TRI). Our results show that without accounting for side digits, three-toed horses as late as Parahippus would have experienced physiologically untenable bone stresses. Conversely, when side digits are modelled as load-bearing, species at the base of the horse radiation through Equus probably maintained a similar safety factor to fracture stress. We conclude that the centre metapodial compensated for evolutionary digit reduction and body mass increases by becoming more resistant to bending through substantial positive allometry in internal geometry. These results lend support to two historical hypotheses: that increasing body mass selected for a single, robust metapodial rather than several smaller ones; and that, as horse limbs became elongated, the cost of inertia from the side toes outweighed their utility for stabilization or load-bearing. © 2017 The Author(s).

  15. Molecular mechanisms involved in convergent crop domestication.

    Science.gov (United States)

    Lenser, Teresa; Theißen, Günter

    2013-12-01

    Domestication has helped to understand evolution. We argue that, vice versa, novel insights into evolutionary principles could provide deeper insights into domestication. Molecular analyses have demonstrated that convergent phenotypic evolution is often based on molecular changes in orthologous genes or pathways. Recent studies have revealed that during plant domestication the causal mutations for convergent changes in key traits are likely to be located in particular genes. These insights may contribute to defining candidate genes for genetic improvement during the domestication of new plant species. Such efforts may help to increase the range of arable crops available, thus increasing crop biodiversity and food security to help meet the predicted demands of the continually growing global population under rapidly changing environmental conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Study on Cooperative Mechanism of Prefabricated Producers Based on Evolutionary Game Theory

    Directory of Open Access Journals (Sweden)

    Tongyao Feng

    2017-01-01

    Full Text Available Good cooperation mechanism is an important guarantee for the advancement of industrialization construction. To strengthen the partnership between producers, we analyze the behavior evolution trend of both parties using an evolutionary game theory. Based on the original model, the mechanism of coordination and cooperation between prefabricated producers is explained under the condition of punishment and incentive. The results indicate that stable evolutionary strategies exist under both cooperation and noncooperation, and the evolutionary results are influenced by the initial proportion of both decision-making processes. The government can support the production enterprises to establish a solid partnership through effective punishment and incentive mechanisms to reduce the initial cost in the supply chain of prefabricated construction, resulting in a win-win situation.

  17. SPICA/SAFARI fourier transform spectrometer mechanism evolutionary design

    NARCIS (Netherlands)

    Dool, T.C. van den; Kruizinga, B.; Braam, B.C.; Hamelinck, R.F.M.M.; Loix, N.; Loon, D. van; Dams, J.

    2012-01-01

    TNO, together with its partners, have designed a cryogenic scanning mechanism for use in the SAFARI Fourier Transform Spectrometer (FTS) on board of the SPICA mission. SPICA is one of the M-class missions competing to be launched in ESA's Cosmic Vision Programme in 2022. JAXA leads the development

  18. Symmetry-based reciprocity: evolutionary constraints on a proximate mechanism.

    Science.gov (United States)

    Campennì, Marco; Schino, Gabriele

    2016-01-01

    Background. While the evolution of reciprocal cooperation has attracted an enormous attention, the proximate mechanisms underlying the ability of animals to cooperate reciprocally are comparatively neglected. Symmetry-based reciprocity is a hypothetical proximate mechanism that has been suggested to be widespread among cognitively unsophisticated animals. Methods. We developed two agent-based models of symmetry-based reciprocity (one relying on an arbitrary tag and the other on interindividual proximity) and tested their ability both to reproduce significant emergent features of cooperation in group living animals and to promote the evolution of cooperation. Results. Populations formed by agents adopting symmetry-based reciprocity showed differentiated "social relationships" and a positive correlation between cooperation given and received: two common aspects of animal cooperation. However, when reproduction and selection across multiple generations were added to the models, agents adopting symmetry-based reciprocity were outcompeted by selfish agents that never cooperated. Discussion. In order to evolve, hypothetical proximate mechanisms must be able to stand competition from alternative strategies. While the results of our simulations require confirmation using analytical methods, we provisionally suggest symmetry-based reciprocity is to be abandoned as a possible proximate mechanism underlying the ability of animals to reciprocate cooperative interactions.

  19. Evolutionary Trends in the Jaw Adductor Mechanics of Ornithischian Dinosaurs.

    Science.gov (United States)

    Nabavizadeh, Ali

    2016-03-01

    Jaw mechanics in ornithischian dinosaurs have been widely studied for well over a century. Most of these studies, however, use only one or few taxa within a given ornithischian clade as a model for feeding mechanics across the entire clade. In this study, mandibular mechanical advantages among 52 ornithischian genera spanning all subclades are calculated using 2D lever arm methods. These lever arm calculations estimate the effect of jaw shape and difference in adductor muscle line of action on relative bite forces along the jaw. Results show major instances of overlap between taxa in tooth positions at which there was highest mechanical advantage. A relatively low bite force is seen across the tooth row among thyreophorans (e.g., stegosaurs and ankylosaurs), with variation among taxa. A convergent transition occurs from a more evenly distributed bite force along the jaw in basal ornithopods and basal marginocephalians to a strong distal bite force in hadrosaurids and ceratopsids, respectively. Accordingly, adductor muscle vector angles show repeated trends from a mid-range caudodorsal orientation in basal ornithischians to a decrease in vector angles indicating more caudally oriented jaw movements in derived taxa (e.g., derived thyreophorans, basal ornithopods, lambeosaurines, pachycephalosaurs, and derived ceratopsids). Analyses of hypothetical jaw morphologies were also performed, indicating that both the coronoid process and lowered jaw joint increase moment arm length therefore increasing mechanical advantage of the jaw apparatus. Adaptive trends in craniomandibular anatomy show that ornithischians evolved more complex feeding apparatuses within different clades as well as morphological convergences between clades. © 2016 Wiley Periodicals, Inc.

  20. Evolutionary traces decode molecular mechanism behind fast pace of myosin XI

    Directory of Open Access Journals (Sweden)

    Syamaladevi Divya P

    2011-09-01

    Full Text Available Abstract Background Cytoplasmic class XI myosins are the fastest processive motors known. This class functions in high-velocity cytoplasmic streaming in various plant cells from algae to angiosperms. The velocities at which they process are ten times faster than its closest class V homologues. Results To provide sequence determinants and structural rationale for the molecular mechanism of this fast pace myosin, we have compared the sequences from myosin class V and XI through Evolutionary Trace (ET analysis. The current study identifies class-specific residues of myosin XI spread over the actin binding site, ATP binding site and light chain binding neck region. Sequences for ET analysis were accumulated from six plant genomes, using literature based text search and sequence searches, followed by triple validation viz. CDD search, string-based searches and phylogenetic clustering. We have identified nine myosin XI genes in sorghum and seven in grape by sequence searches. Both the plants possess one gene product each belonging to myosin type VIII as well. During this process, we have re-defined the gene boundaries for three sorghum myosin XI genes using fgenesh program. Conclusion Molecular modelling and subsequent analysis of putative interactions involving these class-specific residues suggest a structural basis for the molecular mechanism behind high velocity of plant myosin XI. We propose a model of a more flexible switch I region that contributes to faster ADP release leading to high velocity movement of the algal myosin XI.

  1. A security mechanism based on evolutionary game in fog computing.

    Science.gov (United States)

    Sun, Yan; Lin, Fuhong; Zhang, Nan

    2018-02-01

    Fog computing is a distributed computing paradigm at the edge of the network and requires cooperation of users and sharing of resources. When users in fog computing open their resources, their devices are easily intercepted and attacked because they are accessed through wireless network and present an extensive geographical distribution. In this study, a credible third party was introduced to supervise the behavior of users and protect the security of user cooperation. A fog computing security mechanism based on human nervous system is proposed, and the strategy for a stable system evolution is calculated. The MATLAB simulation results show that the proposed mechanism can reduce the number of attack behaviors effectively and stimulate users to cooperate in application tasks positively.

  2. A security mechanism based on evolutionary game in fog computing

    Directory of Open Access Journals (Sweden)

    Yan Sun

    2018-02-01

    Full Text Available Fog computing is a distributed computing paradigm at the edge of the network and requires cooperation of users and sharing of resources. When users in fog computing open their resources, their devices are easily intercepted and attacked because they are accessed through wireless network and present an extensive geographical distribution. In this study, a credible third party was introduced to supervise the behavior of users and protect the security of user cooperation. A fog computing security mechanism based on human nervous system is proposed, and the strategy for a stable system evolution is calculated. The MATLAB simulation results show that the proposed mechanism can reduce the number of attack behaviors effectively and stimulate users to cooperate in application tasks positively.

  3. An evolutionary framework for studying mechanisms of social behavior.

    Science.gov (United States)

    Hofmann, Hans A; Beery, Annaliese K; Blumstein, Daniel T; Couzin, Iain D; Earley, Ryan L; Hayes, Loren D; Hurd, Peter L; Lacey, Eileen A; Phelps, Steven M; Solomon, Nancy G; Taborsky, Michael; Young, Larry J; Rubenstein, Dustin R

    2014-10-01

    Social interactions are central to most animals and have a fundamental impact upon the phenotype of an individual. Social behavior (social interactions among conspecifics) represents a central challenge to the integration of the functional and mechanistic bases of complex behavior. Traditionally, studies of proximate and ultimate elements of social behavior have been conducted by distinct groups of researchers, with little communication across perceived disciplinary boundaries. However, recent technological advances, coupled with increased recognition of the substantial variation in mechanisms underlying social interactions, should compel investigators from divergent disciplines to pursue more integrative analyses of social behavior. We propose an integrative conceptual framework intended to guide researchers towards a comprehensive understanding of the evolution and maintenance of mechanisms governing variation in sociality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. The evolutionary roots of creativity: mechanisms and motivations.

    Science.gov (United States)

    Wiggins, Geraint A; Tyack, Peter; Scharff, Constance; Rohrmeier, Martin

    2015-03-19

    We consider the evolution of cognition and the emergence of creative behaviour, in relation to vocal communication. We address two key questions: (i) what cognitive and/or social mechanisms have evolved that afford aspects of creativity?; (ii) has natural and/or sexual selection favoured human behaviours considered 'creative'? This entails analysis of 'creativity', an imprecise construct: comparable properties in non-humans differ in magnitude and teleology from generally agreed human creativity. We then address two apparent problems: (i) the difference between merely novel productions and 'creative' ones; (ii) the emergence of creative behaviour in spite of high cost: does it fit the idea that females choose a male who succeeds in spite of a handicap (costly ornament); or that creative males capable of producing a large and complex song repertoire grew up under favourable conditions; or a demonstration of generally beneficial heightened reasoning capacity; or an opportunity to continually reinforce social bonding through changing communication tropes; or something else? We illustrate and support our argument by reference to whale and bird song; these independently evolved biological signal mechanisms objectively share surface properties with human behaviours generally called 'creative'. Studying them may elucidate mechanisms underlying human creativity; we outline a research programme to do so. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  5. The evolutionary roots of creativity: mechanisms and motivations

    Science.gov (United States)

    Wiggins, Geraint A.; Tyack, Peter; Scharff, Constance; Rohrmeier, Martin

    2015-01-01

    We consider the evolution of cognition and the emergence of creative behaviour, in relation to vocal communication. We address two key questions: (i) what cognitive and/or social mechanisms have evolved that afford aspects of creativity?; (ii) has natural and/or sexual selection favoured human behaviours considered ‘creative’? This entails analysis of ‘creativity’, an imprecise construct: comparable properties in non-humans differ in magnitude and teleology from generally agreed human creativity. We then address two apparent problems: (i) the difference between merely novel productions and ‘creative’ ones; (ii) the emergence of creative behaviour in spite of high cost: does it fit the idea that females choose a male who succeeds in spite of a handicap (costly ornament); or that creative males capable of producing a large and complex song repertoire grew up under favourable conditions; or a demonstration of generally beneficial heightened reasoning capacity; or an opportunity to continually reinforce social bonding through changing communication tropes; or something else? We illustrate and support our argument by reference to whale and bird song; these independently evolved biological signal mechanisms objectively share surface properties with human behaviours generally called ‘creative’. Studying them may elucidate mechanisms underlying human creativity; we outline a research programme to do so. PMID:25646522

  6. Evolutionary conservation and neuronal mechanisms of auditory perceptual restoration.

    Science.gov (United States)

    Petkov, Christopher I; Sutter, Mitchell L

    2011-01-01

    Auditory perceptual 'restoration' occurs when the auditory system restores an occluded or masked sound of interest. Behavioral work on auditory restoration in humans began over 50 years ago using it to model a noisy environmental scene with competing sounds. It has become clear that not only humans experience auditory restoration: restoration has been broadly conserved in many species. Behavioral studies in humans and animals provide a necessary foundation to link the insights being obtained from human EEG and fMRI to those from animal neurophysiology. The aggregate of data resulting from multiple approaches across species has begun to clarify the neuronal bases of auditory restoration. Different types of neural responses supporting restoration have been found, supportive of multiple mechanisms working within a species. Yet a general principle has emerged that responses correlated with restoration mimic the response that would have been given to the uninterrupted sound of interest. Using the same technology to study different species will help us to better harness animal models of 'auditory scene analysis' to clarify the conserved neural mechanisms shaping the perceptual organization of sound and to advance strategies to improve hearing in natural environmental settings. © 2010 Elsevier B.V. All rights reserved.

  7. Application of Evolutionary Mechanisms of Enhancers for Development Effective Artificial Intelligence Systems for Providing Data Security

    Directory of Open Access Journals (Sweden)

    M. L. Garanina

    2010-06-01

    Full Text Available This article describes the base approaches of the methods of evolutionary mechanisms (special type of genes — enhancers for parameterizations of AI systems genotype. This method can help in increasing adaptability of AI systems for providing data security.

  8. Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

    Directory of Open Access Journals (Sweden)

    Philippe Julien

    Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

  9. The final checkpoint. Cancer as an adaptive evolutionary mechanism

    Directory of Open Access Journals (Sweden)

    Rumena Petkova

    2016-05-01

    Full Text Available The mechanisms for identification of DNA damage and repair usually manage DNA damage very efficiently. If damaged cells manage to bypass the checkpoints where the integrity of the genome is assessed and the decisions whether to proceed with the cell cycle are made, they may evade the imperative to stop dividing and to die. As a result, cancer may develop. Warding off the potential sequence-altering effects of DNA damage during the life of the individual or the existence span of the species is controlled by a set of larger checkpoints acting on a progressively increasing scale, from systematic removal of damaged cells from the proliferative pool by means of repair of DNA damage/programmed cell death through ageing to, finally, cancer. They serve different purposes and act at different levels of the life cycle, safeguarding the integrity of the genetic backup of the individual, the genetic diversity of the population, and, finally, the survival of the species and of life on Earth. In the light of the theory that cancer is the final checkpoint or the nature's manner to prevent complex organisms from living forever at the expense of genetic stagnation, the eventual failure of modern anti-cancer treatments is only to be expected. Nevertheless, the medicine of today and the near future has enough potential to slow down the progression to terminal cancer so that the life expectancy and the quality of life of cancer-affected individuals may be comparable to those of healthy aged individuals.

  10. Shaping mechanisms of metal specificity in a family of metazoan metallothioneins: evolutionary differentiation of mollusc metallothioneins

    Directory of Open Access Journals (Sweden)

    Atrian Sílvia

    2011-01-01

    Full Text Available Abstract Background The degree of metal binding specificity in metalloproteins such as metallothioneins (MTs can be crucial for their functional accuracy. Unlike most other animal species, pulmonate molluscs possess homometallic MT isoforms loaded with Cu+ or Cd2+. They have, so far, been obtained as native metal-MT complexes from snail tissues, where they are involved in the metabolism of the metal ion species bound to the respective isoform. However, it has not as yet been discerned if their specific metal occupation is the result of a rigid control of metal availability, or isoform expression programming in the hosting tissues or of structural differences of the respective peptides determining the coordinative options for the different metal ions. In this study, the Roman snail (Helix pomatia Cu-loaded and Cd-loaded isoforms (HpCuMT and HpCdMT were used as model molecules in order to elucidate the biochemical and evolutionary mechanisms permitting pulmonate MTs to achieve specificity for their cognate metal ion. Results HpCuMT and HpCdMT were recombinantly synthesized in the presence of Cd2+, Zn2+ or Cu2+ and corresponding metal complexes analysed by electrospray mass spectrometry and circular dichroism (CD and ultra violet-visible (UV-Vis spectrophotometry. Both MT isoforms were only able to form unique, homometallic and stable complexes (Cd6-HpCdMT and Cu12-HpCuMT with their cognate metal ions. Yeast complementation assays demonstrated that the two isoforms assumed metal-specific functions, in agreement with their binding preferences, in heterologous eukaryotic environments. In the snail organism, the functional metal specificity of HpCdMT and HpCuMT was contributed by metal-specific transcription programming and cell-specific expression. Sequence elucidation and phylogenetic analysis of MT isoforms from a number of snail species revealed that they possess an unspecific and two metal-specific MT isoforms, whose metal specificity was

  11. Glucan: mechanisms involved in its radioprotective effect

    International Nuclear Information System (INIS)

    Patchen, M.L.; D'Alesandro, M.M.; Brook, I.; Blakely, W.F.; MacVittie, T.J.

    1987-01-01

    It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested

  12. Evolutionary dynamics of adult stem cells: comparison of random and immortal-strand segregation mechanisms.

    Science.gov (United States)

    Tannenbaum, Emmanuel; Sherley, James L; Shakhnovich, Eugene I

    2005-04-01

    This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell and (2) "immortal DNA strand" co-segregation, for which the stem cell retains the daughter chromosomes with the oldest parent strands. Immortal strand co-segregation is a mechanism, originally proposed by [Cairns Nature (London) 255, 197 (1975)], by which stem cells preserve the integrity of their genomes. For random segregation, we develop an ordered strand pair formulation of the dynamics, analogous to the ordered strand pair formalism developed for quasispecies dynamics involving semiconservative replication with imperfect lesion repair (in this context, lesion repair is taken to mean repair of postreplication base-pair mismatches). Interestingly, a similar formulation is possible with immortal strand co-segregation, despite the fact that this segregation mechanism is age dependent. From our model we are able to mathematically show that, when lesion repair is imperfect, then immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosome segregation. Furthermore, our model allows us to estimate the optimal lesion repair efficiency for preserving an adult stem cell population for a given period of time. For human stem cells, we obtain that mispaired bases still present after replication and cell division should be left untouched, to avoid potentially fixing a mutation in both DNA strands.

  13. Research on Evolutionary Mechanism of Agile Supply Chain Network via Complex Network Theory

    Directory of Open Access Journals (Sweden)

    Nai-Ru Xu

    2016-01-01

    Full Text Available The paper establishes the evolutionary mechanism model of agile supply chain network by means of complex network theory which can be used to describe the growth process of the agile supply chain network and analyze the complexity of the agile supply chain network. After introducing the process and the suitability of taking complex network theory into supply chain network research, the paper applies complex network theory into the agile supply chain network research, analyzes the complexity of agile supply chain network, presents the evolutionary mechanism of agile supply chain network based on complex network theory, and uses Matlab to simulate degree distribution, average path length, clustering coefficient, and node betweenness. Simulation results show that the evolution result displays the scale-free property. It lays the foundations of further research on agile supply chain network based on complex network theory.

  14. Evolutionary History of the Enzymes Involved in the Calvin-Benson Cycle in Euglenids.

    Science.gov (United States)

    Markunas, Chelsea M; Triemer, Richard E

    2016-05-01

    Euglenids are an ancient lineage that may have existed as early as 2 billion years ago. A mere 65 years ago, Melvin Calvin and Andrew A. Benson performed experiments on Euglena gracilis and elucidated the series of reactions by which carbon was fixed and reduced during photosynthesis. However, the evolutionary history of this pathway (Calvin-Benson cycle) in euglenids was more complex than Calvin and Benson could have imagined. The chloroplast present today in euglenophytes arose from a secondary endosymbiosis between a phagotrophic euglenid and a prasinophyte green alga. A long period of evolutionary time existed before this secondary endosymbiotic event took place, which allowed for other endosymbiotic events or gene transfers to occur prior to the establishment of the green chloroplast. This research revealed the evolutionary history of the major enzymes of the Calvin-Benson cycle throughout the euglenid lineage and showed that the majority of genes for Calvin-Benson cycle enzymes shared an ancestry with red algae and/or chromophytes suggesting they may have been transferred to the nucleus prior to the acquisition of the green chloroplast. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

  15. Molecular and Evolutionary Mechanisms of Cuticular Wax for Plant Drought Tolerance

    Directory of Open Access Journals (Sweden)

    Dawei Xue

    2017-04-01

    Full Text Available Cuticular wax, the first protective layer of above ground tissues of many plant species, is a key evolutionary innovation in plants. Cuticular wax safeguards the evolution from certain green algae to flowering plants and the diversification of plant taxa during the eras of dry and adverse terrestrial living conditions and global climate changes. Cuticular wax plays significant roles in plant abiotic and biotic stress tolerance and has been implicated in defense mechanisms against excessive ultraviolet radiation, high temperature, bacterial and fungal pathogens, insects, high salinity, and low temperature. Drought, a major type of abiotic stress, poses huge threats to global food security and health of terrestrial ecosystem by limiting plant growth and crop productivity. The composition, biochemistry, structure, biosynthesis, and transport of plant cuticular wax have been reviewed extensively. However, the molecular and evolutionary mechanisms of cuticular wax in plants in response to drought stress are still lacking. In this review, we focus on potential mechanisms, from evolutionary, molecular, and physiological aspects, that control cuticular wax and its roles in plant drought tolerance. We also raise key research questions and propose important directions to be resolved in the future, leading to potential applications of cuticular wax for water use efficiency in agricultural and environmental sustainability.

  16. An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

    Science.gov (United States)

    Orabona, Guilherme; Morgan, Thomas; Haataja, Ritva; Hallman, Mikko; Puttonen, Hilkka; Menon, Ramkumar; Kuczynski, Edward; Norwitz, Errol; Snegovskikh, Victoria; Palotie, Aarno; Fellman, Vineta; DeFranco, Emily A.; Chaudhari, Bimal P.; McGregor, Tracy L.; McElroy, Jude J.; Oetjens, Matthew T.; Teramo, Kari; Borecki, Ingrid; Fay, Justin; Muglia, Louis

    2011-01-01

    Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition. PMID:21533219

  17. Probing the evolutionary history of epigenetic mechanisms: what can we learn from marine diatoms

    Directory of Open Access Journals (Sweden)

    Achal Rastogi

    2015-07-01

    Full Text Available Recent progress made on epigenetic studies revealed the conservation of epigenetic features in deep diverse branching species including Stramenopiles, plants and animals. This suggests their fundamental role in shaping species genomes across different evolutionary time scales. Diatoms are a highly successful and diverse group of phytoplankton with a fossil record of about 190 million years ago. They are distantly related from other super-groups of Eukaryotes and have retained some of the epigenetic features found in mammals and plants suggesting their ancient origin. Phaeodactylum tricornutum and Thalassiosira pseudonana, pennate and centric diatoms, respectively, emerged as model species to address questions on the evolution of epigenetic phenomena such as what has been lost, retained or has evolved in contemporary species. In the present work, we will discuss how the study of non-model or emerging model organisms, such as diatoms, helps understand the evolutionary history of epigenetic mechanisms with a particular focus on DNA methylation and histone modifications.

  18. Heterogeneous update mechanisms in evolutionary games: Mixing innovative and imitative dynamics

    Science.gov (United States)

    Amaral, Marco Antonio; Javarone, Marco Alberto

    2018-04-01

    Innovation and evolution are two processes of paramount relevance for social and biological systems. In general, the former allows the introduction of elements of novelty, while the latter is responsible for the motion of a system in its phase space. Often, these processes are strongly related, since an innovation can trigger the evolution, and the latter can provide the optimal conditions for the emergence of innovations. Both processes can be studied by using the framework of evolutionary game theory, where evolution constitutes an intrinsic mechanism. At the same time, the concept of innovation requires an opportune mathematical representation. Notably, innovation can be modeled as a strategy, or it can constitute the underlying mechanism that allows agents to change strategy. Here, we analyze the second case, investigating the behavior of a heterogeneous population, composed of imitative and innovative agents. Imitative agents change strategy only by imitating that of their neighbors, whereas innovative ones change strategy without the need for a copying source. The proposed model is analyzed by means of analytical calculations and numerical simulations in different topologies. Remarkably, results indicate that the mixing of mechanisms can be detrimental to cooperation near phase transitions. In those regions, the spatial reciprocity from imitative mechanisms is destroyed by innovative agents, leading to the downfall of cooperation. Our investigation sheds some light on the complex dynamics emerging from the heterogeneity of strategy revision methods, highlighting the role of innovation in evolutionary games.

  19. Learning from evolutionary optimisation: what are toughening mechanisms good for in dentine, a nonrepairing bone tissue?

    Science.gov (United States)

    Zaslansky, Paul; Currey, John D; Fleck, Claudia

    2016-09-12

    The main mass of material found in teeth is dentine, a bone-like tissue, riddled with micron-sized tubules and devoid of living cells. It provides support to the outer wear-resistant layer of enamel, and exhibits toughening mechanisms which contribute to crack resistance. And yet unlike most bone tissues, dentine does not remodel and consequently any accumulated damage does not 'self repair'. Because damage containment followed by tissue replacement is a prime reason for the crack-arresting microstructures found in most bones, the occurrence of toughening mechanisms without the biological capability to repair is puzzling. Here we consider the notion that dentine might be overdesigned for strength, because it has to compensate for the lack of cell-mediated healing mechanisms. Based on our own and on literature-reported observations, including quasistatic and fatigue properties, dentine design principles are discussed in light of the functional conditions under which teeth evolved. We conclude that dentine is only slightly overdesigned for everyday cyclic loading because usual mastication stresses may come close to its endurance strength. The in-built toughening mechanisms constitute an evolutionary benefit because they prevent catastrophic failure during rare overload events, which was probably very advantageous in our hunter gatherer ancestor times. From a bio-inspired perspective, understanding the extent of evolutionary overdesign might be useful for optimising biomimetic structures used for load bearing.

  20. Mitochondrial genome sequencing helps show the evolutionary mechanism of mitochondrial genome formation in Brassica

    Science.gov (United States)

    2011-01-01

    Background Angiosperm mitochondrial genomes are more complex than those of other organisms. Analyses of the mitochondrial genome sequences of at least 11 angiosperm species have showed several common properties; these cannot easily explain, however, how the diverse mitotypes evolved within each genus or species. We analyzed the evolutionary relationships of Brassica mitotypes by sequencing. Results We sequenced the mitotypes of cam (Brassica rapa), ole (B. oleracea), jun (B. juncea), and car (B. carinata) and analyzed them together with two previously sequenced mitotypes of B. napus (pol and nap). The sizes of whole single circular genomes of cam, jun, ole, and car are 219,747 bp, 219,766 bp, 360,271 bp, and 232,241 bp, respectively. The mitochondrial genome of ole is largest as a resulting of the duplication of a 141.8 kb segment. The jun mitotype is the result of an inherited cam mitotype, and pol is also derived from the cam mitotype with evolutionary modifications. Genes with known functions are conserved in all mitotypes, but clear variation in open reading frames (ORFs) with unknown functions among the six mitotypes was observed. Sequence relationship analysis showed that there has been genome compaction and inheritance in the course of Brassica mitotype evolution. Conclusions We have sequenced four Brassica mitotypes, compared six Brassica mitotypes and suggested a mechanism for mitochondrial genome formation in Brassica, including evolutionary events such as inheritance, duplication, rearrangement, genome compaction, and mutation. PMID:21988783

  1. Tools for Accurate and Efficient Analysis of Complex Evolutionary Mechanisms in Microbial Genomes. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Nakhleh, Luay

    2014-03-12

    I proposed to develop computationally efficient tools for accurate detection and reconstruction of microbes' complex evolutionary mechanisms, thus enabling rapid and accurate annotation, analysis and understanding of their genomes. To achieve this goal, I proposed to address three aspects. (1) Mathematical modeling. A major challenge facing the accurate detection of HGT is that of distinguishing between these two events on the one hand and other events that have similar "effects." I proposed to develop a novel mathematical approach for distinguishing among these events. Further, I proposed to develop a set of novel optimization criteria for the evolutionary analysis of microbial genomes in the presence of these complex evolutionary events. (2) Algorithm design. In this aspect of the project, I proposed to develop an array of e cient and accurate algorithms for analyzing microbial genomes based on the formulated optimization criteria. Further, I proposed to test the viability of the criteria and the accuracy of the algorithms in an experimental setting using both synthetic as well as biological data. (3) Software development. I proposed the nal outcome to be a suite of software tools which implements the mathematical models as well as the algorithms developed.

  2. Species-Specific Mechanisms of Neuron Subtype Specification Reveal Evolutionary Plasticity of Amniote Brain Development

    Directory of Open Access Journals (Sweden)

    Tadashi Nomura

    2018-03-01

    Full Text Available Summary: Highly ordered brain architectures in vertebrates consist of multiple neuron subtypes with specific neuronal connections. However, the origin of and evolutionary changes in neuron specification mechanisms remain unclear. Here, we report that regulatory mechanisms of neuron subtype specification are divergent in developing amniote brains. In the mammalian neocortex, the transcription factors (TFs Ctip2 and Satb2 are differentially expressed in layer-specific neurons. In contrast, these TFs are co-localized in reptilian and avian dorsal pallial neurons. Multi-potential progenitors that produce distinct neuronal subtypes commonly exist in the reptilian and avian dorsal pallium, whereas a cis-regulatory element of avian Ctip2 exhibits attenuated transcription suppressive activity. Furthermore, the neuronal subtypes distinguished by these TFs are not tightly associated with conserved neuronal connections among amniotes. Our findings reveal the evolutionary plasticity of regulatory gene functions that contribute to species differences in neuronal heterogeneity and connectivity in developing amniote brains. : Neuronal heterogeneity is essential for assembling intricate neuronal circuits. Nomura et al. find that species-specific transcriptional mechanisms underlie diversities of excitatory neuron subtypes in mammalian and non-mammalian brains. Species differences in neuronal subtypes and connections suggest functional plasticity of regulatory genes for neuronal specification during amniote brain evolution. Keywords: Ctip2, Satb2, multi-potential progenitors, transcriptional regulation, neuronal connectivity

  3. Multiple evolutionary events involved in maintaining homologs of Resistance to Powdery Mildew 8 in Brassica napus

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    Qin Li

    2016-07-01

    Full Text Available The Resistance to Powdery Mildew 8 (RPW8 locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs in Brassica rapa and three in B. oleracea (BoHRs. B. napus (Bn is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs. It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane (EHM encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants.

  4. Multiple Evolutionary Events Involved in Maintaining Homologs of Resistance to Powdery Mildew 8 in Brassica napus.

    Science.gov (United States)

    Li, Qin; Li, Jing; Sun, Jin-Long; Ma, Xian-Feng; Wang, Ting-Ting; Berkey, Robert; Yang, Hui; Niu, Ying-Ze; Fan, Jing; Li, Yan; Xiao, Shunyuan; Wang, Wen-Ming

    2016-01-01

    The Resistance to Powdery Mildew 8 (RPW8) locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs) in Brassica rapa and three in Brassica oleracea (BoHRs). Brassica napus (Bn) is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs). It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here, we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion, and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants.

  5. Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome.

    Science.gov (United States)

    Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Liu, Zhen-Xing; Hao, Le; Ma, Jiang-Yao; Li, Yu-Gu

    2016-02-24

    Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts.

  6. Altered DNA methylation: a secondary mechanism involved in carcinogenesis.

    Science.gov (United States)

    Goodman, Jay I; Watson, Rebecca E

    2002-01-01

    This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?

  7. A study on the fundamental mechanism and the evolutionary driving forces behind aerobic fermentation in yeast.

    Science.gov (United States)

    Hagman, Arne; Piškur, Jure

    2015-01-01

    Baker's yeast Saccharomyces cerevisiae rapidly converts sugars to ethanol and carbon dioxide at both anaerobic and aerobic conditions. The later phenomenon is called Crabtree effect and has been described in two forms, long-term and short-term effect. We have previously studied under fully controlled aerobic conditions forty yeast species for their central carbon metabolism and the presence of long-term Crabtree effect. We have also studied ten steady-state yeast cultures, pulsed them with glucose, and followed the central carbon metabolism and the appearance of ethanol at dynamic conditions. In this paper we analyzed those wet laboratory data to elucidate possible mechanisms that determine the fate of glucose in different yeast species that cover approximately 250 million years of evolutionary history. We determine overflow metabolism to be the fundamental mechanism behind both long- and short-term Crabtree effect, which originated approximately 125-150 million years ago in the Saccharomyces lineage. The "invention" of overflow metabolism was the first step in the evolution of aerobic fermentation in yeast. It provides a general strategy to increase energy production rates, which we show is positively correlated to growth. The "invention" of overflow has also simultaneously enabled rapid glucose consumption in yeast, which is a trait that could have been selected for, to "starve" competitors in nature. We also show that glucose repression of respiration is confined mainly among S. cerevisiae and closely related species that diverged after the whole genome duplication event, less than 100 million years ago. Thus, glucose repression of respiration was apparently "invented" as a second step to further increase overflow and ethanol production, to inhibit growth of other microbes. The driving force behind the initial evolutionary steps was most likely competition with other microbes to faster consume and convert sugar into biomass, in niches that were semi-anaerobic.

  8. A study on the fundamental mechanism and the evolutionary driving forces behind aerobic fermentation in yeast.

    Directory of Open Access Journals (Sweden)

    Arne Hagman

    Full Text Available Baker's yeast Saccharomyces cerevisiae rapidly converts sugars to ethanol and carbon dioxide at both anaerobic and aerobic conditions. The later phenomenon is called Crabtree effect and has been described in two forms, long-term and short-term effect. We have previously studied under fully controlled aerobic conditions forty yeast species for their central carbon metabolism and the presence of long-term Crabtree effect. We have also studied ten steady-state yeast cultures, pulsed them with glucose, and followed the central carbon metabolism and the appearance of ethanol at dynamic conditions. In this paper we analyzed those wet laboratory data to elucidate possible mechanisms that determine the fate of glucose in different yeast species that cover approximately 250 million years of evolutionary history. We determine overflow metabolism to be the fundamental mechanism behind both long- and short-term Crabtree effect, which originated approximately 125-150 million years ago in the Saccharomyces lineage. The "invention" of overflow metabolism was the first step in the evolution of aerobic fermentation in yeast. It provides a general strategy to increase energy production rates, which we show is positively correlated to growth. The "invention" of overflow has also simultaneously enabled rapid glucose consumption in yeast, which is a trait that could have been selected for, to "starve" competitors in nature. We also show that glucose repression of respiration is confined mainly among S. cerevisiae and closely related species that diverged after the whole genome duplication event, less than 100 million years ago. Thus, glucose repression of respiration was apparently "invented" as a second step to further increase overflow and ethanol production, to inhibit growth of other microbes. The driving force behind the initial evolutionary steps was most likely competition with other microbes to faster consume and convert sugar into biomass, in niches that

  9. Interplay between cooperation-enhancing mechanisms in evolutionary games with tag-mediated interactions

    Science.gov (United States)

    Hadzibeganovic, Tarik; Stauffer, Dietrich; Han, Xiao-Pu

    2018-04-01

    Cooperation is fundamental for the long-term survival of biological, social, and technological networks. Previously, mechanisms for the enhancement of cooperation, such as network reciprocity, have largely been studied in isolation and with often inconclusive findings. Here, we present an evolutionary, multiagent-based, and spatially explicit computer model to specifically address the interactive interplay between such mechanisms. We systematically investigate the effects of phenotypic diversity, network structure, and rewards on cooperative behavior emerging in a population of reproducing artificial decision makers playing tag-mediated evolutionary games. Cooperative interactions are rewarded such that both the benefits of recipients and costs of donators are affected by the reward size. The reward size is determined by the number of cooperative acts occurring within a given reward time frame. Our computational experiments reveal that small reward frames promote unconditional cooperation in populations with both low and high diversity, whereas large reward frames lead to cycles of conditional and unconditional strategies at high but not at low diversity. Moreover, an interaction between rewards and spatial structure shows that relative to small reward frames, there is a strong difference between the frequency of conditional cooperators populating rewired versus non-rewired networks when the reward frame is large. Notably, in a less diverse population, the total number of defections is comparable across different network topologies, whereas in more diverse environments defections become more frequent in a regularly structured than in a rewired, small-world network of contacts. Acknowledging the importance of such interaction effects in social dilemmas will have inevitable consequences for the future design of cooperation-enhancing protocols in large-scale, distributed, and decentralized systems such as peer-to-peer networks.

  10. Evolutionary history of callose synthases in terrestrial plants with emphasis on proteins involved in male gametophyte development.

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    Lenka Záveská Drábková

    Full Text Available Callose is a plant-specific polysaccharide (β-1,3-glucan playing an important role in angiosperms in many developmental processes and responses to biotic and abiotic stresses. Callose is synthesised at the plasma membrane of plant cells by callose synthase (CalS and, among others, represents the main polysaccharide in the callose wall surrounding the tetrads of developing microspores and in the growing pollen tube wall. CalS proteins involvement in spore development is a plesiomorphic feature of terrestrial plants, but very little is known about their evolutionary origin and relationships amongst the members of this protein family. We performed thorough comparative analyses of callose synthase family proteins from major plant lineages to determine their evolutionary history across the plant kingdom. A total of 1211 candidate CalS sequences were identified and compared amongst diverse taxonomic groups of plants, from bryophytes to angiosperms. Phylogenetic analyses identified six main clades of CalS proteins and suggested duplications during the evolution of specialised functions. Twelve family members had previously been identified in Arabidopsis thaliana. We focused on five CalS subfamilies directly linked to pollen function and found that proteins expressed in pollen evolved twice. CalS9/10 and CalS11/12 formed well-defined clades, whereas pollen-specific CalS5 was found within subfamilies that mostly did not express in mature pollen vegetative cell, although were found in sperm cells. Expression of five out of seven mature pollen-expressed CalS genes was affected by mutations in bzip transcription factors. Only three subfamilies, CalS5, CalS10, and CalS11, however, formed monophyletic, mostly conserved clades. The pairs CalS9/CalS10, CalS11/CalS12 and CalS3 may have diverged after angiosperms diversified from lycophytes and bryophytes. Our analysis of fully sequenced plant proteins identified new evolutionary lineages of callose synthase

  11. Sex ratio meiotic drive as a plausible evolutionary mechanism for hybrid male sterility.

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    Linbin Zhang

    2015-03-01

    Full Text Available Biological diversity on Earth depends on the multiplication of species or speciation, which is the evolution of reproductive isolation such as hybrid sterility between two new species. An unsolved puzzle is the exact mechanism(s that causes two genomes to diverge from their common ancestor so that some divergent genes no longer function properly in the hybrids. Here we report genetic analyses of divergent genes controlling male fertility and sex ratio in two very young fruitfly species, Drosophila albomicans and D. nasuta. A majority of the genetic divergence for both traits is mapped to the same regions by quantitative trait loci mappings. With introgressions, six major loci are found to contribute to both traits. This genetic colocalization implicates that genes for hybrid male sterility have evolved primarily for controlling sex ratio. We propose that genetic conflicts over sex ratio may operate as a perpetual dynamo for genome divergence. This particular evolutionary mechanism may largely contribute to the rapid evolution of hybrid male sterility and the disproportionate enrichment of its underlying genes on the X chromosome--two patterns widely observed across animals.

  12. Caught in self-interaction: evolutionary and functional mechanisms of protein homooligomerization

    International Nuclear Information System (INIS)

    Hashimoto, Kosuke; Nishi, Hafumi; Bryant, Stephen; Panchenko, Anna R

    2011-01-01

    Many soluble and membrane proteins form homooligomeric complexes in a cell which are responsible for the diversity and specificity of many pathways, may mediate and regulate gene expression, activity of enzymes, ion channels, receptors, and cell adhesion processes. The evolutionary and physical mechanisms of oligomerization are very diverse and its general principles have not yet been formulated. Homooligomeric states may be conserved within certain protein subfamilies and might be important in providing specificity to certain substrates while minimizing interactions with other unwanted partners. Moreover, recent studies have led to a greater awareness that transitions between different oligomeric states may regulate protein activity and provide the switch between different pathways. In this paper we summarize the biological importance of homooligomeric assemblies, physico-chemical properties of their interfaces, experimental and computational methods for their identification and prediction. We particularly focus on homooligomer evolution and describe the mechanisms to develop new specificities through the formation of different homooligomeric complexes. Finally, we discuss the possible role of oligomeric transitions in the regulation of protein activity and compile a set of experimental examples with such regulatory mechanisms

  13. Diversity in viral anti-PKR mechanisms: a remarkable case of evolutionary convergence.

    Directory of Open Access Journals (Sweden)

    Elena Domingo-Gil

    Full Text Available Most viruses express during infection products that prevent or neutralize the effect of the host dsRNA activated protein kinase (PKR. Translation of Sindbis virus (SINV mRNA escapes to PKR activation and eIF2 phosphorylation in infected cells by a mechanism that requires a stem loop structure in viral 26S mRNA termed DLP to initiate translation in the absence of functional eIF2. Unlike the rest of viruses tested, we found that Alphavirus infection allowed a strong PKR activation and eIF2α phosphorylation in vitro and in infected animals so that the presence of DLP structure in mRNA was critical for translation and replication of SINV. Interestingly, infection of MEFs with some viruses that express PKR inhibitors prevented eIF2α phosphorylation after superinfection with SINV, suggesting that viral anti-PKR mechanisms could be exchangeable. Thus, translation of SINV mutant lacking the DLP structure (ΔDLP in 26S mRNA was partially rescued in cells expressing vaccinia virus (VV E3 protein, a known inhibitor of PKR. This case of heterotypic complementation among evolutionary distant viruses confirmed experimentally a remarkable case of convergent evolution in viral anti-PKR mechanisms. Our data reinforce the critical role of PKR in regulating virus-host interaction and reveal the versatility of viruses to find different solutions to solve the same conflict.

  14. Sex ratio meiotic drive as a plausible evolutionary mechanism for hybrid male sterility.

    Science.gov (United States)

    Zhang, Linbin; Sun, Tianai; Woldesellassie, Fitsum; Xiao, Hailian; Tao, Yun

    2015-03-01

    Biological diversity on Earth depends on the multiplication of species or speciation, which is the evolution of reproductive isolation such as hybrid sterility between two new species. An unsolved puzzle is the exact mechanism(s) that causes two genomes to diverge from their common ancestor so that some divergent genes no longer function properly in the hybrids. Here we report genetic analyses of divergent genes controlling male fertility and sex ratio in two very young fruitfly species, Drosophila albomicans and D. nasuta. A majority of the genetic divergence for both traits is mapped to the same regions by quantitative trait loci mappings. With introgressions, six major loci are found to contribute to both traits. This genetic colocalization implicates that genes for hybrid male sterility have evolved primarily for controlling sex ratio. We propose that genetic conflicts over sex ratio may operate as a perpetual dynamo for genome divergence. This particular evolutionary mechanism may largely contribute to the rapid evolution of hybrid male sterility and the disproportionate enrichment of its underlying genes on the X chromosome--two patterns widely observed across animals.

  15. Diversification of defensins and NLRs in Arabidopsis species by different evolutionary mechanisms.

    Science.gov (United States)

    Mondragón-Palomino, Mariana; Stam, Remco; John-Arputharaj, Ajay; Dresselhaus, Thomas

    2017-12-15

    Genes encoding proteins underlying host-pathogen co-evolution and which are selected for new resistance specificities frequently are under positive selection, a process that maintains diversity. Here, we tested the contribution of natural selection, recombination and transcriptional divergence to the evolutionary diversification of the plant defensins superfamily in three Arabidopsis species. The intracellular NOD-like receptor (NLR) family was used for comparison because positive selection has been well documented in its members. Similar to defensins, NLRs are encoded by a large and polymorphic gene family and many of their members are involved in the immune response. Gene trees of Arabidopsis defensins (DEFLs) show a high prevalence of clades containing orthologs. This indicates that their diversity dates back to a common ancestor and species-specific duplications did not significantly contribute to gene family expansion. DEFLs are characterized by a pervasive pattern of neutral evolution with infrequent positive and negative selection as well as recombination. In comparison, most NLR alignment groups are characterized by frequent occurrence of positive selection and recombination in their leucine-rich repeat (LRR) domain as well negative selection in their nucleotide-binding (NB-ARC) domain. While major NLR subgroups are expressed in pistils and leaves both in presence or absence of pathogen infection, the members of DEFL alignment groups are predominantly transcribed in pistils. Furthermore, conserved groups of NLRs and DEFLs are differentially expressed in response to Fusarium graminearum regardless of whether these genes are under positive selection or not. The present analyses of NLRs expands previous studies in Arabidopsis thaliana and highlights contrasting patterns of purifying and diversifying selection affecting different gene regions. DEFL genes show a different evolutionary trend, with fewer recombination events and significantly fewer instances of

  16. Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

    Science.gov (United States)

    Borges, Juliana Pereira; Lessa, Marcos Adriano

    2015-01-01

    Background Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions. PMID:25830711

  17. Evolutionary mechanisms driving the evolution of a large polydnavirus gene family coding for protein tyrosine phosphatases

    Directory of Open Access Journals (Sweden)

    Serbielle Céline

    2012-12-01

    Full Text Available Abstract Background Gene duplications have been proposed to be the main mechanism involved in genome evolution and in acquisition of new functions. Polydnaviruses (PDVs, symbiotic viruses associated with parasitoid wasps, are ideal model systems to study mechanisms of gene duplications given that PDV genomes consist of virulence genes organized into multigene families. In these systems the viral genome is integrated in a wasp chromosome as a provirus and virus particles containing circular double-stranded DNA are injected into the parasitoids’ hosts and are essential for parasitism success. The viral virulence factors, organized in gene families, are required collectively to induce host immune suppression and developmental arrest. The gene family which encodes protein tyrosine phosphatases (PTPs has undergone spectacular expansion in several PDV genomes with up to 42 genes. Results Here, we present strong indications that PTP gene family expansion occurred via classical mechanisms: by duplication of large segments of the chromosomally integrated form of the virus sequences (segmental duplication, by tandem duplications within this form and by dispersed duplications. We also propose a novel duplication mechanism specific to PDVs that involves viral circle reintegration into the wasp genome. The PTP copies produced were shown to undergo conservative evolution along with episodes of adaptive evolution. In particular recently produced copies have undergone positive selection in sites most likely involved in defining substrate selectivity. Conclusion The results provide evidence about the dynamic nature of polydnavirus proviral genomes. Classical and PDV-specific duplication mechanisms have been involved in the production of new gene copies. Selection pressures associated with antagonistic interactions with parasitized hosts have shaped these genes used to manipulate lepidopteran physiology with evidence for positive selection involved in

  18. Evolutionary conserved mechanisms pervade structure and transcriptional modulation of allograft inflammatory factor-1 from sea anemone Anemonia viridis.

    Science.gov (United States)

    Cuttitta, Angela; Ragusa, Maria Antonietta; Costa, Salvatore; Bennici, Carmelo; Colombo, Paolo; Mazzola, Salvatore; Gianguzza, Fabrizio; Nicosia, Aldo

    2017-08-01

    Gene family encoding allograft inflammatory factor-1 (AIF-1) is well conserved among organisms; however, there is limited knowledge in lower organisms. In this study, the first AIF-1 homologue from cnidarians was identified and characterised in the sea anemone Anemonia viridis. The full-length cDNA of AvAIF-1 was of 913 bp with a 5' -untranslated region (UTR) of 148 bp, a 3'-UTR of 315 and an open reading frame (ORF) of 450 bp encoding a polypeptide with149 amino acid residues and predicted molecular weight of about 17 kDa. The predicted protein possesses evolutionary conserved EF hand Ca 2+ binding motifs, post-transcriptional modification sites and a 3D structure which can be superimposed with human members of AIF-1 family. The AvAIF-1 transcript was constitutively expressed in all tested tissues of unchallenged sea anemone, suggesting that AvAIF-1 could serve as a general protective factor under normal physiological conditions. Moreover, we profiled the transcriptional activation of AvAIF-1 after challenges with different abiotic/biotic stresses showing induction by warming conditions, heavy metals exposure and immune stimulation. Thus, mechanisms associated to inflammation and immune challenges up-regulated AvAIF-1 mRNA levels. Our results suggest its involvement in the inflammatory processes and immune response of A. viridis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Long-range seasonal migration in insects: mechanisms, evolutionary drivers and ecological consequences.

    Science.gov (United States)

    Chapman, Jason W; Reynolds, Don R; Wilson, Kenneth

    2015-03-01

    Myriad tiny insect species take to the air to engage in windborne migration, but entomology also has its 'charismatic megafauna' of butterflies, large moths, dragonflies and locusts. The spectacular migrations of large day-flying insects have long fascinated humankind, and since the advent of radar entomology much has been revealed about high-altitude night-time insect migrations. Over the last decade, there have been significant advances in insect migration research, which we review here. In particular, we highlight: (1) notable improvements in our understanding of lepidopteran navigation strategies, including the hitherto unsuspected capabilities of high-altitude migrants to select favourable winds and orientate adaptively, (2) progress in unravelling the neuronal mechanisms underlying sun compass orientation and in identifying the genetic complex underpinning key traits associated with migration behaviour and performance in the monarch butterfly, and (3) improvements in our knowledge of the multifaceted interactions between disease agents and insect migrants, in terms of direct effects on migration success and pathogen spread, and indirect effects on the evolution of migratory systems. We conclude by highlighting the progress that can be made through inter-phyla comparisons, and identify future research areas that will enhance our understanding of insect migration strategies within an eco-evolutionary perspective. © 2015 John Wiley & Sons Ltd/CNRS.

  20. Part E: Evolutionary Computation

    DEFF Research Database (Denmark)

    2015-01-01

    of Computational Intelligence. First, comprehensive surveys of genetic algorithms, genetic programming, evolution strategies, parallel evolutionary algorithms are presented, which are readable and constructive so that a large audience might find them useful and – to some extent – ready to use. Some more general...... kinds of evolutionary algorithms, have been prudently analyzed. This analysis was followed by a thorough analysis of various issues involved in stochastic local search algorithms. An interesting survey of various technological and industrial applications in mechanical engineering and design has been...... topics like the estimation of distribution algorithms, indicator-based selection, etc., are also discussed. An important problem, from a theoretical and practical point of view, of learning classifier systems is presented in depth. Multiobjective evolutionary algorithms, which constitute one of the most...

  1. Numerical and Experimental Study of Mechanisms Involved in Boiling Histotripsy.

    Science.gov (United States)

    Pahk, Ki Joo; Gélat, Pierre; Sinden, David; Dhar, Dipok Kumar; Saffari, Nader

    2017-12-01

    The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves. To investigate the mechanisms involved in boiling histotripsy, a high-speed camera with a passive cavitation detection system was used to observe the dynamics of bubbles produced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0-MHz high-intensity focused ultrasound (HIFU) transducer. We observed that boiling bubbles were generated in a localized heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole-shaped lesion. A simplified numerical model describing the scattering of the incident ultrasound wave by a vapor bubble was developed to help interpret the experimental observations. Together with the numerical results, these observations suggest that the overall size of a lesion induced by boiling histotripsy is dependent on the sizes of (i) the heated region at the HIFU focus and (ii) the backscattered acoustic field by the original vapor bubble. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  2. Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas

    Directory of Open Access Journals (Sweden)

    Gisselsson David

    2007-09-01

    Full Text Available Abstract Background Neuroblastoma (NB is the most common extracranial solid tumour of childhood. Several genomic imbalances correlate to prognosis in NB, with structural rearrangements, including gene amplification, in a near-diploid setting typically signifying high-risk tumours and numerical changes in a near-triploid setting signifying low-risk tumours. Little is known about the temporal sequence in which these imbalances occur during the carcinogenic process. Methods We have reconstructed the appearance of cytogenetic imbalances in 270 NBs by first grouping tumours and imbalances through principal component analysis and then using the number of imbalances in each tumour as an indicator of evolutionary progression. Results Tumours clustered in four sub-groups, dominated respectively by (1 gene amplification in double minute chromosomes and few other aberrations, (2 gene amplification and loss of 1p sequences, (3 loss of 1p and other structural aberrations including gain of 17q, and (4 whole-chromosome gains and losses. Temporal analysis showed that the structural changes in groups 1–3 were acquired in a step-wise fashion, with loss of 1p sequences and the emergence of double minute chromosomes as the earliest cytogenetic events. In contrast, the gains and losses of whole chromosomes in group 4 occurred through multiple simultaneous events leading to a near-triploid chromosome number. Conclusion The finding of different temporal patterns for the acquisition of genomic imbalances in high-risk and low-risk NBs lends strong support to the hypothesis that these tumours are biologically diverse entities, evolving through distinct genetic mechanisms.

  3. Quantum-Mechanical Calculations on Molecular Substructures Involved in Nanosystems

    Directory of Open Access Journals (Sweden)

    Beata Szefler

    2014-09-01

    Full Text Available In this review article, four ideas are discussed: (a aromaticity of fullerenes patched with flowers of 6-and 8-membered rings, optimized at the HF and DFT levels of theory, in terms of HOMA and NICS criteria; (b polybenzene networks, from construction to energetic and vibrational spectra computations; (c quantum-mechanical calculations on the repeat units of various P-type crystal networks and (d construction and stability evaluation, at DFTB level of theory, of some exotic allotropes of diamond D5, involved in hyper-graphenes. The overall conclusion was that several of the yet hypothetical molecular nanostructures herein described are serious candidates to the status of real molecules.

  4. Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

  5. Investigations into the involvement of NMDA mechanisms in recognition memory.

    Science.gov (United States)

    Warburton, E Clea; Barker, Gareth R I; Brown, Malcom W

    2013-11-01

    This review will focus on evidence showing that NMDA receptor neurotransmission is critical for synaptic plasticity processes within brain regions known to be necessary for the formation of object recognition memories. The aim will be to provide evidence concerning NMDA mechanisms related to recognition memory processes and show that recognition memory for objects, places or associations between objects and places depends on NMDA neurotransmission within the perirhinal cortex, temporal association cortex medial prefrontal cortex and hippocampus. Administration of the NMDA antagonist AP5, selectively into each of these brain regions has revealed that the extent of the involvement NMDA receptors appears dependent on the type of information required to solve the recognition memory task; thus NMDA receptors in the perirhinal cortex are crucial for the encoding of long-term recognition memory for objects, and object-in-place associations, but not for short-term recognition memory or for retrieval. In contrast the hippocampus and medial prefrontal cortex are required for both long-term and short-term recognition memory for places or associations between objects and places, or for recognition memory tasks that have a temporal component. Such studies have therefore confirmed that the multiple brain regions make distinct contributions to recognition memory but in addition that more than one synaptic plasticity process must be involved. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Research on Information Sharing Mechanism of Network Organization Based on Evolutionary Game

    Science.gov (United States)

    Wang, Lin; Liu, Gaozhi

    2018-02-01

    This article first elaborates the concept and effect of network organization, and the ability to share information is analyzed, secondly introduces the evolutionary game theory, network organization for information sharing all kinds of limitations, establishes the evolutionary game model, analyzes the dynamic evolution of network organization of information sharing, through reasoning and evolution. The network information sharing by the initial state and two sides of the game payoff matrix of excess profits and information is the information sharing of cost and risk sharing are the influence of network organization node information sharing decision.

  7. Mechanisms and factors involved in hip injuries during frontal crashes.

    Science.gov (United States)

    Yoganandan, N; Pintar, F A; Gennarelli, T A; Maltese, M R; Eppinger, R H

    2001-11-01

    This study was conducted to collect data and gain insights relative to the mechanisms and factors involved in hip injuries during frontal crashes and to study the tolerance of hip injuries from this type of loading. Unembalmed human cadavers were seated on a standard automotive seat (reinforced) and subjected to knee impact test to each lower extremity. Varying combinations of flexion and adduction/abduction were used for initial alignment conditions and pre-positioning. Accelerometers were fixed to the iliac wings and twelfth thoracic vertebral spinous process. A 23.4-kg padded pendulum impacted the knee at velocities ranging from 4.3 to 7.6 m/s. The impacting direction was along the anteroposterior axis, i.e., the global X-axis, in the body-fixed coordinate system. A load cell on the front of the pendulum recorded the impact force. Peak impact forces ranged from 2,450 to 10,950 N. The rate of loading ranged from 123 to 7,664 N/msec. The impulse values ranged from 12.4 to 31.9 Nsec. Injuries were not apparent in three tests. Eight tests resulted in trauma. Fractures involving the pelvis including the acetabulum and proximal femur occurred in five out of the eight tests, and distal femoral bone fracture occurred in one test. These results underscore the importance of leg pre-positioning and the orientation of the impacting axis to produce specific types of trauma to the pelvic region of the lower extremity.

  8. The genome sequence of the North-European cucumber (Cucumis sativus L.) unravels evolutionary adaptation mechanisms in plants.

    Science.gov (United States)

    Wóycicki, Rafał; Witkowicz, Justyna; Gawroński, Piotr; Dąbrowska, Joanna; Lomsadze, Alexandre; Pawełkowicz, Magdalena; Siedlecka, Ewa; Yagi, Kohei; Pląder, Wojciech; Seroczyńska, Anna; Śmiech, Mieczysław; Gutman, Wojciech; Niemirowicz-Szczytt, Katarzyna; Bartoszewski, Grzegorz; Tagashira, Norikazu; Hoshi, Yoshikazu; Borodovsky, Mark; Karpiński, Stanisław; Malepszy, Stefan; Przybecki, Zbigniew

    2011-01-01

    Cucumber (Cucumis sativus L.), a widely cultivated crop, has originated from Eastern Himalayas and secondary domestication regions includes highly divergent climate conditions e.g. temperate and subtropical. We wanted to uncover adaptive genome differences between the cucumber cultivars and what sort of evolutionary molecular mechanisms regulate genetic adaptation of plants to different ecosystems and organism biodiversity. Here we present the draft genome sequence of the Cucumis sativus genome of the North-European Borszczagowski cultivar (line B10) and comparative genomics studies with the known genomes of: C. sativus (Chinese cultivar--Chinese Long (line 9930)), Arabidopsis thaliana, Populus trichocarpa and Oryza sativa. Cucumber genomes show extensive chromosomal rearrangements, distinct differences in quantity of the particular genes (e.g. involved in photosynthesis, respiration, sugar metabolism, chlorophyll degradation, regulation of gene expression, photooxidative stress tolerance, higher non-optimal temperatures tolerance and ammonium ion assimilation) as well as in distributions of abscisic acid-, dehydration- and ethylene-responsive cis-regulatory elements (CREs) in promoters of orthologous group of genes, which lead to the specific adaptation features. Abscisic acid treatment of non-acclimated Arabidopsis and C. sativus seedlings induced moderate freezing tolerance in Arabidopsis but not in C. sativus. This experiment together with analysis of abscisic acid-specific CRE distributions give a clue why C. sativus is much more susceptible to moderate freezing stresses than A. thaliana. Comparative analysis of all the five genomes showed that, each species and/or cultivars has a specific profile of CRE content in promoters of orthologous genes. Our results constitute the substantial and original resource for the basic and applied research on environmental adaptations of plants, which could facilitate creation of new crops with improved growth and yield in

  9. Transcriptome analysis deciphers evolutionary mechanisms underlying genetic differentiation between coastal and offshore anchovy populations in the Bay of Biscay

    KAUST Repository

    Montes, Iratxe; Zarraonaindia, Iratxe; Iriondo, Mikel; Grant, W. Stewart; Manzano, Carmen; Cotano, Unai; Conklin, Darrell; Irigoien, Xabier; Estonba, Andone

    2016-01-01

    Morphometry and otolith microchemistry point to the existence of two populations of the European anchovy (Engraulis encrasicolus) in the Bay of Biscay: one in open seawaters, and a yet unidentified population in coastal waters. To test this hypothesis, we assembled a large number of samples from the region, including 587 juveniles and spawning adults from offshore and coastal waters, and 264 fish from other locations covering most of the species’ European range. These samples were genotyped for 456 exonic SNPs that provide a robust way to decipher adaptive processes in these populations. Two genetically differentiated populations of anchovy inhabit the Bay of Biscay with different population dynamics: (1) a large offshore population associated with marine waters included in the wide-shelf group, and (2) a coastal metapopulation adapted to estuarine environments in the Bay of Biscay and North Sea included in the narrow-shelf group. Transcriptome analysis identified neutral and adaptive evolutionary processes underlying differentiation between these populations. Reduced gene flow between offshore and coastal populations in the Bay of Biscay appears to result from divergence between two previously isolated gene pools adapted to contrasting habitats and now in secondary contact. Eleven molecular markers appear to mark divergent selection between the ecotypes, and a majority of these markers are associated with salinity variability. Ecotype differences at two outlier genes, TSSK6 and basigin, may hinder gamete compatibility between the ecotypes and reinforce reproductive isolation. Additionally, possible convergent evolution between offshore and coastal populations in the Bay of Biscay has been detected for the syntaxin1B-otoferlin gene system, which is involved in the control of larval buoyancy. Further study of exonic markers opens the possibility of understanding the mechanisms of adaptive divergence between European anchovy populations. © 2016, Springer

  10. Transcriptome analysis deciphers evolutionary mechanisms underlying genetic differentiation between coastal and offshore anchovy populations in the Bay of Biscay

    KAUST Repository

    Montes, Iratxe

    2016-09-13

    Morphometry and otolith microchemistry point to the existence of two populations of the European anchovy (Engraulis encrasicolus) in the Bay of Biscay: one in open seawaters, and a yet unidentified population in coastal waters. To test this hypothesis, we assembled a large number of samples from the region, including 587 juveniles and spawning adults from offshore and coastal waters, and 264 fish from other locations covering most of the species’ European range. These samples were genotyped for 456 exonic SNPs that provide a robust way to decipher adaptive processes in these populations. Two genetically differentiated populations of anchovy inhabit the Bay of Biscay with different population dynamics: (1) a large offshore population associated with marine waters included in the wide-shelf group, and (2) a coastal metapopulation adapted to estuarine environments in the Bay of Biscay and North Sea included in the narrow-shelf group. Transcriptome analysis identified neutral and adaptive evolutionary processes underlying differentiation between these populations. Reduced gene flow between offshore and coastal populations in the Bay of Biscay appears to result from divergence between two previously isolated gene pools adapted to contrasting habitats and now in secondary contact. Eleven molecular markers appear to mark divergent selection between the ecotypes, and a majority of these markers are associated with salinity variability. Ecotype differences at two outlier genes, TSSK6 and basigin, may hinder gamete compatibility between the ecotypes and reinforce reproductive isolation. Additionally, possible convergent evolution between offshore and coastal populations in the Bay of Biscay has been detected for the syntaxin1B-otoferlin gene system, which is involved in the control of larval buoyancy. Further study of exonic markers opens the possibility of understanding the mechanisms of adaptive divergence between European anchovy populations. © 2016, Springer

  11. Diapause and quiescence: dormancy mechanisms that contribute to the geographical expansion of mosquitoes and their evolutionary success.

    Science.gov (United States)

    Diniz, Diego Felipe Araujo; de Albuquerque, Cleide Maria Ribeiro; Oliva, Luciana Oliveira; de Melo-Santos, Maria Alice Varjal; Ayres, Constância Flávia Junqueira

    2017-06-26

    Mosquitoes are insects belonging to the order Diptera and family Culicidae. They are distributed worldwide and include approximately 3500 species, of which about 300 have medical and veterinary importance. The evolutionary success of mosquitoes, in both tropical and temperate regions, is due to the various survival strategies these insects have developed throughout their life histories. Of the many adaptive mechanisms, diapause and quiescence, two different types of dormancy, likely contribute to the establishment, maintenance and spread of natural mosquito populations. This review seeks to objectively and coherently describe the terms diapause and quiescence, which can be confused in the literature because the phenotypic effects of these mechanisms are often similar.

  12. Connecting proximate mechanisms and evolutionary patterns: pituitary gland size and mammalian life history.

    Science.gov (United States)

    Kamilar, J M; Tecot, S R

    2015-11-01

    At the proximate level, hormones are known to play a critical role in influencing the life history of mammals, including humans. The pituitary gland is directly responsible for producing several hormones, including those related to growth and reproduction. Although we have a basic understanding of how hormones affect life history characteristics, we still have little knowledge of this relationship in an evolutionary context. We used data from 129 mammal species representing 14 orders to investigate the relationship between pituitary gland size and life history variation. Because pituitary gland size should be related to hormone production and action, we predicted that species with relatively large pituitaries should be associated with fast life histories, especially increased foetal and post-natal growth rates. Phylogenetic analyses revealed that total pituitary size and the size of the anterior lobe of the pituitary significantly predicted a life history axis that was correlated with several traits including body mass, and foetal and post-natal growth rates. Additional models directly examining the association between relative pituitary size and growth rates produced concordant results. We also found that relative pituitary size variation across mammals was best explained by an Ornstein-Uhlenbeck model of evolution, suggesting an important role of stabilizing selection. Our results support the idea that the size of the pituitary is linked to life history variation through evolutionary time. This pattern is likely due to mediating hormone levels but additional work is needed. We suggest that future investigations incorporating endocrine gland size may be critical for understanding life history evolution. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  13. The Evolutionary History Of The White-Rayed Species Of Melampodium (Asteraceae) Involved Multiple Cycles Of Hybridization And Polyploidization1

    Science.gov (United States)

    Rebernig, Carolin A.; Weiss-Schneeweiss, Hanna; Blöch, Cordula; Turner, Barbara; Stuessy, Tod F.; Obermayer, Renate; Villaseñor, Jose L.; Schneeweiss, Gerald M.

    2014-01-01

    Premise of the study Polyploidy plays an important role in race differentiation and eventually speciation. Underlying mechanisms include chromosomal and genomic changes facilitating reproductive isolation and/or stabilization of hybrids. A prerequisite for studying these processes is a sound knowledge on the origin of polyploids. A well-suited group for studying polyploid evolution consists of the three species of Melampodium ser. Leucantha (Asteraceae): M. argophyllum, M. cinereum, and M. leucanthum. Methods The origin of polyploids was inferred using network and tree-based phylogenetic analyses of several plastid and nuclear DNA sequences and of fingerprint data (AFLP). Genome evolution was assessed via genome size measurements, karyotype analysis, and in situ hybridization of ribosomal DNA. Key results Tetraploid cytotypes of the phylogenetically distinct M. cinereum and M. leucanthum had, compared to the diploid cytotypes, doubled genome sizes and no evidence of gross chromosomal rearrangements. Hexaploid M. argophyllum constituted a separate lineage with limited intermixing with the other species, except in analyses from nuclear ITS. Its genome size was lower than expected if M. cinereum and/or M. leucanthum were involved in its origin, and no chromosomal rearrangements were evident. Conclusions Polyploids in M. cinereum and M. leucanthum are of recent autopolyploid origin in line with the lack of significant genomic changes. Hexaploid M. argophyllum also appears to be of autopolyploid origin against the previous hypothesis of an allopolyploid origin involving the other two species, but some gene flow with the other species in early phases of differentiation cannot be excluded. PMID:22645096

  14. Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

    Science.gov (United States)

    Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

    1999-11-01

    The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

  15. Evolutionary dynamics of adult stem cells: Comparison of random and immortal strand segregation mechanisms

    OpenAIRE

    Tannenbaum, Emmanuel; Sherley, James L.; Shakhnovich, Eugene I.

    2004-01-01

    This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) Random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell. (2) ``Immortal DNA strand'' co-segregation, for which the stem cell reta...

  16. Overview of in-vessel retention concept involving level of passivity: with application to evolutionary pressurized water reactor design

    International Nuclear Information System (INIS)

    Ghyym, Seong H.

    1998-01-01

    In this work, one strategy of severe accident management, the applicability of the in-vessel retention (IVR) concept, which has been incorporated in passive type reactor designs, to evolutionary type reactor designs, is examined with emphasis on the method of external reactor vessel cooling (ERVC) to realize the IVR concept in view of two aspects: for the regulatory aspect, it is addressed in the context of the resolution of the issue of corium coolability; for the technical one, the reliance on and the effectiveness of the IVR concept are mentioned. Additionally, for the ERVC method to be better applied to designs of the evolutionary type reactor, the conditions to be met are pointed out in view of the technical aspect. Concerning the issue of corium coolability/quenchability, based on results of the review, plausible alternative strategies are proposed. According to the decision maker's risk behavior, these would help materialize the conceptual design for evolutionary type reactors, especially Korea Next Generation Reactors (KNGRs), which have been developing at the Korea Electric Power Research Institute (KEPRI): (A1) Strategy 1A: strategy based on the global approach using the reliance on the wet cavity method; (A2) Strategy 1B: strategy based on the combined approach using both the reliance on the wet cavity method and the counter-measures for preserving containment integrity; (A3) Strategy 2A: strategy based on the global approach to the reliance on the ERVC method; (A4) Strategy 2B: strategy based on the balanced approach using both the reliance on the ERVC method and the countermeasures for preserving containment integrity. Finally, in application to an advanced pressurized water reactor (PWR) design, several recommendations are made in focusing on both monitoring the status of approaches and preparing countermeasures in regard to the regulatory and the technical aspects

  17. 3D computational mechanics elucidate the evolutionary implications of orbit position and size diversity of early amphibians.

    Directory of Open Access Journals (Sweden)

    Jordi Marcé-Nogué

    Full Text Available For the first time in vertebrate palaeontology, the potential of joining Finite Element Analysis (FEA and Parametrical Analysis (PA is used to shed new light on two different cranial parameters from the orbits to evaluate their biomechanical role and evolutionary patterns. The early tetrapod group of Stereospondyls, one of the largest groups of Temnospondyls is used as a case study because its orbits position and size vary hugely within the members of this group. An adult skull of Edingerella madagascariensis was analysed using two different cases of boundary and loading conditions in order to quantify stress and deformation response under a bilateral bite and during skull raising. Firstly, the variation of the original geometry of its orbits was introduced in the models producing new FEA results, allowing the exploration of the ecomorphology, feeding strategy and evolutionary patterns of these top predators. Secondly, the quantitative results were analysed in order to check if the orbit size and position were correlated with different stress patterns. These results revealed that in most of the cases the stress distribution is not affected by changes in the size and position of the orbit. This finding supports the high mechanical plasticity of this group during the Triassic period. The absence of mechanical constraints regarding the orbit probably promoted the ecomorphological diversity acknowledged for this group, as well as its ecological niche differentiation in the terrestrial Triassic ecosystems in clades as lydekkerinids, trematosaurs, capitosaurs or metoposaurs.

  18. 3D Computational Mechanics Elucidate the Evolutionary Implications of Orbit Position and Size Diversity of Early Amphibians

    Science.gov (United States)

    Marcé-Nogué, Jordi; Fortuny, Josep; De Esteban-Trivigno, Soledad; Sánchez, Montserrat; Gil, Lluís; Galobart, Àngel

    2015-01-01

    For the first time in vertebrate palaeontology, the potential of joining Finite Element Analysis (FEA) and Parametrical Analysis (PA) is used to shed new light on two different cranial parameters from the orbits to evaluate their biomechanical role and evolutionary patterns. The early tetrapod group of Stereospondyls, one of the largest groups of Temnospondyls is used as a case study because its orbits position and size vary hugely within the members of this group. An adult skull of Edingerella madagascariensis was analysed using two different cases of boundary and loading conditions in order to quantify stress and deformation response under a bilateral bite and during skull raising. Firstly, the variation of the original geometry of its orbits was introduced in the models producing new FEA results, allowing the exploration of the ecomorphology, feeding strategy and evolutionary patterns of these top predators. Secondly, the quantitative results were analysed in order to check if the orbit size and position were correlated with different stress patterns. These results revealed that in most of the cases the stress distribution is not affected by changes in the size and position of the orbit. This finding supports the high mechanical plasticity of this group during the Triassic period. The absence of mechanical constraints regarding the orbit probably promoted the ecomorphological diversity acknowledged for this group, as well as its ecological niche differentiation in the terrestrial Triassic ecosystems in clades as lydekkerinids, trematosaurs, capitosaurs or metoposaurs. PMID:26107295

  19. Mechanisms Involved in Nematode Control by Endophytic Fungi.

    Science.gov (United States)

    Schouten, Alexander

    2016-08-04

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood but most likely multifactorial. This knowledge gap obstructs the progress regarding the development of endophytes or endophyte-derived constituents into biocontrol agents. In part, this may be caused by the fact that endophytic fungi form a rather heterogeneous group. By combining the knowledge of the currently characterized antagonistic endophytic fungi and their effects on nematode behavior and biology with the knowledge of microbial competition and induced plant defenses, the various mechanisms by which this nematode antagonism operates or may operate are discussed. Now that new technologies are becoming available and more accessible, the currently unresolved mechanisms can be studied in greater detail than ever before.

  20. Exploring the evolutionary mechanism of complex supply chain systems using evolving hypergraphs

    Science.gov (United States)

    Suo, Qi; Guo, Jin-Li; Sun, Shiwei; Liu, Han

    2018-01-01

    A new evolutionary model is proposed to describe the characteristics and evolution pattern of supply chain systems using evolving hypergraphs, in which nodes represent enterprise entities while hyperedges represent the relationships among diverse trades. The nodes arrive at the system in accordance with a Poisson process, with the evolving process incorporating the addition of new nodes, linking of old nodes, and rewiring of links. Grounded in the Poisson process theory and continuum theory, the stationary average hyperdegree distribution is shown to follow a shifted power law (SPL), and the theoretical predictions are consistent with the results of numerical simulations. Testing the impact of parameters on the model yields a positive correlation between hyperdegree and degree. The model also uncovers macro characteristics of the relationships among enterprises due to the microscopic interactions among individuals.

  1. Mechanisms Involved in Nematode Control by Endophytic Fungi

    NARCIS (Netherlands)

    Schouten, Sander

    2016-01-01

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood

  2. Biological pathways and genetic mechanisms involved in social functioning.

    Science.gov (United States)

    Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

    2013-08-01

    To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

  3. Involvement of thiol-based mechanisms in plant development.

    Science.gov (United States)

    Rouhier, Nicolas; Cerveau, Delphine; Couturier, Jérémy; Reichheld, Jean-Philippe; Rey, Pascal

    2015-08-01

    Increasing knowledge has been recently gained regarding the redox regulation of plant developmental stages. The current state of knowledge concerning the involvement of glutathione, glutaredoxins and thioredoxins in plant development is reviewed. The control of the thiol redox status is mainly ensured by glutathione (GSH), a cysteine-containing tripeptide and by reductases sharing redox-active cysteines, glutaredoxins (GRXs) and thioredoxins (TRXs). Indeed, thiol groups present in many regulatory proteins and metabolic enzymes are prone to oxidation, ultimately leading to post-translational modifications such as disulfide bond formation or glutathionylation. This review focuses on the involvement of GSH, GRXs and TRXs in plant development. Recent studies showed that the proper functioning of root and shoot apical meristems depends on glutathione content and redox status, which regulate, among others, cell cycle and hormone-related processes. A critical role of GRXs in the formation of floral organs has been uncovered, likely through the redox regulation of TGA transcription factor activity. TRXs fulfill many functions in plant development via the regulation of embryo formation, the control of cell-to-cell communication, the mobilization of seed reserves, the biogenesis of chloroplastic structures, the metabolism of carbon and the maintenance of cell redox homeostasis. This review also highlights the tight relationships between thiols, hormones and carbon metabolism, allowing a proper development of plants in relation with the varying environment and the energy availability. GSH, GRXs and TRXs play key roles during the whole plant developmental cycle via their antioxidant functions and the redox-regulation of signaling pathways. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Comparative mitochondrial genome analysis reveals the evolutionary rearrangement mechanism in Brassica.

    Science.gov (United States)

    Yang, J; Liu, G; Zhao, N; Chen, S; Liu, D; Ma, W; Hu, Z; Zhang, M

    2016-05-01

    The genus Brassica has many species that are important for oil, vegetable and other food products. Three mitochondrial genome types (mitotype) originated from its common ancestor. In this paper, a B. nigra mitochondrial main circle genome with 232,407 bp was generated through de novo assembly. Synteny analysis showed that the mitochondrial genomes of B. rapa and B. oleracea had a better syntenic relationship than B. nigra. Principal components analysis and development of a phylogenetic tree indicated maternal ancestors of three allotetraploid species in Us triangle of Brassica. Diversified mitotypes were found in allotetraploid B. napus, in which napus-type B. napus was derived from B. oleracea, while polima-type B. napus was inherited from B. rapa. In addition, the mitochondrial genome of napus-type B. napus was closer to botrytis-type than capitata-type B. oleracea. The sub-stoichiometric shifting of several mitochondrial genes suggested that mitochondrial genome rearrangement underwent evolutionary selection during domestication and/or plant breeding. Our findings clarify the role of diploid species in the maternal origin of allotetraploid species in Brassica and suggest the possibility of breeding selection of the mitochondrial genome. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  5. Kinetics and mechanisms of reactions involving small aromatic reactive intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Lin, M.C. [Emory Univ., Atlanta, GA (United States)

    1993-12-01

    Small aromatic radicals such as C{sub 6}H{sub 5}, C{sub 6}H{sub 5}O and C{sub 6}H{sub 4} are key prototype species of their homologs. C{sub 6}H{sub 5} and its oxidation product, C{sub 6}H{sub 5}O are believed to be important intermediates which play a pivotal role in hydrocarbon combustion, particularly with regard to soot formation. Despite their fundamental importance, experimental data on the reaction mechanisms and reactivities of these species are very limited. For C{sub 6}H{sub 5}, most kinetic data except its reactions with NO and NO{sub 2}, were obtained by relative rate measurements. For C{sub 6}H{sub 5}O, the authors have earlier measured its fragmentation reaction producing C{sub 5}H{sub 5} + CO in shock waves. For C{sub 6}H{sub 4}, the only rate constant measured in the gas phase is its recombination rate at room temperature. The authors have proposed to investigate systematically the kinetics and mechanisms of this important class of molecules using two parallel laser diagnostic techniques--laser resonance absorption (LRA) and resonance enhanced multiphoton ionization mass spectrometry (REMPI/MS). In the past two years, study has been focused on the development of a new multipass adsorption technique--the {open_quotes}cavity-ring-down{close_quotes} technique for kinetic applications. The preliminary results of this study appear to be quite good and the sensitivity of the technique is at least comparable to that of the laser-induced fluorescence method.

  6. Molecular mechanisms involved in the production of chromosomal aberrations. I

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Obe, G.

    1978-01-01

    Chinese hamster ovary cells (CHO) were X-irradiated in G2 stage of the cell cycle and immediately treated, in the presence of inactivated Sendai virus, with Neurospora endonuclease (E.C. 3.1.4.), an enzyme which is specific for cleaving single-stranded DNA. With this treatment, the frequencies of all types of chromosome aberrations increased when compared to X-irradiated controls. These results are interpreted as due to the conversion of some of the X-ray induced single-stranded DNA breaks into double-strand breaks by this enzyme. Similar enhancement due to this enzyme was found following treatment with methyl methanesulfonate (MMS) and bleomycin, but not following UV and mitomycin C. Addition of Micrococcus endonuclease and Neurospora endonuclease to the cells did not alter the frequencies of aberrations induced by UV. The introduction of enzymes with specific DNA-repair function offers possibilities to probe into the molecular events involved in the formation of structural chromosome aberrations induced by different classes of physical and chemical mutagens. (Auth.)

  7. The Potential Mechanism of ZFX Involvement in the Cell Growth

    Directory of Open Access Journals (Sweden)

    Mahboube Ganji arjenaki

    2016-04-01

    Full Text Available Background:The zinc-finger X linked (ZFX gene encodes a transcription factor that acts as a regulator of self-renewal of stem cells. Due to the role of ZFX in cell growth, understanding ZFX protein-protein interactions helps to clarify its proper biological functions in signaling pathways. The aim of this study is to define ZFX protein-protein interactions and the role of ZFX in cell growth. Materials and Methods: The PIPs output includes three interacting proteins with ZFX: eukaryotic translation initiation factor 3 subunit I(EIF3I, eukaryotic translation initiation factor 3 subunit G(EIF3G and protein nuclear pore and COPII coat complex component homolog isoform 3 (SEC13L1. Results: As a cargo and transmembrane protein interacting with Sec13,eIF3I and eIF3G, ZFX mediates cargo sorting in COPII vesicles at ER exit sites. While traveling to cis-Golgi, eIF3I is phosphorylated by the mechanistic target of rapamycin (mTOR. Proteins transport by COPI vesicles to the nucleusouter site layer containing SEC13 via the contribution of microtubules. EIF3G and eIF3I interact with coatomer protein complex subunit beta 2 (COPB2 that helps to enclose ZFX in COPI vesicle. ZFX and eIF3G enter nucleolus where activation of transcription from pre rDNA genes occurs. Conclusion:We proposed a model in which ZFX is involved in cell growth by promoting the transcription of rDNA genes.

  8. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  9. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Solhaug, A.; Vines, L.L.; Ivanova, L.; Spilsberg, B.; Holme, J.A.; Pestka, J.; Collins, A.; Eriksen, G.S.

    2012-01-01

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15–30 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 μM for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  10. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    International Nuclear Information System (INIS)

    Kawano, Michinao; Ariyoshi, Wataru; Iwanaga, Kenjiro; Okinaga, Toshinori; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro; Nishihara, Tatsuji

    2011-01-01

    Research highlights: → In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. → MG63 cells were incubated with BMP-2 and HA for various time periods. → Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. → HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and nuclear translocation

  11. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Michinao [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Iwanaga, Kenjiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Habu, Manabu [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Yoshioka, Izumi [Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan)

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  12. Fault bars in bird feathers: mechanisms, and ecological and evolutionary causes and consequences.

    Science.gov (United States)

    Jovani, Roger; Rohwer, Sievert

    2017-05-01

    Fault bars are narrow malformations in feathers oriented almost perpendicular to the rachis where the feather vein and even the rachis may break. Breaks in the barbs and barbules result in small pieces of the feather vein being lost, while breaks in the rachis result in loss of the distal portion of the feather. Here, we provide a comprehensive review of 74 papers on fault bar formation in hopes of providing a clearer approach to their study. First, we review the evidence that the propensity to develop fault bars is modified by natural selection. Given that fault bars persist in the face of survival costs, we conclude that they must be an unfortunate consequence of some alternative adaptation that outweighs the fitness costs of fault bars. Second, we summarize evidence that the development of fault bars is triggered by psychological stress such as that of handling or predation attempts, and that they persist because the sudden contractions of the muscles in the feather follicle that control fright moults also causes the development of fault bars in growing feathers. Third, we review external and physiological (e.g. corticosterone) agents that may affect the likelihood that an acute stress will result in a growing feather exhibiting a fault bar. These modifying factors have often been treated as fundamental causes in the earlier literature on fault bars. Fourth, we then use this classification to propose a tentative model where fault bars of different severity (from light to severe) are the outcome of the interaction between the propensity to produce fault bars (which differs between species, individuals and feather follicles within individuals) and the intensity of the perturbation. This model helps to explain contradictory results in the literature, to identify gaps in our knowledge, and to suggest further studies. Lastly, we discuss ways in which better understanding of fault bars can inform us about other aspects of avian evolutionary ecology, such as the

  13. Mechanisms of symbiont-conferred protection against natural enemies: an ecological and evolutionary framework.

    Science.gov (United States)

    Gerardo, Nicole M; Parker, Benjamin J

    2014-10-01

    Many vertically-transmitted microbial symbionts protect their insect hosts from natural enemies, including host-targeted pathogens and parasites, and those vectored by insects to other hosts. Protection is often achieved through production of inhibiting toxins, which is not surprising given that toxin production mediates competition in many environments. Classical models of macroecological interactions, however, demonstrate that interspecific competition can be less direct, and recent research indicates that symbiont-protection can be mediated through exploitation of limiting resources, and through activation of host immune mechanisms that then suppress natural enemies. Available data, though limited, suggest that effects of symbionts on vectored pathogens and parasites, as compared to those that are host-targeted, are more likely to result from symbiont activation of the host immune system. We discuss these different mechanisms in light of their potential impact on the evolution of host physiological processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Co-Evolutionary Mechanisms of Emotional Bursts in Online Social Dynamics and Networks

    Directory of Open Access Journals (Sweden)

    Bosiljka Tadić

    2013-11-01

    Full Text Available Collective emotional behavior of users is frequently observed on various Web portals; however, its complexity and the role of emotions in the acting mechanisms are still not thoroughly understood. In this work, using the empirical data and agent-based modeling, a parallel analysis is performed of two archetypal systems—Blogs and Internet-Relayed-Chats—both of which maintain self-organized dynamics but not the same communication rules and time scales. The emphasis is on quantifying the collective emotions by means of fractal analysis of the underlying processes as well as topology of social networks, which arise and co-evolve in these stochastic processes. The results reveal that two distinct mechanisms, which are based on different use of emotions (an emotion is characterized by two components, arousal and valence, are intrinsically associated with two classes of emergent social graphs. Their hallmarks are the evolution of communities in accordance with the excess of the negative emotions on popular Blogs, on one side, and smooth spreading of the Bot’s emotional impact over the entire hierarchical network of chats, on the other. Another emphasis of this work is on the understanding of nonextensivity of the emotion dynamics; it was found that, in its own way, each mechanism leads to a reduced phase space of the emotion components when the collective dynamics takes place. That a non-additive entropy describes emotion dynamics, is further confirmed by computing the q-generalized Kolmogorov-Sinai entropy rate in the empirical data of chats as well as in the simulations of interacting emotional agents and Bots.

  15. Locomotor loading mechanics in the hindlimbs of tegu lizards (Tupinambis merianae): comparative and evolutionary implications.

    Science.gov (United States)

    Sheffield, K Megan; Butcher, Michael T; Shugart, S Katherine; Gander, Jennifer C; Blob, Richard W

    2011-08-01

    Skeletal elements are usually able to withstand several times their usual load before they yield, and this ratio is known as the bone's safety factor. Limited studies on amphibians and non-avian reptiles have shown that they have much higher limb bone safety factors than birds and mammals. It has been hypothesized that this difference is related to the difference in posture between upright birds and mammals and sprawling ectotherms; however, limb bone loading data from a wider range of sprawling species are needed in order to determine whether the higher safety factors seen in amphibians and non-avian reptiles are ancestral or derived conditions. Tegus (family Teiidae) are an ideal lineage with which to expand sampling of limb bone loading mechanics for sprawling taxa, particularly for lizards, because they are from a different clade than previously sampled iguanas and exhibit different foraging and locomotor habits (actively foraging carnivore versus burst-activity herbivore). We evaluated the mechanics of locomotor loading for the femur of the Argentine black and white tegu (Tupinambus merianae) using three-dimensional measurements of the ground reaction force and hindlimb kinematics, in vivo bone strains and femoral mechanical properties. Peak bending stresses experienced by the femur were low (tensile: 10.4 ± 1.1 MPa; compressive: -17.4 ± 0.9 MPa) and comparable to those in other reptiles, with moderate shear stresses and strains also present. Analyses of peak femoral stresses and strains led to estimated safety factor ranges of 8.8-18.6 in bending and 7.8-17.5 in torsion, both substantially higher than typical for birds and mammals but similar to other sprawling tetrapods. These results broaden the range of reptilian and amphibian taxa in which high femoral safety factors have been evaluated and further indicate a trend for the independent evolution of lower limb bone safety factors in endothermic taxa.

  16. Molecular phylogeny and intricate evolutionary history of the three isofunctional enzymes involved in the oxidation of protoporphyrinogen IX.

    Science.gov (United States)

    Kobayashi, Koichi; Masuda, Tatsuru; Tajima, Naoyuki; Wada, Hajime; Sato, Naoki

    2014-08-01

    Tetrapyrroles such as heme and chlorophyll are essential for biological processes, including oxygenation, respiration, and photosynthesis. In the tetrapyrrole biosynthesis pathway, protoporphyrinogen IX oxidase (Protox) catalyzes the formation of protoporphyrin IX, the last common intermediate for the biosynthesis of heme and chlorophyll. Three nonhomologous isofunctional enzymes, HemG, HemJ, and HemY, for Protox have been identified. To reveal the distribution and evolution of the three Protox enzymes, we identified homologs of each along with other heme biosynthetic enzymes by whole-genome clustering across three domains of life. Most organisms possess only one of the three Protox types, with some exceptions. Detailed phylogenetic analysis revealed that HemG is mostly limited to γ-Proteobacteria whereas HemJ may have originated within α-Proteobacteria and transferred to other Proteobacteria and Cyanobacteria. In contrast, HemY is ubiquitous in prokaryotes and is the only Protox in eukaryotes, so this type may be the ancestral Protox. Land plants have a unique HemY homolog that is also shared by Chloroflexus species, in addition to the main HemY homolog originating from Cyanobacteria. Meanwhile, organisms missing any Protox can be classified into two groups; those lacking most heme synthetic genes, which necessarily depend on external heme supply, and those lacking only genes involved in the conversion of uroporphyrinogen III into heme, which would use a precorrin2-dependent alternative pathway. However, hemN encoding coproporphyrinogen IX oxidase was frequently found in organisms lacking Protox enzyme, which suggests a unique role of this gene other than in heme biosynthesis. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Universal effect of dynamical reinforcement learning mechanism in spatial evolutionary games

    International Nuclear Information System (INIS)

    Zhang, Hai-Feng; Wu, Zhi-Xi; Wang, Bing-Hong

    2012-01-01

    One of the prototypical mechanisms in understanding the ubiquitous cooperation in social dilemma situations is the win–stay, lose–shift rule. In this work, a generalized win–stay, lose–shift learning model—a reinforcement learning model with dynamic aspiration level—is proposed to describe how humans adapt their social behaviors based on their social experiences. In the model, the players incorporate the information of the outcomes in previous rounds with time-dependent aspiration payoffs to regulate the probability of choosing cooperation. By investigating such a reinforcement learning rule in the spatial prisoner's dilemma game and public goods game, a most noteworthy viewpoint is that moderate greediness (i.e. moderate aspiration level) favors best the development and organization of collective cooperation. The generality of this observation is tested against different regulation strengths and different types of network of interaction as well. We also make comparisons with two recently proposed models to highlight the importance of the mechanism of adaptive aspiration level in supporting cooperation in structured populations

  18. Evolutionary pattern, operation mechanism and policy orientation of low carbon economy development

    Directory of Open Access Journals (Sweden)

    X. Dou

    2016-10-01

    Full Text Available The essence of low carbon economy development is a continuous evolution and innovation process of socio-economic system from traditional high carbon economy to new sustainable green low carbon economy to achieve a sustainable dynamic balance and benign interactive development of various elements between society, economy and natural ecosystem. At the current stage, China’s socio-economy is showing the feature of "three high" (high energy consumption, high emissions and high pollution. In this case, quickly to promote the development of green low carbon economy is necessary and urgent. This research indicates that, low carbon economy development is achieved by micro-economic agents such as households, businesses and social intermediary organizations through Government’s guidance and the role of market mechanism. In low carbon economy development, the state (government is a leader and markets are core, while economic agents (e.g., households, businesses and social intermediary organizations are basis. For this reason, it is necessary to build an effective cleaner development and incentive-compatible policy system oriented to end-users.

  19. Reassessing Domain Architecture Evolution of Metazoan Proteins: The Contribution of Different Evolutionary Mechanisms

    Directory of Open Access Journals (Sweden)

    Laszlo Patthy

    2011-08-01

    Full Text Available In the accompanying papers we have shown that sequence errors of public databases and confusion of paralogs and epaktologs (proteins that are related only through the independent acquisition of the same domain types significantly distort the picture that emerges from comparison of the domain architecture (DA of multidomain Metazoan proteins since they introduce a strong bias in favor of terminal over internal DA change. The issue of whether terminal or internal DA changes occur with greater probability has very important implications for the DA evolution of multidomain proteins since gene fusion can add domains only at terminal positions, whereas domain-shuffling is capable of inserting domains both at internal and terminal positions. As a corollary, overestimation of terminal DA changes may be misinterpreted as evidence for a dominant role of gene fusion in DA evolution. In this manuscript we show that in several recent studies of DA evolution of Metazoa the authors used databases that are significantly contaminated with incomplete, abnormal and mispredicted sequences (e.g., UniProtKB/TrEMBL, EnsEMBL and/or the authors failed to separate paralogs and epaktologs, explaining why these studies concluded that the major mechanism for gains of new domains in metazoan proteins is gene fusion. In contrast with the latter conclusion, our studies on high quality orthologous and paralogous Swiss-Prot sequences confirm that shuffling of mobile domains had a major role in the evolution of multidomain proteins of Metazoa and especially those formed in early vertebrates.

  20. Evolutionary mechanisms that generate morphology and neural-circuit diversity of the cerebellum.

    Science.gov (United States)

    Hibi, Masahiko; Matsuda, Koji; Takeuchi, Miki; Shimizu, Takashi; Murakami, Yasunori

    2017-05-01

    The cerebellum is derived from the dorsal part of the anterior-most hindbrain. The vertebrate cerebellum contains glutamatergic granule cells (GCs) and gamma-aminobutyric acid (GABA)ergic Purkinje cells (PCs). These cerebellar neurons are generated from neuronal progenitors or neural stem cells by mechanisms that are conserved among vertebrates. However, vertebrate cerebella are widely diverse with respect to their gross morphology and neural circuits. The cerebellum of cyclostomes, the basal vertebrates, has a negligible structure. Cartilaginous fishes have a cerebellum containing GCs, PCs, and deep cerebellar nuclei (DCNs), which include projection neurons. Ray-finned fish lack DCNs but have projection neurons termed eurydendroid cells (ECs) in the vicinity of the PCs. Among ray-finned fishes, the cerebellum of teleost zebrafish has a simple lobular structure, whereas that of weakly electric mormyrid fish is large and foliated. Amniotes, which include mammals, independently evolved a large, foliated cerebellum, which contains massive numbers of GCs and has functional connections with the dorsal telencephalon (neocortex). Recent studies of cyclostomes and cartilaginous fish suggest that the genetic program for cerebellum development was already encoded in the genome of ancestral vertebrates. In this review, we discuss how alterations of the genetic and cellular programs generated diversity of the cerebellum during evolution. © 2017 Japanese Society of Developmental Biologists.

  1. [Possible evolutionary mechanisms of 'culture' in animals: The hypothesis of distributed social learning].

    Science.gov (United States)

    Reznikova, Zh I; Panteleeva, S N

    2015-01-01

    There is a plethora of works on the origin and genesis of behavioral traditions in different animal species. Nevertheless, it still remains unclear as for which factors facilitate and which factors hinder the spreading those forms of behavior that are new for a population. Here, we present an analytical review on the topic, considering also the results of studies on 'culture' in animals and analyzing contradictions that arise when attempting to clarify the ethological mechanisms of cultural succession. The hypothesis of 'distributed social learning' is formulated, meaning that for spreading of complex behavioral stereotypes in a population the presence of few carriers of consistent stereotypes is enough under the condition that the rest of animals carry incomplete genetic programmes that start up these stereotypes. Existence of 'dormant' fragments of such programmes determines an inborn predisposition of their bearer to perform a certain sequence of acts. To complete the consistent stereotype, the simplest forms of social learning ('social alleviation') turn to be enough. The hypothesis is examined at the behavioral level and supported by experimental data obtained when studying the scenarios of hunting behavior development in ants Myrmica rubra L. It makes possible to explain the spreading of behavioral models in animal communities in a simpler way than cultural succession.

  2. Reproductive bribing and policing as evolutionary mechanisms for the suppression of within-group selfishness.

    Science.gov (United States)

    Reeve, H K; Keller, L

    1997-07-01

    We show that a new, simple, and robust general mechanism for the social suppression of within-group selfishness follows from Hamilton's rule applied in a multilevel selection approach to asymmetrical, two-person groups: If it pays a group member to behave selfishly (i.e., increase its share of the group's reproduction, at the expense of group productivity), then its partner will virtually always be favored to provide a reproductive "bribe" sufficient to remove the incentive for the selfish behavior. The magnitude of the bribe will vary directly with the number of offspring (or other close kin) potentially gained by the selfish individual and inversely with both the relatedness r between the interactants and the loss in group productivity because of selfishness. This bribe principle greatly extends the scope for cooperation within groups. Reproductive bribing is more likely to be favored over social policing for dominants rather than subordinates and as intragroup relatedness increases. Finally, analysis of the difference between the group optimum for an individual's behavior and the individual's inclusive fitness optimum reveals a paradoxical feedback loop by which bribing and policing, while nullifying particular selfish acts, automatically widen the separation of individual and group optima for other behaviors (i.e., resolution of one conflict intensifies others).

  3. Hormones and phenotypic plasticity in an ecological context: linking physiological mechanisms to evolutionary processes.

    Science.gov (United States)

    Lema, Sean C

    2014-11-01

    Hormones are chemical signaling molecules that regulate patterns of cellular physiology and gene expression underlying phenotypic traits. Hormone-signaling pathways respond to an organism's external environment to mediate developmental stage-specific malleability in phenotypes, so that environmental variation experienced at different stages of development has distinct effects on an organism's phenotype. Studies of hormone-signaling are therefore playing a central role in efforts to understand how plastic phenotypic responses to environmental variation are generated during development. But, how do adaptive, hormonally mediated phenotypes evolve if the individual signaling components (hormones, conversion enzymes, membrane transporters, and receptors) that comprise any hormone-signaling pathway show expressional flexibility in response to environmental variation? What relevance do these components hold as molecular targets for selection to couple or decouple correlated hormonally mediated traits? This article explores how studying the endocrine underpinnings of phenotypic plasticity in an ecologically relevant context can provide insights into these, and other, crucial questions into the role of phenotypic plasticity in evolution, including how plasticity itself evolves. These issues are discussed in the light of investigations into how thyroid hormones mediate morphological plasticity in Death Valley's clade of pupfishes (Cyprinodon spp.). Findings from this work with pupfish illustrate that the study of hormone-signaling from an ecological perspective can reveal how phenotypic plasticity contributes to the generation of phenotypic novelty, as well as how physiological mechanisms developmentally link an organism's phenotype to its environmental experiences. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  4. Remembering the evolutionary Freud.

    Science.gov (United States)

    Young, Allan

    2006-03-01

    Throughout his career as a writer, Sigmund Freud maintained an interest in the evolutionary origins of the human mind and its neurotic and psychotic disorders. In common with many writers then and now, he believed that the evolutionary past is conserved in the mind and the brain. Today the "evolutionary Freud" is nearly forgotten. Even among Freudians, he is regarded to be a red herring, relevant only to the extent that he diverts attention from the enduring achievements of the authentic Freud. There are three ways to explain these attitudes. First, the evolutionary Freud's key work is the "Overview of the Transference Neurosis" (1915). But it was published at an inopportune moment, forty years after the author's death, during the so-called "Freud wars." Second, Freud eventually lost interest in the "Overview" and the prospect of a comprehensive evolutionary theory of psychopathology. The publication of The Ego and the Id (1923), introducing Freud's structural theory of the psyche, marked the point of no return. Finally, Freud's evolutionary theory is simply not credible. It is based on just-so stories and a thoroughly discredited evolutionary mechanism, Lamarckian use-inheritance. Explanations one and two are probably correct but also uninteresting. Explanation number three assumes that there is a fundamental difference between Freud's evolutionary narratives (not credible) and the evolutionary accounts of psychopathology that currently circulate in psychiatry and mainstream journals (credible). The assumption is mistaken but worth investigating.

  5. Functional and Evolutionary Characterization of a UDP-Xylose Synthase Gene from the Plant Pathogen Xylella fastidiosa, Involved in the Synthesis of Bacterial Lipopolysaccharide.

    Science.gov (United States)

    Alencar, Valquíria Campos; Jabes, Daniela Leite; Menegidio, Fabiano Bezerra; Sassaki, Guilherme Lanzi; de Souza, Lucas Rodrigo; Puzer, Luciano; Meneghetti, Maria Cecília Zorél; Lima, Marcelo Andrade; Tersariol, Ivarne Luis Dos Santos; de Oliveira, Regina Costa; Nunes, Luiz R

    2017-02-07

    Xylella fastidiosa is a plant-infecting bacillus, responsible for many important crop diseases, such as Pierce's disease of vineyards, citrus variegated chlorosis, and coffee leaf scorch (CLS), among others. Recent genomic comparisons involving two CLS-related strains, belonging to X. fastidiosa subsp. pauca, revealed that one of them carries a frameshift mutation that inactivates a gene encoding an oxidoreductase of the short-chain dehydrogenase/reductase (SDR) superfamily, which may play important roles in determining structural variations in bacterial glycans and glycoconjugates. However, the exact nature of this SDR has been a matter of controversy, as different annotations of X. fastidiosa genomes have implicated it in distinct reactions. To confirm the nature of this mutated SDR, a comparative analysis was initially performed, suggesting that it belongs to a subgroup of SDR decarboxylases, representing a UDP-xylose synthase (Uxs). Functional assays, using a recombinant derivative of this enzyme, confirmed its nature as XfUxs, and carbohydrate composition analyses, performed with lipopolysaccharide (LPS) molecules obtained from different strains, indicate that inactivation of the X. fastidiosa uxs gene affects the LPS structure among CLS-related X. fastidiosa strains. Finally, a comparative sequence analysis suggests that this mutation is likely to result in a morphological and evolutionary hallmark that differentiates two subgroups of CLS-related strains, which may influence interactions between these bacteria and their plant and/or insect hosts.

  6. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    International Nuclear Information System (INIS)

    Kaneuji, Takeshi; Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro; Takahashi, Tetsu; Nishihara, Tatsuji

    2011-01-01

    Highlights: → Effect of compressive force on osteoblasts were examined. → Compressive force induced OPG expression and suppressed osteoclastogenesis. → This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm 2 ) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-κB ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of IκBα, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca 2+ pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca 2+ pathway.

  7. Mechanism(s) involved in opioid drug abuse modulation of HAND.

    Science.gov (United States)

    Dutta, Raini; Roy, Sabita

    2012-07-01

    Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.

  8. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kaneuji, Takeshi [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Takahashi, Tetsu [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan)

    2011-04-29

    Highlights: {yields} Effect of compressive force on osteoblasts were examined. {yields} Compressive force induced OPG expression and suppressed osteoclastogenesis. {yields} This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm{sup 2}) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-{kappa}B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I{kappa}B{alpha}, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca{sup 2+} pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt

  9. Evolutionary Nephrology.

    Science.gov (United States)

    Chevalier, Robert L

    2017-05-01

    Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as "maladaptive." In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic) adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or evolutionary tradeoffs. Evolutionary adaptation to a terrestrial environment resulted in a vulnerable energy-consuming renal tubule and a hypoxic, hyperosmolar microenvironment. Natural selection favors successful energy investment strategy: energy is allocated to maintenance of nephron integrity through reproductive years, but this declines with increasing senescence after ~40 years of age. Risk factors for chronic kidney disease include restricted fetal growth or preterm birth (life history tradeoff resulting in fewer nephrons), evolutionary selection for APOL1 mutations (that provide resistance to trypanosome infection, a tradeoff), and modern life experience (Western diet mismatch leading to diabetes and hypertension). Current advances in genomics, epigenetics, and developmental biology have revealed proximate causes of kidney disease, but attempts to slow kidney disease remain elusive. Evolutionary medicine provides a complementary approach by addressing ultimate causes of kidney disease. Marked variation in nephron number at birth, nephron heterogeneity, and changing susceptibility to kidney injury throughout life history are the result of evolutionary processes. Combined application of molecular genetics, evolutionary developmental biology (evo-devo), developmental programming and life history theory may yield new strategies for prevention and treatment of chronic kidney disease.

  10. Constructive anthropomorphism: a functional evolutionary approach to the study of human-like cognitive mechanisms in animals.

    Science.gov (United States)

    Arbilly, Michal; Lotem, Arnon

    2017-10-25

    Anthropomorphism, the attribution of human cognitive processes and emotional states to animals, is commonly viewed as non-scientific and potentially misleading. This is mainly because apparent similarity to humans can usually be explained by alternative, simpler mechanisms in animals, and because there is no explanatory power in analogies to human phenomena when these phenomena are not well understood. Yet, because it is also difficult to preclude real similarity and continuity in the evolution of humans' and animals' cognitive abilities, it may not be productive to completely ignore our understanding of human behaviour when thinking about animals. Here we propose that in applying a functional approach to the evolution of cognitive mechanisms, human cognition may be used to broaden our theoretical thinking and to generate testable hypotheses. Our goal is not to 'elevate' animals, but rather to find the minimal set of mechanistic principles that may explain 'advanced' cognitive abilities in humans, and consider under what conditions these mechanisms were likely to enhance fitness and to evolve in animals. We illustrate this approach, from relatively simple emotional states, to more advanced mechanisms, involved in planning and decision-making, episodic memory, metacognition, theory of mind, and consciousness. © 2017 The Author(s).

  11. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    OpenAIRE

    Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

    2017-01-01

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

  12. Mechanisms involved in the transport of mercuric ions in target tissues

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.

    2016-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells. PMID:27422290

  13. Evidence for the involvement of MC4 receptors in the central mechanisms of opioid antinociception

    NARCIS (Netherlands)

    Starowicz, Katarzyna

    2005-01-01

    The data described in this thesis extend general knowledge of the involvement of the MC4 receptor in mechanisms of analgesia. The following aspects outlined below constitute novel information. Firstly, the MC4R localization in the DRG is demonstrated. The MC4 receptor was assumed to exist

  14. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    Science.gov (United States)

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  15. Hierarchy of mechanisms involved in generating Na/K-ATPase polarity in MDCK epithelial cells

    NARCIS (Netherlands)

    Mays, R.W.; Siemers, K.A.; Fritz, B.A.; Lowe, A.W.; van Meer, G.; Nelson, W.J.

    1995-01-01

    We have studied mechanisms involved in generating a polarized distribution of Na/K-ATPase in the basal-lateral membrane of two clones of MDCK II cells. Both clones exhibit polarized distributions of marker proteins of the apical and basal-lateral membranes, including Na/K-ATPase, at steady state.

  16. The evolutionary implications of epigenetic inheritance.

    Science.gov (United States)

    Jablonka, Eva

    2017-10-06

    The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

  17. Evolutionary Nephrology

    Directory of Open Access Journals (Sweden)

    Robert L. Chevalier

    2017-05-01

    Full Text Available Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as “maladaptive.” In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or from evolutionary tradeoffs. Evolutionary adaptation to a terrestrial environment resulted in a vulnerable energy-consuming renal tubule and a hypoxic, hyperosmolar microenvironment. Natural selection favors successful energy investment strategy: energy is allocated to maintenance of nephron integrity through reproductive years, but this declines with increasing senescence after ∼40 years of age. Risk factors for chronic kidney disease include restricted fetal growth or preterm birth (life history tradeoff resulting in fewer nephrons, evolutionary selection for APOL1 mutations (which provide resistance to trypanosome infection, a tradeoff, and modern life experience (Western diet mismatch leading to diabetes and hypertension. Current advances in genomics, epigenetics, and developmental biology have revealed proximate causes of kidney disease, but attempts to slow kidney disease remain elusive. Evolutionary medicine provides a complementary approach by addressing ultimate causes of kidney disease. Marked variation in nephron number at birth, nephron heterogeneity, and changing susceptibility to kidney injury throughout the life history are the result of evolutionary processes. Combined application of molecular genetics, evolutionary developmental biology (evo-devo, developmental programming, and life history theory may yield new strategies for prevention and treatment of chronic kidney disease.

  18. Regulation of number and size of digits by posterior Hox genes: a dose-dependent mechanism with potential evolutionary implications.

    Science.gov (United States)

    Zákány, J; Fromental-Ramain, C; Warot, X; Duboule, D

    1997-12-09

    The proper development of digits, in tetrapods, requires the activity of several genes of the HoxA and HoxD homeobox gene complexes. By using a variety of loss-of-function alleles involving the five Hox genes that have been described to affect digit patterning, we report here that the group 11, 12, and 13 genes control both the size and number of murine digits in a dose-dependent fashion, rather than through a Hox code involving differential qualitative functions. A similar dose-response is observed in the morphogenesis of the penian bone, the baculum, which further suggests that digits and external genitalia share this genetic control mechanism. A progressive reduction in the dose of Hox gene products led first to ectrodactyly, then to olygodactyly and adactyly. Interestingly, this transition between the pentadactyl to the adactyl formula went through a step of polydactyly. We propose that in the distal appendage of polydactylous short-digited ancestral tetrapods, such as Acanthostega, the HoxA complex was predominantly active. Subsequent recruitment of the HoxD complex contributed to both reductions in digit number and increase in digit length. Thus, transition through a polydactylous limb before reaching and stabilizing the pentadactyl pattern may have relied, at least in part, on asynchronous and independent changes in the regulation of HoxA and HoxD gene complexes.

  19. Education on invasive mechanical ventilation involving intensive care nurses: a systematic review.

    Science.gov (United States)

    Guilhermino, Michelle C; Inder, Kerry J; Sundin, Deborah

    2018-03-26

    Intensive care unit nurses are critical for managing mechanical ventilation. Continuing education is essential in building and maintaining nurses' knowledge and skills, potentially improving patient outcomes. The aim of this study was to determine whether continuing education programmes on invasive mechanical ventilation involving intensive care unit nurses are effective in improving patient outcomes. Five electronic databases were searched from 2001 to 2016 using keywords such as mechanical ventilation, nursing and education. Inclusion criteria were invasive mechanical ventilation continuing education programmes that involved nurses and measured patient outcomes. Primary outcomes were intensive care unit mortality and in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay, length of intubation, failed weaning trials, re-intubation incidence, ventilation-associated pneumonia rate and lung-protective ventilator strategies. Studies were excluded if they excluded nurses, patients were ventilated for less than 24 h, the education content focused on protocol implementation or oral care exclusively or the outcomes were participant satisfaction. Quality was assessed by two reviewers using an education intervention critical appraisal worksheet and a risk of bias assessment tool. Data were extracted independently by two reviewers and analysed narratively due to heterogeneity. Twelve studies met the inclusion criteria for full review: 11 pre- and post-intervention observational and 1 quasi-experimental design. Studies reported statistically significant reductions in hospital length of stay, length of intubation, ventilator-associated pneumonia rates, failed weaning trials and improvements in lung-protective ventilation compliance. Non-statistically significant results were reported for in-hospital and intensive care unit mortality, re-intubation and intensive care unit length of stay. Limited evidence of the effectiveness of

  20. Evolutionary thinking

    Science.gov (United States)

    Hunt, Tam

    2014-01-01

    Evolution as an idea has a lengthy history, even though the idea of evolution is generally associated with Darwin today. Rebecca Stott provides an engaging and thoughtful overview of this history of evolutionary thinking in her 2013 book, Darwin's Ghosts: The Secret History of Evolution. Since Darwin, the debate over evolution—both how it takes place and, in a long war of words with religiously-oriented thinkers, whether it takes place—has been sustained and heated. A growing share of this debate is now devoted to examining how evolutionary thinking affects areas outside of biology. How do our lives change when we recognize that all is in flux? What can we learn about life more generally if we study change instead of stasis? Carter Phipps’ book, Evolutionaries: Unlocking the Spiritual and Cultural Potential of Science's Greatest Idea, delves deep into this relatively new development. Phipps generally takes as a given the validity of the Modern Synthesis of evolutionary biology. His story takes us into, as the subtitle suggests, the spiritual and cultural implications of evolutionary thinking. Can religion and evolution be reconciled? Can evolutionary thinking lead to a new type of spirituality? Is our culture already being changed in ways that we don't realize by evolutionary thinking? These are all important questions and Phipps book is a great introduction to this discussion. Phipps is an author, journalist, and contributor to the emerging “integral” or “evolutionary” cultural movement that combines the insights of Integral Philosophy, evolutionary science, developmental psychology, and the social sciences. He has served as the Executive Editor of EnlightenNext magazine (no longer published) and more recently is the co-founder of the Institute for Cultural Evolution, a public policy think tank addressing the cultural roots of America's political challenges. What follows is an email interview with Phipps. PMID:26478766

  1. Evolutionary Demography

    DEFF Research Database (Denmark)

    Levitis, Daniel

    2015-01-01

    of biological and cultural evolution. Demographic variation within and among human populations is influenced by our biology, and therefore by natural selection and our evolutionary background. Demographic methods are necessary for studying populations of other species, and for quantifying evolutionary fitness......Demography is the quantitative study of population processes, while evolution is a population process that influences all aspects of biological organisms, including their demography. Demographic traits common to all human populations are the products of biological evolution or the interaction...

  2. The mechanisms involved at the cell level; Les mecanismes mis en jeu au niveau cellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Leblanc, G.; Pourcher, Th.; Perron, B. [Nice Univ., Dir. des Sciences du Vivant, Dept. de Biologie Joliot-Curie, 06 (France); Guillain, F. [CEA Grenoble, Dir. des Sciences du Vivant, 38 (France); Quemeneur, E. [CEA Marcoule, Dir. des Sciences du Vivant, 30 (France); Fritsch, P. [CEA Bruyeres le Chatel, Dir. des Sciences du Vivant, 91 (France)

    2003-07-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

  3. Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.

    Science.gov (United States)

    Kozyrev, S A; Nikitin, V P

    2013-03-01

    We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.

  4. Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

    OpenAIRE

    Wan, Ruiqian; Weigand, Letitia A.; Bateman, Ryan; Griffioen, Kathleen; Mendelowitz, David; Mattson, Mark P.

    2014-01-01

    Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haplo...

  5. Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis)

    Science.gov (United States)

    FUNK, W. CHRIS; LOVICH, ROBERT E.; HOHENLOHE, PAUL A.; HOFMAN, COURTNEY A.; MORRISON, SCOTT A.; SILLETT, T. SCOTT; GHALAMBOR, CAMERON K.; MALDONADO, JESUS E.; RICK, TORBEN C.; DAY, MITCH D.; POLATO, NICHOLAS R.; FITZPATRICK, SARAH W.; COONAN, TIMOTHY J.; CROOKS, KEVIN R.; DILLON, ADAM; GARCELON, DAVID K.; KING, JULIE L.; BOSER, CHRISTINA L.; GOULD, NICHOLAS; ANDELT, WILLIAM F.

    2016-01-01

    The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of 6 subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction-site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1–89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland gray foxes, and vice versa, indicating genetic drift drives genome-wide divergence. Nonetheless, outlier tests identified 3.6–6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness, and reduced adaptive potential. PMID:26992010

  6. Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis).

    Science.gov (United States)

    Funk, W Chris; Lovich, Robert E; Hohenlohe, Paul A; Hofman, Courtney A; Morrison, Scott A; Sillett, T Scott; Ghalambor, Cameron K; Maldonado, Jesus E; Rick, Torben C; Day, Mitch D; Polato, Nicholas R; Fitzpatrick, Sarah W; Coonan, Timothy J; Crooks, Kevin R; Dillon, Adam; Garcelon, David K; King, Julie L; Boser, Christina L; Gould, Nicholas; Andelt, William F

    2016-05-01

    The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction-site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1-89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome-wide divergence. Nonetheless, outlier tests identified 3.6-6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential. © 2016 John Wiley & Sons Ltd.

  7. An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism.

    Science.gov (United States)

    Mélade, Julien; Wieseke, Nicolas; Ramasindrazana, Beza; Flores, Olivier; Lagadec, Erwan; Gomard, Yann; Goodman, Steven M; Dellagi, Koussay; Pascalis, Hervé

    2016-04-12

    An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.

  8. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    International Nuclear Information System (INIS)

    Brenes, J.C.; Broiz, A.C.; Bassi, G.S.; Schwarting, R.K.W.; Brandão, M.L.

    2012-01-01

    Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by Y -aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG

  9. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    Energy Technology Data Exchange (ETDEWEB)

    Brenes, J.C. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Broiz, A.C.; Bassi, G.S. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Schwarting, R.K.W. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Brandão, M.L. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-09

    Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by {sub Y}-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

  10. Evolutionary Expectations

    DEFF Research Database (Denmark)

    Nash, Ulrik William

    2014-01-01

    , they are correlated among people who share environments because these individuals satisfice within their cognitive bounds by using cues in order of validity, as opposed to using cues arbitrarily. Any difference in expectations thereby arise from differences in cognitive ability, because two individuals with identical...... cognitive bounds will perceive business opportunities identically. In addition, because cues provide information about latent causal structures of the environment, changes in causality must be accompanied by changes in cognitive representations if adaptation is to be maintained. The concept of evolutionary......The concept of evolutionary expectations descends from cue learning psychology, synthesizing ideas on rational expectations with ideas on bounded rationality, to provide support for these ideas simultaneously. Evolutionary expectations are rational, but within cognitive bounds. Moreover...

  11. [Evolutionary medicine].

    Science.gov (United States)

    Wjst, M

    2013-12-01

    Evolutionary medicine allows new insights into long standing medical problems. Are we "really stoneagers on the fast lane"? This insight might have enormous consequences and will allow new answers that could never been provided by traditional anthropology. Only now this is made possible using data from molecular medicine and systems biology. Thereby evolutionary medicine takes a leap from a merely theoretical discipline to practical fields - reproductive, nutritional and preventive medicine, as well as microbiology, immunology and psychiatry. Evolutionary medicine is not another "just so story" but a serious candidate for the medical curriculum providing a universal understanding of health and disease based on our biological origin. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Evolutionary Awareness

    Directory of Open Access Journals (Sweden)

    Gregory Gorelik

    2014-10-01

    Full Text Available In this article, we advance the concept of “evolutionary awareness,” a metacognitive framework that examines human thought and emotion from a naturalistic, evolutionary perspective. We begin by discussing the evolution and current functioning of the moral foundations on which our framework rests. Next, we discuss the possible applications of such an evolutionarily-informed ethical framework to several domains of human behavior, namely: sexual maturation, mate attraction, intrasexual competition, culture, and the separation between various academic disciplines. Finally, we discuss ways in which an evolutionary awareness can inform our cross-generational activities—which we refer to as “intergenerational extended phenotypes”—by helping us to construct a better future for ourselves, for other sentient beings, and for our environment.

  13. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

    Science.gov (United States)

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-09-29

    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

  14. Contemporary issues in evolutionary biology

    Indian Academy of Sciences (India)

    These discussions included, among others, the possible consequences of nonDNA-based inheritance—epigenetics and cultural evolution, niche construction, and developmental mechanisms on our understanding of the evolutionary process, speciation, complexity in biology, and constructing a formal evolutionary theory.

  15. Evolutionary Statistical Procedures

    CERN Document Server

    Baragona, Roberto; Poli, Irene

    2011-01-01

    This proposed text appears to be a good introduction to evolutionary computation for use in applied statistics research. The authors draw from a vast base of knowledge about the current literature in both the design of evolutionary algorithms and statistical techniques. Modern statistical research is on the threshold of solving increasingly complex problems in high dimensions, and the generalization of its methodology to parameters whose estimators do not follow mathematically simple distributions is underway. Many of these challenges involve optimizing functions for which analytic solutions a

  16. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

    International Nuclear Information System (INIS)

    Merini, Luciano J.; Bobillo, Cecilia; Cuadrado, Virginia; Corach, Daniel; Giulietti, Ana M.

    2009-01-01

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg -1 of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P 450 or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P 450 . Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

  17. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Merini, Luciano J. [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Bobillo, Cecilia [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Cuadrado, Virginia [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Corach, Daniel [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Giulietti, Ana M., E-mail: agiule@ffyb.uba.a [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina)

    2009-11-15

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg{sup -1} of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P{sub 450} or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P{sub 450}. Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

  18. Clustering mechanism of oxocarboxylic acids involving hydration reaction: Implications for the atmospheric models

    Science.gov (United States)

    Liu, Ling; Kupiainen-Määttä, Oona; Zhang, Haijie; Li, Hao; Zhong, Jie; Kurtén, Theo; Vehkamäki, Hanna; Zhang, Shaowen; Zhang, Yunhong; Ge, Maofa; Zhang, Xiuhui; Li, Zesheng

    2018-06-01

    The formation of atmospheric aerosol particles from condensable gases is a dominant source of particulate matter in the boundary layer, but the mechanism is still ambiguous. During the clustering process, precursors with different reactivities can induce various chemical reactions in addition to the formation of hydrogen bonds. However, the clustering mechanism involving chemical reactions is rarely considered in most of the nucleation process models. Oxocarboxylic acids are common compositions of secondary organic aerosol, but the role of oxocarboxylic acids in secondary organic aerosol formation is still not fully understood. In this paper, glyoxylic acid, the simplest and the most abundant atmospheric oxocarboxylic acid, has been selected as a representative example of oxocarboxylic acids in order to study the clustering mechanism involving hydration reactions using density functional theory combined with the Atmospheric Clusters Dynamic Code. The hydration reaction of glyoxylic acid can occur either in the gas phase or during the clustering process. Under atmospheric conditions, the total conversion ratio of glyoxylic acid to its hydration reaction product (2,2-dihydroxyacetic acid) in both gas phase and clusters can be up to 85%, and the product can further participate in the clustering process. The differences in cluster structures and properties induced by the hydration reaction lead to significant differences in cluster formation rates and pathways at relatively low temperatures.

  19. Mechanisms involved in metformin action in the treatment of polycystic ovary syndrome.

    Science.gov (United States)

    Motta, A B

    2009-01-01

    The N, N' dimethyl-biguanide : Metformin is an antidiabetic drug that increases glucose utilization in insulin-sensitive tissues. As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS. Currently, metformin is used to induce ovulation and during early pregnancy in PCOS patients, however, a complete knowledge of the metformin action has not been achieved yet. This review describes beyond the classical reproductive action of metformin and explores other benefits of the drug. In addition, the present work discusses the molecular mechanisms involved further than the classical pathway that involves the AMP-activated protein kinase.

  20. Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.

    Science.gov (United States)

    Cervantes-Paz, Braulio; Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús

    Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds.

  1. Evolutionary robotics

    Indian Academy of Sciences (India)

    In evolutionary robotics, a suitable robot control system is developed automatically through evolution due to the interactions between the robot and its environment. It is a complicated task, as the robot and the environment constitute a highly dynamical system. Several methods have been tried by various investigators to ...

  2. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  3. Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

    Science.gov (United States)

    Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

    Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Peeling back the evolutionary layers of molecular mechanisms responsive to exercise-stress in the skeletal muscle of the racing horse.

    Science.gov (United States)

    Kim, Hyeongmin; Lee, Taeheon; Park, Woncheoul; Lee, Jin Woo; Kim, Jaemin; Lee, Bo-Young; Ahn, Hyeonju; Moon, Sunjin; Cho, Seoae; Do, Kyoung-Tag; Kim, Heui-Soo; Lee, Hak-Kyo; Lee, Chang-Kyu; Kong, Hong-Sik; Yang, Young-Mok; Park, Jongsun; Kim, Hak-Min; Kim, Byung Chul; Hwang, Seungwoo; Bhak, Jong; Burt, Dave; Park, Kyoung-Do; Cho, Byung-Wook; Kim, Heebal

    2013-06-01

    The modern horse (Equus caballus) is the product of over 50 million yrs of evolution. The athletic abilities of the horse have been enhanced during the past 6000 yrs under domestication. Therefore, the horse serves as a valuable model to understand the physiology and molecular mechanisms of adaptive responses to exercise. The structure and function of skeletal muscle show remarkable plasticity to the physical and metabolic challenges following exercise. Here, we reveal an evolutionary layer of responsiveness to exercise-stress in the skeletal muscle of the racing horse. We analysed differentially expressed genes and their co-expression networks in a large-scale RNA-sequence dataset comparing expression before and after exercise. By estimating genome-wide dN/dS ratios using six mammalian genomes, and FST and iHS using re-sequencing data derived from 20 horses, we were able to peel back the evolutionary layers of adaptations to exercise-stress in the horse. We found that the oldest and thickest layer (dN/dS) consists of system-wide tissue and organ adaptations. We further find that, during the period of horse domestication, the older layer (FST) is mainly responsible for adaptations to inflammation and energy metabolism, and the most recent layer (iHS) for neurological system process, cell adhesion, and proteolysis.

  5. Evolutionary Explanations of Eating Disorders

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    Igor Kardum

    2008-12-01

    Full Text Available This article reviews several most important evolutionary mechanisms that underlie eating disorders. The first part clarifies evolutionary foundations of mental disorders and various mechanisms leading to their development. In the second part selective pressures and evolved adaptations causing contemporary epidemic of obesity as well as differences in dietary regimes and life-style between modern humans and their ancestors are described. Concerning eating disorders, a number of current evolutionary explanations of anorexia nervosa are presented together with their main weaknesses. Evolutionary explanations of eating disorders based on the reproductive suppression hypothesis and its variants derived from kin selection theory and the model of parental manipulation were elaborated. The sexual competition hypothesis of eating disorder, adapted to flee famine hypothesis as well as explanation based on the concept of social attention holding power and the need to belonging were also explained. The importance of evolutionary theory in modern conceptualization and research of eating disorders is emphasized.

  6. Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

    Directory of Open Access Journals (Sweden)

    M. H. Mohd. Sani

    2012-01-01

    Full Text Available Muntingia calabura L. (family Elaeocarpaceae has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test and thermal (hot plate test models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05 antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO donor, NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS, methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP pathway, or their combination also caused significant (P<0.05 change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

  7. Mechanisms involved in the chemical inhibition of the Eosin-sensitized photooxidation of trypsin

    Energy Technology Data Exchange (ETDEWEB)

    Rizzuto, F.; Spikes, J.D.

    1975-01-01

    A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semireduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co/sup + +/, Cu/sup + +/ and Mn/sup + +/ reacted only slowly with triplet and with semioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.

  8. Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

    Science.gov (United States)

    Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

    2014-10-01

    Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats.

    Science.gov (United States)

    Lozano-Cuenca, J; González-Hernández, A; López-Canales, O A; Villagrana-Zesati, J R; Rodríguez-Choreão, J D; Morín-Zaragoza, R; Castillo-Henkel, E F; López-Canales, J S

    2017-08-07

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (Pclobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  10. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

  11. An evolutionary medicine approach to understanding factors that contribute to chronic obstructive pulmonary disease.

    Science.gov (United States)

    Aoshiba, Kazutetsu; Tsuji, Takao; Itoh, Masayuki; Yamaguchi, Kazuhiro; Nakamura, Hiroyuki

    2015-01-01

    Although many studies have been published on the causes and mechanisms of chronic obstructive pulmonary disease (COPD), the reason for the existence of COPD and the reasons why COPD develops in humans have hardly been studied. Evolutionary medical approaches are required to explain not only the proximate factors, such as the causes and mechanisms of a disease, but the ultimate (evolutionary) factors as well, such as why the disease is present and why the disease develops in humans. According to the concepts of evolutionary medicine, disease susceptibility is acquired as a result of natural selection during the evolutionary process of traits linked to the genes involved in disease susceptibility. In this paper, we discuss the following six reasons why COPD develops in humans based on current evolutionary medical theories: (1) evolutionary constraints; (2) mismatch between environmental changes and evolution; (3) co-evolution with pathogenic microorganisms; (4) life history trade-off; (5) defenses and their costs, and (6) reproductive success at the expense of health. Our perspective pursues evolutionary answers to the fundamental question, 'Why are humans susceptible to this common disease, COPD, despite their long evolutionary history?' We believe that the perspectives offered by evolutionary medicine are essential for researchers to better understand the significance of their work.

  12. The Motivational Foundations of Prosocial Behavior From A Developmental Perspective-Evolutionary Roots and Key Psychological Mechanisms: Introduction to the Special Section.

    Science.gov (United States)

    Davidov, Maayan; Vaish, Amrisha; Knafo-Noam, Ariel; Hastings, Paul D

    2016-11-01

    Prosocial behavior is versatile, multifaceted, and complex. This special section seeks to advance coherent, integrative understanding of prosocial development by addressing this topic through the prism of motivations. This conceptual Introduction presents key ideas that provide a framework for thinking about motivation for prosocial behavior and its development. It outlines the evolutionary roots of prosocial behavior, underscoring the interdependent roles of nature and nurture. This is followed by a discussion of several key psychological mechanisms reflecting different motivations for prosocial action (empathy for a distressed other, concern about another's goal, desire to act in accordance with internalized prosocial norms, and guilt). We discuss the critical components of each motivation and highlight pertinent contributions of the special section articles. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

  13. Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

    Directory of Open Access Journals (Sweden)

    Tamas Kiss

    Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

  14. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-02-01

    The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

  15. Proteomics in evolutionary ecology.

    Science.gov (United States)

    Baer, B; Millar, A H

    2016-03-01

    Evolutionary ecologists are traditionally gene-focused, as genes propagate phenotypic traits across generations and mutations and recombination in the DNA generate genetic diversity required for evolutionary processes. As a consequence, the inheritance of changed DNA provides a molecular explanation for the functional changes associated with natural selection. A direct focus on proteins on the other hand, the actual molecular agents responsible for the expression of a phenotypic trait, receives far less interest from ecologists and evolutionary biologists. This is partially due to the central dogma of molecular biology that appears to define proteins as the 'dead-end of molecular information flow' as well as technical limitations in identifying and studying proteins and their diversity in the field and in many of the more exotic genera often favored in ecological studies. Here we provide an overview of a newly forming field of research that we refer to as 'Evolutionary Proteomics'. We point out that the origins of cellular function are related to the properties of polypeptide and RNA and their interactions with the environment, rather than DNA descent, and that the critical role of horizontal gene transfer in evolution is more about coopting new proteins to impact cellular processes than it is about modifying gene function. Furthermore, post-transcriptional and post-translational processes generate a remarkable diversity of mature proteins from a single gene, and the properties of these mature proteins can also influence inheritance through genetic and perhaps epigenetic mechanisms. The influence of post-transcriptional diversification on evolutionary processes could provide a novel mechanistic underpinning for elements of rapid, directed evolutionary changes and adaptations as observed for a variety of evolutionary processes. Modern state-of the art technologies based on mass spectrometry are now available to identify and quantify peptides, proteins, protein

  16. Physical mechanism or evolutionary trade-off? Factors dictating the relationship between metabolic rate and ambient temperature in carabid beetles.

    Science.gov (United States)

    Gudowska, Agnieszka; Schramm, Bartosz W; Czarnoleski, Marcin; Kozłowski, Jan; Bauchinger, Ulf

    2017-08-01

    The tight association between ambient temperature (T) and metabolic rate (MR) is a common occurrence in ectotherms, but the determinants of this association are not fully understood. This study examined whether the relationship between MR and T is the same among individuals, as predicted by the Universal Temperature Dependence hypothesis, or whether this relationship differs between them. We used flow-through respirometry to measure standard MR and to determine gas exchange patterns for 111 individuals of three Carabidae species which differ in size (Abax ovalis, Carabus linnei and C. coriaceus), exposed to four different temperatures (ten individuals of each species measured at 6, 11, 16 and 21°C). We found a significant interaction between ln body mass and the inverse of temperature, indicating that in a given species, the effect of temperature on MR was weaker in larger individuals than in smaller individuals. Overall, this finding shows that the thermal dependence of MR is not body mass invariant. We observed three types of gas exchange patterns among beetles: discontinuous, cyclic and continuous. Additionally, the appearance of these patterns was associated with MR and T. Evolution in diverse terrestrial environments could affect diverse ventilation patterns, which accommodate changes in metabolism in response to temperature variation. In conclusion, explaining the variance in metabolism only through fundamental physical laws of thermodynamics, as predicted by the Universal Temperature Dependence hypothesis, appears to oversimplify the complexity of nature, ignoring evolutionary trade-offs that should be taken into account in the temperature - metabolism relationship. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Evolutionary institutionalism.

    Science.gov (United States)

    Fürstenberg, Dr Kai

    Institutions are hard to define and hard to study. Long prominent in political science have been two theories: Rational Choice Institutionalism (RCI) and Historical Institutionalism (HI). Arising from the life sciences is now a third: Evolutionary Institutionalism (EI). Comparative strengths and weaknesses of these three theories warrant review, and the value-to-be-added by expanding the third beyond Darwinian evolutionary theory deserves consideration. Should evolutionary institutionalism expand to accommodate new understanding in ecology, such as might apply to the emergence of stability, and in genetics, such as might apply to political behavior? Core arguments are reviewed for each theory with more detailed exposition of the third, EI. Particular attention is paid to EI's gene-institution analogy; to variation, selection, and retention of institutional traits; to endogeneity and exogeneity; to agency and structure; and to ecosystem effects, institutional stability, and empirical limitations in behavioral genetics. RCI, HI, and EI are distinct but complementary. Institutional change, while amenable to rational-choice analysis and, retrospectively, to criticaljuncture and path-dependency analysis, is also, and importantly, ecological. Stability, like change, is an emergent property of institutions, which tend to stabilize after change in a manner analogous to allopatric speciation. EI is more than metaphorically biological in that institutional behaviors are driven by human behaviors whose evolution long preceded the appearance of institutions themselves.

  18. Structure/Function Studies of the α4 Subunit Reveal Evolutionary Loss of a GlyR Subtype Involved in Startle and Escape Responses

    Directory of Open Access Journals (Sweden)

    Sophie Leacock

    2018-01-01

    Full Text Available Inhibitory glycine receptors (GlyRs are pentameric ligand-gated anion channels with major roles in startle disease/hyperekplexia (GlyR α1, cortical neuronal migration/autism spectrum disorder (GlyR α2, and inflammatory pain sensitization/rhythmic breathing (GlyR α3. However, the role of the GlyR α4 subunit has remained enigmatic, because the corresponding human gene (GLRA4 is thought to be a pseudogene due to an in-frame stop codon at position 390 within the fourth membrane-spanning domain (M4. Despite this, a recent genetic study has implicated GLRA4 in intellectual disability, behavioral problems and craniofacial anomalies. Analyzing data from sequenced genomes, we found that GlyR α4 subunit genes are predicted to be intact and functional in the majority of vertebrate species—with the exception of humans. Cloning of human GlyR α4 cDNAs excluded alternative splicing and RNA editing as mechanisms for restoring a full-length GlyR α4 subunit. Moreover, artificial restoration of the missing conserved arginine (R390 in the human cDNA was not sufficient to restore GlyR α4 function. Further bioinformatic and mutagenesis analysis revealed an additional damaging substitution at K59 that ablates human GlyR α4 function, which is not present in other vertebrate GlyR α4 sequences. The substitutions K59 and X390 were also present in the genome of an ancient Denisovan individual, indicating that GLRA4 has been a pseudogene for at least 30,000–50,000 years. In artificial synapses, we found that both mouse and gorilla α4β GlyRs mediate synaptic currents with unusually slow decay kinetics. Lastly, to gain insights into the biological role of GlyR α4 function, we studied the duplicated genes glra4a and glra4b in zebrafish. While glra4b expression is restricted to the retina, using a novel tol2-GAL4FF gene trap line (SAIGFF16B, we found that the zebrafish GlyR α4a subunit gene (glra4a is strongly expressed in spinal cord and hindbrain commissural

  19. Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms.

    Science.gov (United States)

    Vidal-Dupiol, Jeremie; Adjeroud, Mehdi; Roger, Emmanuel; Foure, Laurent; Duval, David; Mone, Yves; Ferrier-Pages, Christine; Tambutte, Eric; Tambutte, Sylvie; Zoccola, Didier; Allemand, Denis; Mitta, Guillaume

    2009-08-04

    Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28 degrees C to 32 degrees C over 15 days. A second control set kept at constant temperature (28 degrees C). The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching) and the non stressed states (control) were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function) were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin) contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich). Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress. Under thermal stress

  20. Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms

    Directory of Open Access Journals (Sweden)

    Tambutte Sylvie

    2009-08-01

    Full Text Available Abstract Background Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. Results In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28°C to 32°C over 15 days. A second control set kept at constant temperature (28°C. The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching and the non stressed states (control were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich. Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress

  1. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

    Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

    2010-05-26

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  2. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    International Nuclear Information System (INIS)

    Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

    2010-01-01

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells

  3. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Paola Massi

    2010-05-01

    Full Text Available Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  4. A molecular mechanism for the origin of a key evolutionary innovation, the bird beak and palate, revealed by an integrative approach to major transitions in vertebrate history.

    Science.gov (United States)

    Bhullar, Bhart-Anjan S; Morris, Zachary S; Sefton, Elizabeth M; Tok, Atalay; Tokita, Masayoshi; Namkoong, Bumjin; Camacho, Jasmin; Burnham, David A; Abzhanov, Arhat

    2015-07-01

    The avian beak is a key evolutionary innovation whose flexibility has permitted birds to diversify into a range of disparate ecological niches. We approached the problem of the mechanism behind this innovation using an approach bridging paleontology, comparative anatomy, and experimental developmental biology. First, we used fossil and extant data to show the beak is distinctive in consisting of fused premaxillae that are geometrically distinct from those of ancestral archosaurs. To elucidate underlying developmental mechanisms, we examined candidate gene expression domains in the embryonic face: the earlier frontonasal ectodermal zone (FEZ) and the later midfacial WNT-responsive region, in birds and several reptiles. This permitted the identification of an autapomorphic median gene expression region in Aves. To test the mechanism, we used inhibitors of both pathways to replicate in chicken the ancestral amniote expression. Altering the FEZ altered later WNT responsiveness to the ancestral pattern. Skeletal phenotypes from both types of experiments had premaxillae that clustered geometrically with ancestral fossil forms instead of beaked birds. The palatal region was also altered to a more ancestral phenotype. This is consistent with the fossil record and with the tight functional association of avian premaxillae and palate in forming a kinetic beak. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  5. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    Directory of Open Access Journals (Sweden)

    J. Lozano-Cuenca

    Full Text Available Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10–9–10–5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10–7.5–10–5 M. The present outcome was not modified by 10–6 M atropine (an antagonist of muscarinic acetylcholine receptors, 3.1×10–7 M glibenclamide (an ATP-sensitive K+ channel blocker, 10–3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker, 10–5 M indomethacin (a prostaglandin synthesis inhibitor, 10–5 M clotrimazole (a cytochrome P450 inhibitor or 10–5 M cycloheximide (a general protein synthesis inhibitor. Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05 by 10–5 M L-NAME (a direct inhibitor of nitric oxide synthase, 10–7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase, 10–6 M KT 5823 (an inhibitor of protein kinase G, 10–2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker and 10–7 M apamin plus 10–7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively, and was blocked by 8×10–2 M potassium (a high concentration and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  6. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

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    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  7. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

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    Andrew P. Wojtovich

    2013-03-01

    Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

  8. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

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    Carlo Travaglini-Allocatelli

    2013-01-01

    Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

  9. Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

    Science.gov (United States)

    Nishimura, M; Obana, N; Yagasaki, O; Yanagiya, I

    1984-05-01

    Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

  10. Mechanism of oxidative stress involved in the toxicity of ZnO nanoparticles against eukaryotic cells

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    M. Saliani

    2016-01-01

    Full Text Available ZnO NPs (zinc oxide nanoparticles has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

  11. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth.

    Science.gov (United States)

    Commandeur, Arno E; Styer, Aaron K; Teixeira, Jose M

    2015-01-01

    Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and in vivo, human syndrome

  12. A novel puf-A gene predicted from evolutionary analysis is involved in the development of eyes and primordial germ-cells.

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    Ming-Wei Kuo

    Full Text Available Although the human genome project has been completed for some time, the issue of the number of transcribed genes with identifiable biological functions remains unresolved. We used zebrafish as a model organism to study the functions of Ka/Ks-predicted novel human exons, which were identified from a comparative evolutionary genomics analysis.In this study, a novel gene, designated as puf-A, was cloned and functionally characterized, and its homologs in zebrafish, mouse, and human were identified as one of the three homolog clusters which were consisted of 14 related proteins with Puf repeats. Computer modeling of human Puf-A structure and a pull-down assay for interactions with RNA targets predicted that it was a RNA-binding protein. Specifically, Puf-A contained a special six Puf-repeat domain, which constituted a unique superhelix half doughnut-shaped Puf domain with a topology similar to, but different from the conventional eight-repeat Pumilio domain. Puf-A transcripts were uniformly distributed in early embryos, but became restricted primarily to eyes and ovaries at a later stage of development. In mice, puf-A expression was detected primarily in retinal ganglion and pigmented cells. Knockdown of puf-A in zebrafish embryos resulted in microphthalmia, a small head, and abnormal primordial germ-cell (PGC migration. The latter was confirmed by microinjecting into embryos puf-A siRNA containing nanos 3' UTR that expressed in PGC only. The importance of Puf-A in the maturation of germline stem cells was also implicated by its unique expression in the most primitive follicles (stage I in adult ovaries, followed by a sharp decline of expression in later stages of folliculogenesis. Taken together, our study shows that puf-A plays an important role not only in eye development, but also in PGC migration and the specification of germ cell lineage. These studies represent an exemplary implementation of a unique platform to uncover unknown function(s of

  13. QTL analysis of frost damage in pea suggests different mechanisms involved in frost tolerance.

    Science.gov (United States)

    Klein, Anthony; Houtin, Hervé; Rond, Céline; Marget, Pascal; Jacquin, Françoise; Boucherot, Karen; Huart, Myriam; Rivière, Nathalie; Boutet, Gilles; Lejeune-Hénaut, Isabelle; Burstin, Judith

    2014-06-01

    Avoidance mechanisms and intrinsic resistance are complementary strategies to improve winter frost tolerance and yield potential in field pea. The development of the winter pea crop represents a major challenge to expand plant protein production in temperate areas. Breeding winter cultivars requires the combination of freezing tolerance as well as high seed productivity and quality. In this context, we investigated the genetic determinism of winter frost tolerance and assessed its genetic relationship with yield and developmental traits. Using a newly identified source of frost resistance, we developed a population of recombinant inbred lines and evaluated it in six environments in Dijon and Clermont-Ferrand between 2005 and 2010. We developed a genetic map comprising 679 markers distributed over seven linkage groups and covering 947.1 cM. One hundred sixty-one quantitative trait loci (QTL) explaining 9-71 % of the phenotypic variation were detected across the six environments for all traits measured. Two clusters of QTL mapped on the linkage groups III and one cluster on LGVI reveal the genetic links between phenology, morphology, yield-related traits and frost tolerance in winter pea. QTL clusters on LGIII highlighted major developmental gene loci (Hr and Le) and the QTL cluster on LGVI explained up to 71 % of the winter frost damage variation. This suggests that a specific architecture and flowering ideotype defines frost tolerance in winter pea. However, two consistent frost tolerance QTL on LGV were independent of phenology and morphology traits, showing that different protective mechanisms are involved in frost tolerance. Finally, these results suggest that frost tolerance can be bred independently to seed productivity and quality.

  14. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    International Nuclear Information System (INIS)

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-01-01

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation

  15. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

    Science.gov (United States)

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

    2016-12-06

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

  16. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan (China); Cao, Hui [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hongjie [Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL (United States); Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiang, Ming, E-mail: xiangming@mails.tjmu.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  17. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    Science.gov (United States)

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Helminths and Cancers From the Evolutionary Perspective.

    Science.gov (United States)

    Scholte, Larissa L S; Pascoal-Xavier, Marcelo A; Nahum, Laila A

    2018-01-01

    Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes ( Schistosoma haematobium, Schistosoma japonicum , and Schistosoma mansoni ) and liver flukes ( Clonorchis sinensis and Opisthorchis viverrini ) are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine) and may contribute to parasite and cancer research.

  19. Helminths and Cancers From the Evolutionary Perspective

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    Larissa L. S. Scholte

    2018-04-01

    Full Text Available Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes (Schistosoma haematobium, Schistosoma japonicum, and Schistosoma mansoni and liver flukes (Clonorchis sinensis and Opisthorchis viverrini are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine and may contribute to parasite and cancer research.

  20. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

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    Bassam R Ali

    Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

  1. Mechanisms and secondary factors involved in the induction of radiation transformation in vitro

    International Nuclear Information System (INIS)

    Little, J.B.

    1983-01-01

    The long term of this research program was to gain information concerning the mechanisms that determine the carcinogenic effects of ionizing radiation, particularly high LET radiation exposure. The experimental approach involves parallel studies of the induction of malignant transformation in BALB/3T3 cells and of specific gene mutations in human lymphoblastoid cells. Emphasis was on the biologic effects of internally incorporated Auger electron emitting radionuclides and the initiation of studies to determine the effects of low dose-rate neutron exposure. Auger electron irradiation sever as a model for high LET-type radiation effects and as an experimental tool for studying the effects of radiation at specific sites within the cell. Auger-emitting radiosotopes are commonly used in clinical nuclear medicine, rendering them a potential hazard to human populations. We examined the influence of cellular localization of Auger-emitting radionuclides and the spectrum of energy distribution in DNA on their mutagenic, cytogenetic, and transformational effects. The effects of 125 I (an energetic beta emitter) were compared. We studied the induction of cytogenetic changes by 125 I exposure of the cell membrane, as well as its potential to promote (enhance) transformation initiated by low dose external x-ray exposure. We will investigate the Relative Biological Effectiveness for mutagenesis and transformation of low doses of fast neutrons delivered continuously at variable low dose-rates. 34 refs., 1 tab

  2. Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

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    Williams Mandy

    2005-01-01

    Full Text Available Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16 INK4a and p14 ARF . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 INK4a /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

  3. Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium breve soluble factors.

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    Elise Heuvelin

    Full Text Available OBJECTIVES: Soluble factors released by Bifidobacterium breve C50 (Bb alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM and other Gram(+ commensal bacteria to dampen inflammatory chemokine secretion. METHODS: TNFalpha-induced chemokine (CXCL8 secretion and alteration of NF-kappaB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. RESULTS: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kappaB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkappaB-alpha molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. CONCLUSIONS: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylations involved in inflammatory processes and by protective conditioning of dendritic cells.

  4. Interfacial Mechanics Analysis of a Brittle Coating–Ductile Substrate System Involved in Thermoelastic Contact

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    Chi Zhang

    2017-02-01

    Full Text Available In this paper, interfacial stress analysis for a brittle coating/ductile substrate system, which is involved in a sliding contact with a rigid ball, is presented. By combining interface mechanics theory and the image point method, stress and displacement responses within a coated material for normal load, tangential load, and thermal load are obtained; further, the Green’s functions are established. The effects of coating thickness, friction coefficient, and a coating’s thermoelastic properties on the interfacial shear stress, τxz, and transverse stress, σxx, distributions are discussed in detail. A phenomenon, where interfacial shear stress tends to be relieved by frictional heating, is found in the case of a coating material’s thermal expansion coefficient being less than a substrate material’s thermal expansion coefficient. Additionally, numerical results show that distribution of interfacial stress can be altered and, therefore, interfacial damage can be modified by adjusting a coating’s structural parameters and thermoelastic properties.

  5. Involvement of Sodium Nitroprusside (SNP in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars

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    Aung H. Naing

    2017-11-01

    Full Text Available Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.

  6. Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

    Science.gov (United States)

    Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

    2017-01-01

    Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

  7. Freud: the first evolutionary psychologist?

    Science.gov (United States)

    LeCroy, D

    2000-04-01

    An evolutionary perspective on attachment theory and psychoanalytic theory brings these two fields together in interesting ways. Application of the evolutionary principle of parent-offspring conflict to attachment theory suggests that attachment styles represent context-sensitive, evolved (adaptive) behaviors. In addition, an emphasis on offspring counter-strategies to adult reproductive strategies leads to consideration of attachment styles as overt manifestations of psychodynamic mediating processes, including the defense mechanisms of repression and reaction formation.

  8. Toward a general evolutionary theory of oncogenesis.

    Science.gov (United States)

    Ewald, Paul W; Swain Ewald, Holly A

    2013-01-01

    We propose an evolutionary framework, the barrier theory of cancer, which is based on the distinction between barriers to oncogenesis and restraints. Barriers are defined as mechanisms that prevent oncogenesis. Restraints, which are more numerous, inhibit but do not prevent oncogenesis. Processes that compromise barriers are essential causes of cancer; those that interfere with restraints are exacerbating causes. The barrier theory is built upon the three evolutionary processes involved in oncogenesis: natural selection acting on multicellular organisms to mold barriers and restraints, natural selection acting on infectious organisms to abrogate these protective mechanisms, and oncogenic selection which is responsible for the evolution of normal cells into cancerous cells. The barrier theory is presented as a first step toward the development of a general evolutionary theory of cancer. Its attributes and implications for intervention are compared with those of other major conceptual frameworks for understanding cancer: the clonal diversification model, the stem cell theory and the hallmarks of cancer. The barrier theory emphasizes the practical value of distinguishing between essential and exacerbating causes. It also stresses the importance of determining the scope of infectious causation of cancer, because individual pathogens can be responsible for multiple essential causes in infected cells.

  9. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms : Involvement of JNK and ERK MAP kinases

    NARCIS (Netherlands)

    Conde de la Rosa, L; Schoemaker, MH; Vrenken, TE; Buist-Homan, M; Havinga, R; Jansen, PLM; Moshage, H

    Background/Aims: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

  10. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: involvement of JNK and ERK MAP kinases

    NARCIS (Netherlands)

    Conde de la Rosa, Laura; Schoemaker, Marieke H.; Vrenken, Titia E.; Buist-Homan, Manon; Havinga, Rick; Jansen, Peter L. M.; Moshage, Han

    2006-01-01

    BACKGROUND/AIMS: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

  11. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

    International Nuclear Information System (INIS)

    Bull, R.J.; Miller, J.H.; Sasser, L.B.; Schultz, I.R.; Thrall, B.D.

    1998-01-01

    'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold

  12. The odyssey of a young gene: structure-function studies in human glutamate dehydrogenases reveal evolutionary-acquired complex allosteric regulation mechanisms.

    Science.gov (United States)

    Zaganas, Ioannis V; Kanavouras, Konstantinos; Borompokas, Nikolas; Arianoglou, Giovanna; Dimovasili, Christina; Latsoudis, Helen; Vlassi, Metaxia; Mastorodemos, Vasileios

    2014-01-01

    Mammalian glutamate dehydrogenase (GDH) catalyzes the reversible inter-conversion of glutamate to α-ketoglutarate and ammonia, interconnecting carbon skeleton and nitrogen metabolism. In addition, it functions as an energy switch by its ability to fuel the Krebs cycle depending on the energy status of the cell. As GDH lies at the intersection of several metabolic pathways, its activity is tightly regulated by several allosteric compounds that are metabolic intermediates. In contrast to other mammals that have a single GDH-encoding gene, humans and great apes possess two isoforms of GDH (hGDH1 and hGDH2, encoded by the GLUD1 and GLUD2 genes, respectively) with distinct regulation pattern, but remarkable sequence similarity (they differ, in their mature form, in only 15 of their 505 amino-acids). The GLUD2 gene is considered a very young gene, emerging from the GLUD1 gene through retro-position only recently (<23 million years ago). The new hGDH2 iso-enzyme, through random mutations and natural selection, is thought to have conferred an evolutionary advantage that helped its persistence through primate evolution. The properties of the two highly homologous human GDHs have been studied using purified recombinant hGDH1 and hGDH2 proteins obtained by expression of the corresponding cDNAs in Sf21 cells. According to these studies, in contrast to hGDH1 that maintains basal activity at 35-40 % of its maximal, hGDH2 displays low basal activity that is highly responsive to activation by rising levels of ADP and/or L-leucine which can also act synergistically. While hGDH1 is inhibited potently by GTP, hGDH2 shows remarkable GTP resistance. Furthermore, the two iso-enzymes are differentially inhibited by estrogens, polyamines and neuroleptics, and also differ in heat-lability. To elucidate the molecular mechanisms that underlie these different regulation patterns of the two iso-enzymes (and consequently the evolutionary adaptation of hGDH2 to a new functional role), we have

  13. Study of the Genes and Mechanism Involved in the Radioadaptive Response

    Science.gov (United States)

    Dasgupta, Pushan R.

    2009-01-01

    The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

  14. Evolutionary constrained optimization

    CERN Document Server

    Deb, Kalyanmoy

    2015-01-01

    This book makes available a self-contained collection of modern research addressing the general constrained optimization problems using evolutionary algorithms. Broadly the topics covered include constraint handling for single and multi-objective optimizations; penalty function based methodology; multi-objective based methodology; new constraint handling mechanism; hybrid methodology; scaling issues in constrained optimization; design of scalable test problems; parameter adaptation in constrained optimization; handling of integer, discrete and mix variables in addition to continuous variables; application of constraint handling techniques to real-world problems; and constrained optimization in dynamic environment. There is also a separate chapter on hybrid optimization, which is gaining lots of popularity nowadays due to its capability of bridging the gap between evolutionary and classical optimization. The material in the book is useful to researchers, novice, and experts alike. The book will also be useful...

  15. Evolutionary trade-offs between drought resistance mechanisms across a precipitation gradient in a seasonally dry tropical oak (Quercus oleoides).

    Science.gov (United States)

    Ramírez-Valiente, Jose A; Cavender-Bares, Jeannine

    2017-07-01

    In seasonally dry tropical forest regions, drought avoidance during the dry season coupled with high assimilation rates in the wet season is hypothesized to be an advantageous strategy for forest trees in regions with severe and long dry seasons. In contrast, where dry seasons are milder, drought tolerance coupled with a conservative resource-use strategy is expected to maximize carbon assimilation throughout the year. Tests of this hypothesis, particularly at the intraspecific level, have been seldom conducted. In this study, we tested the extent to which drought resistance mechanisms and rates of carbon assimilation have evolved under climates with varying dry season length and severity within Quercus oleoidesCham. and Schlect., a tropical dry forest species that is widely distributed in Central America. For this purpose, we conducted a greenhouse experiment where seedlings originating from five populations that vary in rainfall patterns were grown under different watering treatments. Our results revealed that populations from xeric climates with more severe dry seasons exhibited large mesophyllous leaves (with high specific leaf area, SLA), and leaf abscission in response to drought, consistent with a drought-avoidance strategy. In contrast, populations from more mesic climates with less severe dry seasons had small and thick sclerophyllous leaves with low SLA and reduced water potential at the turgor loss point (πtlp), consistent with a drought-tolerance strategy. Mesic populations also showed high plasticity in πtlp in response to water availability, indicating that osmotic adjustment to drought is an important component of this strategy. However, populations with mesophyllous leaves did not have higher maximum carbon assimilation rates under well-watered conditions. Furthermore, SLA was negatively associated with mass-based photosynthetic rates, contrary to expectations of the leaf economics spectrum, indicating that drought-resistance strategies are not

  16. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    Directory of Open Access Journals (Sweden)

    Sagai Masaru

    2011-12-01

    moderate oxidative stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1α are warranted.

  17. Microarray Analysis of the Molecular Mechanism Involved in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Cheng Tan

    2018-01-01

    Full Text Available Purpose. This study aimed to investigate the underlying molecular mechanisms of Parkinson’s disease (PD by bioinformatics. Methods. Using the microarray dataset GSE72267 from the Gene Expression Omnibus database, which included 40 blood samples from PD patients and 19 matched controls, differentially expressed genes (DEGs were identified after data preprocessing, followed by Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analyses. Protein-protein interaction (PPI network, microRNA- (miRNA- target regulatory network, and transcription factor- (TF- target regulatory networks were constructed. Results. Of 819 DEGs obtained, 359 were upregulated and 460 were downregulated. Two GO terms, “rRNA processing” and “cytoplasm,” and two KEGG pathways, “metabolic pathways” and “TNF signaling pathway,” played roles in PD development. Intercellular adhesion molecule 1 (ICAM1 was the hub node in the PPI network; hsa-miR-7-5p, hsa-miR-433-3p, and hsa-miR-133b participated in PD pathogenesis. Six TFs, including zinc finger and BTB domain-containing 7A, ovo-like transcriptional repressor 1, GATA-binding protein 3, transcription factor dp-1, SMAD family member 1, and quiescin sulfhydryl oxidase 1, were related to PD. Conclusions. “rRNA processing,” “cytoplasm,” “metabolic pathways,” and “TNF signaling pathway” were key pathways involved in PD. ICAM1, hsa-miR-7-5p, hsa-miR-433-3p, hsa-miR-133b, and the abovementioned six TFs might play important roles in PD development.

  18. Study of the mechanisms involved in the laser superficial hardening process of metallic alloys

    International Nuclear Information System (INIS)

    Silva, Edmara Marques Rodrigues da

    2001-01-01

    The laser superficial hardening process of a ferrous alloy (gray cast iron) and of an aluminum-silicon alloy was investigated in this work. These metallic alloys are used in the automobile industry for manufacturing cylinders and pistons, respectively. By application of individual pulses and single tracks, the involved mechanisms during the processing were studied. Variables such as energy density, power density, temporal width, beam diameter on the sample surface, atmosphere of the processing region, overlapping and scanning velocity. The hardened surface was characterized by optical and scanning electronic microscopy, dispersive energy microanalysis, X-ray mapping, X-ray diffraction, and measurements of roughness and Vickers microhardness. Depending on the processing parameters, it is possible to obtain different microstructures. The affected area of gray cast iron, can be hardened by remelting or transformation hardening (total or partial) if the reached temperature is higher or not that of melting temperature. Laser treatment originated new structures such as retained austenite, martensite and, occasionally, eutectic of cellular dendritic structure. Aluminum-silicon alloy does not have phase transformation in solid state, it can be hardened only by remelting. The increase of hardness is a function of the precipitation hardening process, which makes the silicon particles smaller and more disperse in the matrix. Maximal values of microhardness (700-1000 HV) were reached with the laser treatment in gray cast iron samples. The initial microhardness is of 242 HV. For aluminum-silicon alloy, the laser remelting increases the initial microhardness of 128 HV to the range of 160-320 HV. The found results give a new perspective for using the CLA/IPEN's laser in the heat treatment area. Besides providing a higher absorptivity to the materials, compared with the CO 2 laser, and optical fiber access, the superficial hardening with Nd:YAG laser, depending on the level of

  19. Evolutionary disarmament in interspecific competition.

    Science.gov (United States)

    Kisdi, E; Geritz, S A

    2001-12-22

    Competitive asymmetry, which is the advantage of having a larger body or stronger weaponry than a contestant, drives spectacular evolutionary arms races in intraspecific competition. Similar asymmetries are well documented in interspecific competition, yet they seldom lead to exaggerated traits. Here we demonstrate that two species with substantially different size may undergo parallel coevolution towards a smaller size under the same ecological conditions where a single species would exhibit an evolutionary arms race. We show that disarmament occurs for a wide range of parameters in an ecologically explicit model of competition for a single shared resource; disarmament also occurs in a simple Lotka-Volterra competition model. A key property of both models is the interplay between evolutionary dynamics and population density. The mechanism does not rely on very specific features of the model. Thus, evolutionary disarmament may be widespread and may help to explain the lack of interspecific arms races.

  20. Mechanisms involved in the psychological distress of Black Caribbeans in the United States

    Science.gov (United States)

    Govia, Ishtar O.

    The mental health of ethnic minorities in the United States is of urgent concern. The accelerated growth of groups of ethnic minorities and immigrants in the United States and the stressors to which they are exposed, implores academic researchers to investigate more deeply health disparities and the factors that exacerbate or minimize such inequalities. This dissertation attended to that concern. It used data from the National Survey of American Life (NSAL), the first survey with a national representative sample of Black Caribbeans, to explore mechanisms that involved in the psychological distress of Black Caribbeans in the United States. In a series of three studies, the dissertation investigated the role and consequence of (1) chronic discrimination, immigration factors, and closeness to ethnic and racial groups; (2) personal control and social support; and (3) family relations and social roles in the psychological distress of Black Caribbeans. Study 1 examined how the associations between discrimination and psychological distress were buffered or exacerbated by closeness to ethnic group and closeness to racial group. It also examined how these associations differed depending on immigration factors. Results indicated that the buffering or exacerbating effect of ethnic and racial group closeness varied according to the type of discrimination (subtle or severe) and were more pronounced among those born in the United States. Using the stress process framework, Study 2 tested moderation and mediation models of the effects of social support and personal control in the association between discrimination and distress. Results from a series of analyses on 579 respondents suggested that personal control served as a mediator in this relationship and that emotional support exerted a direct distress deterring function. Study 3 investigated sex differences in the associations between social roles, intergenerational family relationship perceptions and distress. Results

  1. A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α

    Directory of Open Access Journals (Sweden)

    Dickinson Bryony A

    2009-06-01

    Full Text Available Abstract Background Long-term depression (LTD in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs and muscarinic acethycholine receptors (mAChRs. Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC, it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-α. Results Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-α. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms. Conclusion Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-α. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-α.

  2. A Computationally-Efficient, Multi-Mechanism Based Framework for the Comprehensive Modeling of the Evolutionary Behavior of Shape Memory Alloys

    Science.gov (United States)

    Saleeb, Atef F.; Vaidyanathan, Raj

    2016-01-01

    The report summarizes the accomplishments made during the 4-year duration of the project. Here, the major emphasis is placed on the different tasks performed by the two research teams; i.e., the modeling activities by the University of Akron (UA) team and the experimental and neutron diffraction studies conducted by the University of Central Florida (UCF) team, during this 4-year period. Further technical details are given in the upcoming sections by UA and UCF for each of the milestones/years (together with the corresponding figures and captions).The project majorly involved the development, validation, and application of a general theoretical model that is capable of capturing the nonlinear hysteretic responses, including pseudoelasticity, shape memory effect, rate-dependency, multi-axiality, asymmetry in tension versus compression response of shape memory alloys. Among the targeted goals for the SMA model was its ability to account for the evolutionary character response (including transient and long term behavior under sustained cycles) for both conventional and high temperature (HT) SMAs, as well as being able to simulate some of the devices which exploit these unique material systems. This required extensive (uniaxial and multi-axial) experiments needed to guide us in calibrating and characterizing the model. Moreover, since the model is formulated on the theoretical notion of internal state variables (ISVs), neutron diffraction experiments were needed to establish the linkage between the micromechanical changes and these ISVs. In addition, the design of the model should allow easy implementation in large scale finite element application to study the behavior of devices making use of these SMA materials under different loading controls. Summary of the activities, progress/achievements made during this period is given below in details for the University of Akron and the University (Section 2.0) of Central Florida (Section 3.0).

  3. Mechanisms involved in the evasion of the host defence by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Kharazmi, A

    1991-01-01

    Pseudomonas aeruginosa, an extracellular opportunistic pathogen, utilizes two major mechanisms to evade the host defence system. One of these mechanisms is the production of a large number of extracellular products, such as proteases, toxins, and lipases. The two proteases, alkaline protease and ...

  4. The evolutionary psychology of hunger.

    Science.gov (United States)

    Al-Shawaf, Laith

    2016-10-01

    An evolutionary psychological perspective suggests that emotions can be understood as coordinating mechanisms whose job is to regulate various psychological and physiological programs in the service of solving an adaptive problem. This paper suggests that it may also be fruitful to approach hunger from this coordinating mechanism perspective. To this end, I put forward an evolutionary task analysis of hunger, generating novel a priori hypotheses about the coordinating effects of hunger on psychological processes such as perception, attention, categorization, and memory. This approach appears empirically fruitful in that it yields a bounty of testable new hypotheses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    Science.gov (United States)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  6. Swarming mechanisms in the yellow fever mosquito: aggregation pheromones involved in the mating behavior of Aedes aegypti

    Science.gov (United States)

    Mosquitoes of various species mate in swarms comprised of tens to thousands flying males. Yet little information is known about mosquito swarming mechanism. Discovering chemical cues involved in mosquito biology leads to better adaptation of disease control interventions. In this study, we aimed ...

  7. Molecular mechanism for the involvement of nuclear receptor FXR in HBV-associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yong-dong Niu

    2011-08-01

    Full Text Available Farnesoid X receptor (FXR, also termed nuclear receptor NR1H4 is critically involved in the regulation of nascent bile formation and bile acid enterohepatic circulation. FXR and bile acids have been shown to play roles in liver regeneration and inflammatory responses. There is increasing evidence suggesting that FXR and the FXR signaling pathway are involved in the pathophysiology of a wide range of liver diseases, such as viral hepatitis, cirrhosis, and hepatocellular carcinoma (HCC. Here we discuss the latest discoveries of FXR functions with relevance to bile acid metabolism and HBV-associated HCC. More specifically, the goal of this review is to discuss the roles of FXR and bile acids in regulating HBV replication and how disregulation of the FXR-bile acid signaling pathway is involved in HBV-associated hepatocarcinogenesis.

  8. Evolutionary modelling of transitions to sustainable development

    International Nuclear Information System (INIS)

    Safarzynska, K.

    2010-01-01

    This thesis has examined how evolutionary economics can contribute to modelling the micromechanisms that underlie transitions towards sustainable development. In general, transitions are fundamental or structural system changes. They involve, or even require, escaping lock-in of dominant, environmentally unsustainable technologies, introducing major technical or social innovations, and changing prevailing social practices and structures. Due to the complexity of socioeconomic interactions, it is not always possible to identify, and thus target with appropriate policy instruments, causes of specific unsustainable patterns of behaviour. Formal modelling exercises can help improve our understanding of the interaction of various transition mechanisms which are otherwise difficult to grasp intuitively. They allow exploring effects of policy interventions in complex systems. However, existing models of transitions focus on social phenomena and seldom address economic problems. As opposed, mainstream (neoclassical) economic models of technological change do not account for social interactions, and changing heterogeneity of users and their perspectives - even though all of these can influence the direction of innovations and patterns of socio-technological development. Evolutionary economics offers an approach that goes beyond neoclassical economics - in the sense of employing more realistic assumptions regarding the behaviour and heterogeneity of consumers, firms and investors. It can complement current transition models by providing them with a better understanding of associated economic dynamics. In this thesis, formal models were proposed to illustrate the usefulness of a range of evolutionary-economic techniques for modelling transitions. Modelling exercises aimed to explain the core properties of socio-economic systems, such as lock-in, path-dependence, coevolution, group selection and recombinant innovation. The studies collected in this dissertation illustrate that

  9. Toward an evolutionary-predictive foundation for creativity : Commentary on "Human creativity, evolutionary algorithms, and predictive representations: The mechanics of thought trials" by Arne Dietrich and Hilde Haider, 2014 (Accepted pending minor revisions for publication in Psychonomic Bulletin & Review).

    Science.gov (United States)

    Gabora, Liane; Kauffman, Stuart

    2016-04-01

    Dietrich and Haider (Psychonomic Bulletin & Review, 21 (5), 897-915, 2014) justify their integrative framework for creativity founded on evolutionary theory and prediction research on the grounds that "theories and approaches guiding empirical research on creativity have not been supported by the neuroimaging evidence." Although this justification is controversial, the general direction holds promise. This commentary clarifies points of disagreement and unresolved issues, and addresses mis-applications of evolutionary theory that lead the authors to adopt a Darwinian (versus Lamarckian) approach. To say that creativity is Darwinian is not to say that it consists of variation plus selection - in the everyday sense of the term - as the authors imply; it is to say that evolution is occurring because selection is affecting the distribution of randomly generated heritable variation across generations. In creative thought the distribution of variants is not key, i.e., one is not inclined toward idea A because 60 % of one's candidate ideas are variants of A while only 40 % are variants of B; one is inclined toward whichever seems best. The authors concede that creative variation is partly directed; however, the greater the extent to which variants are generated non-randomly, the greater the extent to which the distribution of variants can reflect not selection but the initial generation bias. Since each thought in a creative process can alter the selective criteria against which the next is evaluated, there is no demarcation into generations as assumed in a Darwinian model. We address the authors' claim that reduced variability and individuality are more characteristic of Lamarckism than Darwinian evolution, and note that a Lamarckian approach to creativity has addressed the challenge of modeling the emergent features associated with insight.

  10. Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

    DEFF Research Database (Denmark)

    List, K; Høyer-Hansen, G; Rønne, E

    1999-01-01

    Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance or interfer......Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance......) can be employed as a highly useful tool to characterize the inhibitory mechanism of specific antagonist antibodies. Two inhibitory antibodies against uPAR, mAb R3 and mAb R5, were shown to exhibit competitive and non-competitive inhibition, respectively, of ligand binding to the receptor. The former...

  11. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Science.gov (United States)

    Sandi, Carmen

    1998-01-01

    Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules. PMID:9920681

  12. Evolutionary foundations for cancer biology.

    Science.gov (United States)

    Aktipis, C Athena; Nesse, Randolph M

    2013-01-01

    New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles-cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations-provide a foundation for understanding, preventing, and treating cancer.

  13. Up-date on neuro-immune mechanisms involved in allergic and non-allergic rhinitis

    NARCIS (Netherlands)

    van Gerven, L.; Boeckxstaens, G.; Hellings, P.

    2012-01-01

    Non-allergic rhinitis (NAR) is a common disorder, which can be defined as chronic nasal inflammation, independent of systemic IgE-mediated mechanisms. Symptoms of NAR patients mimic those of allergic rhinitis (AR) patients. However, AR patients can easily be diagnosed with skin prick test or

  14. Understanding the molecular mechanisms involved in the interfacial self-healing of supramolecular rubbers

    NARCIS (Netherlands)

    Bose, R.K.; Garcia Espallargas, S.J.; Van der Zwaag, S.

    2013-01-01

    Supramolecular rubbers based on 2-aminoethylimidazolidone and fatty acids with epoxy crosslinks have been shown to self-heal via multiple hydrogen bonding sites. In this work, several tools are used to investigate the molecular mechanisms taking place at the interface to understand cohesive healing

  15. Nitric oxide is involved in the down-regulation of sost expression induced by mechanical loading

    NARCIS (Netherlands)

    Delgado-Calle, J.; Riancho, J.A.; Klein-Nulend, J.

    2014-01-01

    Mechanical stimulation reduces sclerostin expression in rodents. However, few data are available about the effect of physical stimuli in human systems. Recently we observed that the demethylating agent AzadC induces SOST expression in bone cells. This allowed us in this study to explore the effect

  16. "Coding" and "Decoding": hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis.

    Science.gov (United States)

    Zhang, Xu; Wang, Fengshan; Sheng, Juzheng

    2016-06-16

    Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Study of mechanism involved in synthesis of graphene oxide and reduced graphene oxide from graphene nanoplatelets

    Science.gov (United States)

    Sharma, Bhasha; Shekhar, Shashank; Malik, Parul; Jain, Purnima

    2018-06-01

    Graphene, a wonder material has inspired quest among researchers due to its numerous applications and exceptional properties. This paper highlights the mechanism and chemistry behind the fabrication of graphene oxide by using phosphoric acid. Chemical functionalization is of prime importance which avoids agglomeration of nanoparticles to attain inherent properties. As non-homogeneous dispersion limits its utilization due to interfacial interactions which restrict reactive sites to produce intercalated network. Thus, chemically functionalized graphene leads to stable dispersion and enhances thermal, mechanical and electrical properties of the resultant polymer composite materials. Solubility of graphene in aqueous solution is the major issue because graphene is hydrophobic, to rectify this oxygen containing hydrophilic groups must be introduced to make it compatible and this can be attained by covalent functionalization. Among all nanofiller GO has shown average particle size i.e. 95 nm and highest surface charge density. The characteristic changes were estimated using Raman spectra.

  18. Involvement of epigenetic mechanisms in the development of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Tomaž Zupanc

    2012-03-01

    victims with no childhood abuse were found. It was suggested that changes in glucocorticoid system are mediated by tissue-specific changes in gene expression. Recent studies suggest that epigenetic mechanisms may play an important role in the interplay between stress exposure and genetic vulnerability. Conclusions: Integrating epigenetics into a model that permits prior experience to have a central role in determining individual differences is also consistent with a developmental perspective of PTSD vulnerability.

  19. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Grover

    2013-01-01

    Full Text Available Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms.

  20. Phenanthrene causes ocular developmental toxicity in zebrafish embryos and the possible mechanisms involved

    International Nuclear Information System (INIS)

    Huang, Lixing; Wang, Chonggang; Zhang, Youyu; Wu, Meifang; Zuo, Zhenghong

    2013-01-01

    Highlights: • Phe exposure caused obvious morphological changes in the retina. • Phe exposure caused apoptosis and reduction of cell proliferation in the retina. • Phe causes ocular toxicity might be via the AhR/Zeb1/Mitf/Pax6 signaling pathway. • AhR is a repressor of Zeb1. -- Abstract: Recent studies show that polycyclic aromatic hydrocarbons (PAHs) may be a candidate cause of developmental defects of the retina, but the mechanism is still unclear. We evaluated the mechanism(s) underlying PAH-induced retinal development defects due to exposure to environmental concentrations of Phenanthrene (Phe) in zebrafish. We found that exposure to environmental concentrations of Phe caused obvious morphological changes, developmental retardation, apoptosis, and reduction of cell proliferation in the retina. Our results indicated that Phe could cause visual system developmental defects. Phe exposure up-regulated aryl hydrocarbon receptor (AhR) and microphthalmia-associated transcription factor (Mtif) expression, and down-regulated zinc finger E-box binding homeobox 1 (Zeb1) and paired box 6 (Pax6). Moreover, we demonstrated that AhR was a repressor of Zeb1. We propose that Phe's ocular toxicity is mediated by up-regulating AhR, which then down-regulates Zeb1, in turn inducing Mitf expression while inhibiting Pax6 expression

  1. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

    Science.gov (United States)

    Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

    2012-06-28

    Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A.

    Science.gov (United States)

    Harrison, E H; Hussain, M M

    2001-05-01

    Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme, pancreatic triglyceride lipase (PTL), and intestinal brush border enzyme, phospholipase B. Recent work on the carboxylester lipase (CEL) knockout mouse suggests that CEL may not be involved in dietary retinyl ester digestion. The possible roles of the pancreatic lipase-related proteins (PLRP) 1 and 2 and other enzymes require further investigation. Unesterified retinol is taken up by the enterocytes, perhaps involving both diffusion and protein-mediated facilitated transport. Once in the cell, retinol is complexed with cellular retinol-binding protein type 2 (CRBP2) and the complex serves as a substrate for reesterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). Retinol not bound to CRBP2 is esterified by acyl-CoA acyltransferase (ARAT). The retinyl esters are incorporated into chylomicrons, intestinal lipoproteins that transport other dietary lipids such as triglycerides, phospholipids, and cholesterol. Chylomicrons containing newly absorbed retinyl esters are then secreted into the lymph.

  3. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  4. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    International Nuclear Information System (INIS)

    Pruett, Stephen B.; Fan, Ruping; Zheng, Qiang

    2006-01-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S - group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD

  5. A novel mechanism of P-type ATPase autoinhibition involving both termini of the protein

    DEFF Research Database (Denmark)

    Ekberg, Kira; Palmgren, Michael; Veierskov, Bjarke

    2010-01-01

    The activity of many P-type ATPases is found to be regulated by interacting proteins or autoinhibitory elements located in N- or C-terminal extensions. An extended C terminus of fungal and plant P-type plasma membrane H+-ATPases has long been recognized to be part of a regulatory apparatus....... This identifies the first group of P-type ATPases for which both ends of the polypeptide chain constitute regulatory domains, which together contribute to the autoinhibitory apparatus. This suggests an intricate mechanism of cis-regulation with both termini of the protein communicating to obtain the necessary...

  6. A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation

    Directory of Open Access Journals (Sweden)

    Jelena Ostojić

    2014-01-01

    Full Text Available Mitochondria are essential organelles that are central to a multitude of cellular processes, including oxidative phosphorylation (OXPHOS, which produces most of the ATP in animal cells. Thus it is important to understand not only the mechanisms and biogenesis of this energy production machinery but also how it is regulated in both physiological and pathological contexts. A recent study by Ostojić et al. [Cell Metabolism (2013 18, 567-577] has uncovered a regulatory loop by which the biogenesis of a major enzyme of the OXPHOS pathway, the respiratory complex III, is coupled to the energy producing activity of the mitochondria.

  7. Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

    Directory of Open Access Journals (Sweden)

    Yuan Jiang

    2014-03-01

    Full Text Available Objective: To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZon glioblastoma cell strain. Methods: MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while flow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS level while Real-time PCR and Western blot tests were applied to determine the influence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efficacy of TMZ.

  8. Mechanisms Involved in Secondary Cardiac Dysfunction in Animal Models of Trauma and Hemorrhagic Shock.

    Science.gov (United States)

    Wilson, Nick M; Wall, Johanna; Naganathar, Veena; Brohi, Karim; De'Ath, Henry D

    2017-10-01

    Clinical evidence reveals the existence of a trauma-induced secondary cardiac injury (TISCI) that is associated with poor patient outcomes. The mechanisms leading to TISCI in injured patients are uncertain. Conversely, animal models of trauma hemorrhage have repeatedly demonstrated significant cardiac dysfunction following injury, and highlighted mechanisms through which this might occur. The aim of this review was to provide an overview of the animal studies describing TISCI and its pathophysiology.Basic science models of trauma show evidence of innate immune system activation via Toll-like receptors, the exact protagonists of which remain unclear. Shortly following trauma and hemorrhage, cardiomyocytes upregulate gene regulatory protein and inflammatory molecule expression including nuclear factor kappa beta, tumor necrosis factor alpha, and interleukin-6. This is associated with expression of membrane bound adhesion molecules and chemokines leading to marked myocardial leukocyte infiltration. This cell activation and infiltration is linked to a rise in enzymes that cause oxidative and nitrative stress and subsequent protein misfolding within cardiomyocytes. Such protein damage may lead to reduced contractility and myocyte apoptosis. Other molecules have been identified as cardioprotective following injury. These include p38 mitogen-activated protein kinases and heat shock proteins.The balance between increasing damaging mediators and a reduction in cardio-protective molecules appears to define myocardial function following trauma. Exogenous therapeutics have been trialled in rodents with promising abilities to favorably alter this balance, and subsequently lead to improved cardiac function.

  9. Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

    Science.gov (United States)

    Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

    2016-12-01

    While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.

  10. Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

    Science.gov (United States)

    Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

    2016-12-01

    This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

  11. Application of microscopy methods to the understanding of mechanisms involved in ilmenite reduction by hydrogen

    International Nuclear Information System (INIS)

    De Vries, M.; Grey, I.; Fitzgerald, J.

    2003-01-01

    Full text: Titania pigment is one of the major drivers of the mineral sands industry with production of over 4 million tpa in 2002 for paints, plastics, paper and ceramics applications. The main feedstock for titania pigment production is ilmenite, FeTiO 3 . It is used either directly or after it has been upgraded to a higher titania content. The major commercial upgrading processes are electro smelting (titania slag) or high temperature char reduction followed by iron removal (synthetic rutile SR). Future ilmenite upgrading processes are likely to use low temperature hydrogen reduction according to reaction, followed by aeration of the metallic iron and acid leaching to produce a high grade SR (Nicholson et al, 2000). The commercial application of such a process requires a detailed knowledge of the kinetics of reaction. FeTiO 3 + H 2 = Fe(m) + TiO 2 + H 2 O. The kinetics of ilmenite reduction has been studied at CSIRO Minerals using a specially designed thermogravimetric apparatus built around a Cahn pressurised symmetrical beam balance. The kinetics have been measured as a function of different operating parameters such as temperature, gas velocity and pressure. The parameters were set so as to minimise mass transport effects and increase chemical reaction control and to ensure the reduction kinetics are outside the gas starvation region. Small samples were used that had been sintered at close to melting point to form large grains with low unconnected porosity. High flow rates of reactant gas were also used. The application of a range of microscopy techniques to the reduced samples at various stages of reaction conversion has been critical to the development of an understanding of the reaction mechanisms. From analysis of TEM, IFESEM and optical microscopy results it appears that initially, chemical reaction is rate controlling at the surface and as the reaction proceeds topochemically inwards then diffusion mechanisms increase their control. Reaction proceeds

  12. Some mechanisms involved in the radiosensitization of E. coli B/r by paracetamol

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, M A; Gopalakrishna, K [Bhabha Atomic Research Centre, Bombay (India). Biology and Agriculture Div.

    1977-06-01

    Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to /sup 60/Co gamma rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining.

  13. Some mechanisms involved in the radiosensitization of E.coli B/r by paracetamol

    International Nuclear Information System (INIS)

    Shenoy, M.A.; Gopalakrishna, K.

    1977-01-01

    Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to 60 Co gamma-rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining. (author)

  14. Attractive evolutionary equilibria

    NARCIS (Netherlands)

    Joosten, Reinoud A.M.G.; Roorda, Berend

    2011-01-01

    We present attractiveness, a refinement criterion for evolutionary equilibria. Equilibria surviving this criterion are robust to small perturbations of the underlying payoff system or the dynamics at hand. Furthermore, certain attractive equilibria are equivalent to others for certain evolutionary

  15. Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function.

    Science.gov (United States)

    Tsigelny, Igor F; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K

    2008-10-01

    Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane alpha-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family--the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY)--have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational "switching" mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible "switch" mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.(23) We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a "tilt" of 9 degrees -10 degrees rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the "tilted" structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while the

  16. Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

    Directory of Open Access Journals (Sweden)

    Sheila G Crewther

    Full Text Available Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/-10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5 mM Ba(2+ and 10(-5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba(2+ but significant change only for negative lens defocus with bumetanide (Rx(SAL(-10D = -8.6 +/- .9 D; Rx(Ba2+(-10D = -2.9 +/- .9 D; Rx(Bum(-10D = -2.9 +/- .9 D; Rx(SAL(+10D = +8.2 +/- .9 D; Rx(Ba2+(+10D = +2.8 +/- 1.3 D; Rx(Bum(+10D = +8.0 +/- .7 D. Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba(2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a

  17. Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

    Science.gov (United States)

    Stepanovic-Petrovic, Radica M; Tomic, M A; Vuckovic, S M; Ugresic, N D; Prostran, M S; Boskovic, B

    2007-04-01

    The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

  18. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system.

    Science.gov (United States)

    Kibria, Golam; Hatakeyama, Hiroto; Harashima, Hideyoshi

    2014-01-01

    Multidrug resistance (MDR), the principal mechanism by which many cancers develop resistance to chemotherapy, is one of the major obstacles to the successful clinical treatment of various types of cancer. Several key regulators are responsible for mediating MDR, a process that renders chemotherapeutic drugs ineffective in the internal organelles of target cells. A nanoparticulate drug delivery system (DDS) is a potentially promising tool for circumventing such MDR, which can be achieved by targeting tumor cells themselves or tumor endothelial cells that support the survival of MDR cancer cells. The present article discusses key factors that are responsible for MDR in cancer cells, with a specific focus on the application of DDS to overcome MDR via the use of chemotherapy or macromolecules.

  19. Anticonvulsants Teratogenic Mechanism Involves Alteration of Bioelectrically-controlled Processes in the Embryo. A hypothesis

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-01-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations is controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. If our theory were correct, development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. PMID:24815983

  20. Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Golan Hava

    2004-04-01

    Full Text Available Abstract Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.

  1. Mechanisms involved in growth inhibition induced by clofibrate in hepatoma cells

    International Nuclear Information System (INIS)

    Muzio, Giuliana; Maggiora, Marina; Trombetta, Antonella; Martinasso, Germana; Reffo, Patrizia; Colombatto, Sebastiano; Canuto, Rosa Angela

    2003-01-01

    Low concentrations of some peroxisome proliferators have been found to decrease apoptosis in rat liver cells, whereas higher but pharmacological concentrations have been found to inhibit cell proliferation or to induce apoptosis in human and rat hepatoma cells. The highly deviated JM2 rat hepatoma cell line was used to examine the mechanisms underlying the inhibitory effect on cell proliferation. Clofibrate chiefly inhibited cell proliferation in these cells. Parallel to the decrease in cell proliferation there was an increase of peroxisome proliferator activated receptor (PPAR) gamma and of protein phosphatase 2A, whose importance was confirmed, respectively, by using antisense oliginucleotides (AS-ODN) or okadaic acid. The increase of protein phosphatase 2A induced by PPARgamma caused a decrease of MAPK, an intracellular signaling transduction pathway, as shown by evaluation of Erk1,2 and c-myc. In light of these results, clofibrate, like conventional synthetic ligands of PPARgamma, may be regarded as a possible prototype anti-tumour drug

  2. Mechanisms Involved in Thromboxane A2-induced Vasoconstriction of Rat Intracavernous Small Penile Arteries

    DEFF Research Database (Denmark)

    Grann, Martin; Comerma Steffensen, Simon Gabriel; Arcanjo, Daniel Dias Rufino

    2015-01-01

    relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca2+ influx through L-type and TRP channels, and ROCKdependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated......Diabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated...... the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca2+]i) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619...

  3. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

    Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

  4. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Alline C. Campos

    2017-05-01

    Full Text Available Beneficial effects of cannabidiol (CBD have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.

  5. Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat

    International Nuclear Information System (INIS)

    Takahashi, Akihisa; Ohnishi, Takeo

    2009-01-01

    Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat. (author)

  6. Effects of high fluoride intake on child mental work capacity: preliminary investigation into the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Li, X.J.; Wei, S.Q. [Child & Adolescent Hygiene Teaching Research Station, Chengdu (China)

    2008-10-15

    A study was carried out on 157 children, age 12-13, from a coal-burning fluorosis endemic area together with an experiment looking into the effect of high fluoride intake in animals. The results showed that early, prolonged high fluoride intake causes a decrease in a child's mental work capacity and that prolonged high uptake of fluoride causes a child's levels of hair zinc to drop. A multifactoral correlative analysis demonstrated a direct correlation between hair zinc and mental work capacity. The decrease of 5-hydroxyindoleacetic acid and the increase of norepinephrine in animal brains exposed to high levels of fluoride suggest a possible mechanism for mental work capacity deficits in children. However, further research is necessary.

  7. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Directory of Open Access Journals (Sweden)

    Yidan Ma

    Full Text Available A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  8. Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway.

    Science.gov (United States)

    Ha, Ae Wha; Kim, Woo Kyoung

    2017-06-01

    Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly ( P concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly ( P antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

  9. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Science.gov (United States)

    Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

    2015-01-01

    A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  10. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women

    Science.gov (United States)

    Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

    2015-01-01

    A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed. PMID:26309232

  11. Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.

    Science.gov (United States)

    Delivanis, Danae A; Gustafson, Michael P; Bornschlegl, Svetlana; Merten, Michele M; Kottschade, Lisa; Withers, Sarah; Dietz, Allan B; Ryder, Mabel

    2017-08-01

    Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. Single-center, retrospective cohort study. We studied 93 patients with advanced cancer (ages 24 to 82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed. Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in seven patients (54%), from which four recovered. New onset of hypothyroidism overt/subclinical developed in three patients. Levothyroxine dosing required doubling in three patients with a known history of hypothyroidism. Thyroperoxidase antibodies were positive in the minority of the patients [4/13 (31%)] and diffuse increased 18fludeoxyglucose uptake of the thyroid gland was observed in the majority [7/11 (64%)] of patients. We observed more circulating CD56+CD16+ natural killer (NK) cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1-treated patients. Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment. Copyright © 2017 Endocrine Society

  12. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  13. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

    Directory of Open Access Journals (Sweden)

    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  14. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General Article Volume 21 Issue 9 September 2016 pp 803- ... Keywords. Evolutionary game theory, evolutionary stable state, conflict, cooperation, biological games.

  15. Study of the physical mechanisms involved in the femtosecond laser optical breakdown of dielectric materials

    International Nuclear Information System (INIS)

    Mouskeftaras, Alexandros

    2013-01-01

    We have carried out detailed time resolved experimental studies of the mechanism of electron excitation-relaxation, when an ultrashort (60 fs -1 ps) laser (UV and IR) pulse interacts with a wide band gap dielectric material. The studies cover a range of different dielectric materials and the investigated regimes span from nondestructive ionization of the material at the low power end (∼TW/cm 2 ) to ablative domain at a higher laser power (∼10 TW/cm 2 ). This gives fundamental insight into the understanding of the laser damaging process taking place under our irradiation conditions. The usage of time-resolved spectral interferometry technique allows to directly measure the electron density of the irradiated material under different excitation conditions and hence leads to quantification of the process. The measurements, carried out at the optical breakdown threshold utilizing different pulse durations, raise questions regarding the usage of critical excitation density as a universal ablation criterion. A new criterion related to the exchanged energy is proposed. Additionally, the use of an experimental setup implementing a double pump pulse allows the identification of different excitation mechanisms taking place at time scales of the order of the pulse duration used. Electronic avalanche is observed in some materials (SiO 2 , NaCl) while this is not the case for others (Al 2 O 3 , MgO). These differences are discussed in detail. Next, we measure the energy spectrum of excited electrons with a complementary technique: the photoemission spectroscopy. These results allow us on one hand to show a crossed effect between the two 'pump' pulses and on the other hand to measure electron relaxation characteristic times, as a function of their kinetic energy. Finally, a morphological study of craters resulting from ablation in the case of a single pulse has been carried out for different irradiation parameters: number of shots, energy and pulse duration. This work has

  16. Flavonoids Active Against Osteosarcoma: A Review of the Molecular Mechanisms Involved.

    Science.gov (United States)

    Liu, Hui; Gao, Yutong; Dong, Yonghui; Cheng, Peng; Chen, Anmin; Huang, Hui

    2017-01-01

    Osteosarcoma is the most frequent primitive malignant bone tumor affecting adolescents and young adults worldwide. The tumor exhibits aggressive growth in the primary site and readily metastasizes to other organs. There has been no significant improvement in the 5-year survival rate since the 1970s and the figure remains at 60-70%. In addition, the side effects of chemotherapeutic drugs and resistance to chemotherapy compromise the effects of treatment for osteosarcoma. In recent years, the development of flavonoids drugs inhibiting carcinogenesis is attracting great interest in the scientific community. Flavonoids are one kind of polyphenolic compounds widely found in vegetables and fruits. Moreover, flavonoids have become popular compounds, exhibiting comprehensive antitumor activities, while being safe and inexpensive. Here, the literature on the benefits afforded by flavonoids in terms of osteosarcoma treatment is reviewed and certain flavonoids and their effects on osteosarcoma are discussed. These compounds can perturb the cell cycle, induce apoptosis, inhibit tumor cell invasion and metastasis, potentiate the actions of chemotherapeutic agents, trigger autophagy, and stimulate antitumor activity in vivo. In summary, we highlight the currently well-accepted flavonoid compounds and detail the molecular mechanisms by which flavonoids may treat osteosarcoma, and thus the flavonoids exhibit great promise as anti-osteosarcoma agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Chemical compounds and mechanisms involved in the formation and stabilization of foam in sparkling wines.

    Science.gov (United States)

    Kemp, Belinda; Condé, Bruna; Jégou, Sandrine; Howell, Kate; Vasserot, Yann; Marchal, Richard

    2018-02-08

    The visual properties of sparkling wine including foam and bubbles are an indicator of sparkling wine quality. Foam properties, particularly foam height (FH) and foam stability (TS), are significantly influenced by the chemical composition of the wine. This review investigates our current knowledge of specific chemical compounds and, the mechanisms by which they influence the foam properties of sparkling wines. Grape and yeast proteins, amino acids, polysaccharides, phenolic compounds, organic acids, fatty acids, ethanol and sugar are examined with respect to their contribution to foam characteristics in sparkling wines made with the Traditional, Transfer, and Charmat and carbonation methods. Contradictory results have been identified that appear to be due to the analytical methods used to measure and quantify compounds and foam. Biopolymer complexes are discussed and absent knowledge with regards to thaumatin-like proteins (TLPs), polysaccharides, amino acids, oak-derived phenolic compounds and organic acids are identified. Future research is also likely to concentrate on visual analysis of sparkling wines by in-depth imaging analysis and specific sensory analysis techniques.

  18. Studies of the mechanisms involved in the laser surface hardening process of aluminum base alloys

    International Nuclear Information System (INIS)

    Silva, Luciana Ventavele da

    2011-01-01

    The Al-Si alloys are widely used in industry to replace the steel and gray cast iron in high-tech sectors. The commercial importance of these alloys is mainly due to its low weight, excellent wear (abrasion) and corrosion resistance, high resistance at elevated temperatures, low coefficient of thermal expansion and lesser fuel consumption that provide considerable reduction of emission of pollutants. In this work, Al-Si alloy used in the automotive industry to manufacture pistons of internal combustion engines, was undergone to surface treatments using LASER remelting (Nd:YAG, λ = 1.06 μm, pulsed mode). The LASER enables various energy concentrations with accurate transfer to the material without physical contact. The intense energy transfer causes the occurrence of structural changes in the superficial layer of the material. Experiments with single pulses and trails were conducted under various conditions of LASER processing in order to analyze microstructural changes resulting from treatments and their effects on the hardness. For the characterization of hardened layer was utilized the following techniques: optical microscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), x-ray mapping, Vickers microhardness and maximum roughness tests. The high cooling rate caused a change in the alloy structure due to the refinement of the primary eutectic silicon particles, resulting in increase of the mechanical properties (hardness) of the Al-Si alloy. (author)

  19. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis.

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; Reis, Vitor Manoel Silva Dos

    2018-03-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

  20. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis*

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; dos Reis, Vitor Manoel Silva

    2018-01-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation. PMID:29723367

  1. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    Directory of Open Access Journals (Sweden)

    M.P. da Silva

    2014-02-01

    Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  2. Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration.

    Science.gov (United States)

    Sakamoto, Kazuhiro; Matsumura, Shigenobu; Okafuji, Yoko; Eguchi, Ai; Lee, Shinhye; Adachi, Shin-ichi; Fujitani, Mina; Tsuzuki, Satoshi; Inoue, Kazuo; Fushiki, Tohru

    2015-01-01

    High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.

  3. Mechanism of phytohormone involvement in feedback regulation of cotton leaf senescence induced by potassium deficiency.

    Science.gov (United States)

    Wang, Ye; Li, Bo; Du, Mingwei; Eneji, A Egrinya; Wang, Baomin; Duan, Liusheng; Li, Zhaohu; Tian, Xiaoli

    2012-10-01

    To elucidate the phytohormonal basis of the feedback regulation of leaf senescence induced by potassium (K) deficiency in cotton (Gossypium hirsutum L.), two cultivars contrasting in sensitivity to K deficiency were self- and reciprocally grafted hypocotyl-to-hypocotyl, using standard grafting (one scion grafted onto one rootstock), Y grafting (two scions grafted onto one rootstock), and inverted Y grafting (one scion grafted onto two rootstocks) at the seedling stage. K deficiency (0.03mM for standard and Y grafting, and 0.01mM for inverted Y grafting) increased the root abscisic acid (ABA) concentration by 1.6- to 3.1-fold and xylem ABA delivery rates by 1.8- to 4.6-fold. The K deficiency also decreased the delivery rates of xylem cytokinins [CKs; including the zeatin riboside (ZR) and isopentenyl adenosine (iPA) type] by 29-65% and leaf CK concentration by 16-57%. The leaf ABA concentration and xylem ABA deliveries were consistently greater in CCRI41 (more sensitive to K deficiency) than in SCRC22 (less sensitive to K deficiency) scions under K deficiency, and ZR- and iPA-type levels were consistently lower in the former than in the latter, irrespective of rootstock cultivar or grafting type, indicating that cotton shoot influences the levels of ABA and CKs in leaves and xylem sap. Because the scions had little influence on phytohormone levels in the roots (rootstocks) of all three types of grafts and rootstock xylem sap (collected below the graft union) of Y and inverted Y grafts, it appears that the site for basipetal feedback signal(s) involved in the regulation of xylem phytohormones is the hypocotyl of cotton seedlings. Also, the target of this feedback signal(s) is more likely to be the changes in xylem phytohormones within tissues of the hypocotyl rather than the export of phytohormones from the roots.

  4. Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review

    Directory of Open Access Journals (Sweden)

    Aïsha Sahaï

    2017-10-01

    Full Text Available Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.

  5. Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement.

    Science.gov (United States)

    Farrero, Eva; Prats, Enric; Povedano, Mónica; Martinez-Matos, J Antonio; Manresa, Frederic; Escarrabill, Joan

    2005-06-01

    To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). Retrospective study in a tertiary care referral center. HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002). Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

  6. Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats

    Directory of Open Access Journals (Sweden)

    Yano Takahisa

    2011-01-01

    Full Text Available Abstract Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol and memantine (1 μmol, NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t. and ifenprodil (50 mg/kg, p.o. significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase but not on Day 5 (early phase. Moreover, we examined the involvement of nitric oxide synthase (NOS as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

  7. Molecular mechanisms of drug resistance and tumor promotion involving mammalian ribonucleotide reductase

    Energy Technology Data Exchange (ETDEWEB)

    Choy, B.B.K.

    1991-01-01

    Mammalian ribonucleotide reductase is a highly regulated, rate-limiting activity responsible for converting ribonucleoside diphosphates to the deoxyribonucleotide precursors of DNA. The enzyme consists of two nonidentical proteins called M1 and M2, both of which are required for activity. Hydroxyurea is an antitumor agent which inhibits ribonucleotide reductase by interacting with the M2 component specifically at a unique tyrosyl free radical. Studies were conducted on a series of drug resistant mouse cell lines, selected by a step-wise procedure for increasing levels of resistance to the cytotoxic effects of hydroxyurea. Each successive drug selection step leading to the isolation of highly resistant cells was accompanied by stable elevations in cellular resistance and ribonucleotide reductase activity. The drug resistant cell lines exhibited gene amplification of the M2 gene, elevated M2 mRNA, and M2 protein. In addition to M2 gene amplification, posttranscriptional modulation also occurred during the drug selection. Studies of the biosynthesis rates with exogenously added iron suggest a role for iron in regulating the level of M2 protein when cells are cultured in the presence of hydroxyurea. The hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron centre, which readily releases iron. Altered expression of ferritin appears to be required for the development of hydroxyurea resistance in nammalian cells. The results show an interesting relationship between the expressions of ribonucleotide reductase and ferritin. The phorbol ester tumor promoter, TPA, is also able to alter the expression of M2. TPA was able to induce M2 mRNA levels transiently up to 18-fold within 1/2 hour. This rapid and large elevation of ribonucleotide reductase suggests that the enzyme may play a role in tumor promotion. Studies of the M2 promoter region were undertaken to better understand the mechanism of TPA induction of M2.

  8. Physiological and Molecular Mechanism of Nitric Oxide (NO Involved in Bermudagrass Response to Cold Stress.

    Directory of Open Access Journals (Sweden)

    Jibiao Fan

    Full Text Available Bermudagrass is widely utilized in parks, lawns, and golf courses. However, cold is a key factor limiting resource use in bermudagrass. Therefore, it is meaningful to study the mechanism of bermudagrass response to cold. Nitric oxide (NO is a crucial signal molecule with multiple biological functions. Thus, the objective of this study was to investigate whether NO play roles in bermudagrass response to cold. Sodium nitroprusside (SNP was used as NO donor, while 2-phenyl-4,4,5,5-tetramentylimidazoline-l-oxyl-3-xide (PTIO plus NG-nitro-L-arginine methyl ester (L-NAME were applied as NO inhibitor. Wild bermudagrass was subjected to 4 °C in a growth chamber under different treatments (Control, SNP, PTIO + L-NAME. The results indicated lower levels of malondialdehyde (MDA content and electrolyte leakage (EL, higher value for chlorophyll content, superoxide dismutase (SOD and peroxidase (POD activities after SNP treatment than that of PTIO plus L-NAME treatments under cold stress. Analysis of Chlorophyll (Chl a fluorescence transient displayed that the OJIP transient curve was higher after treatment with SNP than that of treated with PTIO plus L-NAME under cold stress. The values of photosynthetic fluorescence parameters were higher after treatment with SNP than that of treated with PTIO plus L-NAME under cold stress. Expression of cold-responsive genes was altered under cold stress after treated with SNP or PTIO plus L-NAME. In summary, our findings indicated that, as an important strategy to protect bermudagrass against cold stress, NO could maintain the stability of cell membrane, up-regulate the antioxidant enzymes activities, recover process of photosystem II (PSII and induce the expression of cold-responsive genes.

  9. Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E

    Directory of Open Access Journals (Sweden)

    Andréia T Santana

    2015-01-01

    Full Text Available BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp. that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10: DMSO/ saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididy-mal sperm count was observed (P 0.05. The levels of reduced glutathione and pyridine nucleotides in testis homogen-ate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05. Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01, a lipid peroxida-tion indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05. CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

  10. Mechanisms involved in the association between periodontitis and complications in pregnancy.

    Directory of Open Access Journals (Sweden)

    Marcela eYang

    2015-01-01

    Full Text Available The association between periodontitis and gestation complications such as premature delivery, low weight at birth and preeclampsia has been suggested. Nevertheless, epidemiological data have shown contradictory data, mainly due to differences in clinical parameters of periodontitis assessment. Furthermore, differences in microbial composition and immune response between aggressive and chronic periodontitis are not addressed by these epidemiological studies. We aimed to review the current data on the association between gestation complications and periodontitis, and the mechanisms underlying this association. Shifts in the microbial composition of the subgingival biofilm may occur during pregnancy, leading to a potentially more hazardous microbial community. Pregnancy is characterized by physiological immune tolerance. However, the infection leads to a shift in maternal immune response to a pathogenic pro-inflammatory response, with production of inflammatory cytokines and toxic products. In women with periodontitis, the infected periodontal tissues may act as reservoirs of bacteria and their products which can disseminate to the fetus-placenta unit. In severe periodontitis patients, the infection agents and their products are able to activate inflammatory signaling pathways locally and in extra-oral sites, including the placenta-fetal unit, which may not only induce preterm labor, but also lead to preeclampsia and restrict intrauterine growth. Despite these evidences, the effectiveness of periodontal treatment in preventing gestational complications was still not established since it may be influenced by several factors such as severity of disease, composition of microbial community, treatment strategy, and period of treatment throughout pregnancy. This lack of scientific evidence does not exclude the need to control infection and inflammation in periodontitis patients during pregnancy, and treatment protocols should be validated.

  11. Mechanisms Involved in the Association between Periodontitis and Complications in Pregnancy

    Science.gov (United States)

    Zi, Marcela Yang Hui; Longo, Priscila Larcher; Bueno-Silva, Bruno; Mayer, Marcia Pinto Alves

    2015-01-01

    The association between periodontitis and some of the problems with pregnancy such as premature delivery, low weight at birth, and preeclampsia (PE) has been suggested. Nevertheless, epidemiological data have shown contradictory data, mainly due to differences in clinical parameters of periodontitis assessment. Furthermore, differences in microbial composition and immune response between aggressive and chronic periodontitis are not addressed by these epidemiological studies. We aimed to review the current data on the association between some of these problems with pregnancy and periodontitis, and the mechanisms underlying this association. Shifts in the microbial composition of the subgingival biofilm may occur during pregnancy, leading to a potentially more hazardous microbial community. Pregnancy is characterized by physiological immune tolerance. However, the infection leads to a shift in maternal immune response to a pathogenic pro-inflammatory response, with production of inflammatory cytokines and toxic products. In women with periodontitis, the infected periodontal tissues may act as reservoirs of bacteria and their products that can disseminate to the fetus-placenta unit. In severe periodontitis patients, the infection agents and their products are able to activate inflammatory signaling pathways locally and in extra-oral sites, including the placenta-fetal unit, which may not only induce preterm labor but also lead to PE and restrict intrauterine growth. Despite these evidences, the effectiveness of periodontal treatment in preventing gestational complications was still not established since it may be influenced by several factors such as severity of disease, composition of microbial community, treatment strategy, and period of treatment throughout pregnancy. This lack of scientific evidence does not exclude the need to control infection and inflammation in periodontitis patients during pregnancy, and treatment protocols should be validated. PMID:25688342

  12. Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

    Science.gov (United States)

    Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

    2011-01-01

    Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

  13. Complexity in Evolutionary Processes

    International Nuclear Information System (INIS)

    Schuster, P.

    2010-01-01

    Darwin's principle of evolution by natural selection is readily casted into a mathematical formalism. Molecular biology revealed the mechanism of mutation and provides the basis for a kinetic theory of evolution that models correct reproduction and mutation as parallel chemical reaction channels. A result of the kinetic theory is the existence of a phase transition in evolution occurring at a critical mutation rate, which represents a localization threshold for the population in sequence space. Occurrence and nature of such phase transitions depend critically on fitness landscapes. The fitness landscape being tantamount to a mapping from sequence or genotype space into phenotype space is identified as the true source of complexity in evolution. Modeling evolution as a stochastic process is discussed and neutrality with respect to selection is shown to provide a major challenge for understanding evolutionary processes (author)

  14. Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: mechanism involved.

    Science.gov (United States)

    Liu, Lu; Feng, Guo-Sheng; Gao, Hong; Tong, Guan-Sheng; Wang, Yu; Gao, Wen; Huang, Ying; Li, Cheng

    2005-04-14

    To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F = 4.14-105.36, Pscabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation-induced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. 32P colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3

  15. The Vulnerability of Vessels Involved in the Role of Embolism and Hypoperfusion in the Mechanisms of Ischemic Cerebrovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yong Peng Yu

    2016-01-01

    Full Text Available Accurate definition and better understanding of the mechanisms of stroke are crucial as this will guide the effective care and therapy. In this paper, we review the previous basic and clinical researches on the causes or mechanisms of ischemic cerebrovascular diseases (ICVD and interpret the correlation between embolism and hypoperfusion based on vascular stenosis and arterial intimal lesions. It was suggested that if there is no embolus (dynamic or in situ emboli, there might be no cerebral infarction. Three kinds of different clinical outcomes of TIA were theoretically interpreted based on its mechanisms. We suppose that there is a correlation between embolism and hypoperfusion, and which mechanisms (hypoperfusion or hypoperfusion induced microemboli playing the dominant role in each type of ICVD depends on the unique background of arterial intimal lesions (the vulnerability of vessels. That is to say, the vulnerability of vessels is involved in the role of embolism and hypoperfusion in the mechanisms of ischemic cerebrovascular diseases. This inference might enrich and provide better understandings for the underlying etiologies of ischemic cerebrovascular events.

  16. Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

    Science.gov (United States)

    Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

    2008-02-01

    We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

  17. Evolutionary molecular medicine.

    Science.gov (United States)

    Nesse, Randolph M; Ganten, Detlev; Gregory, T Ryan; Omenn, Gilbert S

    2012-05-01

    Evolution has long provided a foundation for population genetics, but some major advances in evolutionary biology from the twentieth century that provide foundations for evolutionary medicine are only now being applied in molecular medicine. They include the need for both proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, competition between alleles, co-evolution, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are transforming evolutionary biology in ways that create even more opportunities for progress at its interfaces with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and related principles to speed the development of evolutionary molecular medicine.

  18. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

    DEFF Research Database (Denmark)

    Leucci, E; Cocco, M; Onnis, A

    2008-01-01

    at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

  19. Study of the Chemical Mechanism Involved in the Formation of Tungstite in Benzyl Alcohol by the Advanced QEXAFS Technique

    DEFF Research Database (Denmark)

    Olliges‐Stadler, Inga; Stötzel, Jan; Koziej, Dorota

    2012-01-01

    Insight into the complex chemical mechanism for the formation of tungstite nanoparticles obtained by the reaction of tungsten hexachloride with benzyl alcohol is presented herein. The organic and inorganic species involved in the formation of the nanoparticles were studied by time‐dependent gas......‐scanning extended X‐ray absorption fine structure spectroscopy enabled the time‐dependent evolution of the starting compound, the intermediates and the product to be monitored over the full reaction period. The reaction starts with fast chlorine substitution and partial reduction during the dissolution...

  20. The progestin etonogestrel enhances the respiratory response to metabolic acidosis in newborn rats. Evidence for a mechanism involving supramedullary structures.

    Science.gov (United States)

    Loiseau, Camille; Osinski, Diane; Joubert, Fanny; Straus, Christian; Similowski, Thomas; Bodineau, Laurence

    2014-05-01

    Central congenital hypoventilation syndrome is a neuro-respiratory disease characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+) chemosensitivity has been observed in some central congenital hypoventilation syndrome patients coincidental with contraceptive treatment by a potent progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin effect remain unknown, although structures of medulla oblongata, midbrain or diencephalon are known to be targets for progesterone. In the present study, on ex vivo preparations of central nervous system of newborn rats, we show that acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the increased respiratory frequency induced by metabolic acidosis via a mechanism involving supramedullary structures located in pontine, mesencephalic or diencephalic regions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. General mechanism involved in subwavelength optics of conducting microstructures: charge-oscillation-induced light emission and interference.

    Science.gov (United States)

    Huang, Xian-Rong; Peng, Ru-Wen

    2010-04-01

    Interactions between light and conducting microstructures or nanostructures can result in a variety of novel phenomena, but their underlying mechanisms have not been completely understood. From calculations of surface charge density waves on conducting gratings and by comparing them with classical surface plasmons, we revealed a general yet concrete picture regarding the coupling of light to free electron oscillation on structured conducting surfaces that can lead to oscillating subwavelength charge patterns (i.e., structured surface plasmons). New wavelets emitted from these light sources then destructively interfere to form evanescent waves. This principle, usually combined with other mechanisms, is mainly a geometrical effect that can be universally involved in light scattering from all periodic and non-periodic structures containing free electrons. This picture may provide clear guidelines for developing conductor-based nano-optical devices.

  2. Meiotic restitution mechanisms involved in the formation of 2n pollen in Agave tequilana Weber and Agave angustifolia Haw.

    Science.gov (United States)

    Gómez-Rodríguez, Víctor Manuel; Rodríguez-Garay, Benjamín; Barba-Gonzalez, Rodrigo

    2012-01-01

    A cytological analysis of the microsporogenesis was carried out in the Agave tequilana and A. angustifolia species. Several abnormalities such as chromosomal bridges, lagging chromosomes, micronuclei, monads, dyads and triads were found. The morphological analysis of the pollen, together with the above-mentioned 2n microspores, allowed us to confirm the presence of 2n pollen as well as its frequency. In both A. tequilana and A. angustifolia two different mechanisms were observed: the first mechanism, a failure in the cytokinesis in meiosis II caused the formation of dyads with two 2n cells and triads containing two n cells and one 2n cell; the second mechanism, involves an abnormal spindle, which caused the formation of triads with two n cells and one 2n cell. Likewise, the presence of monads was detected in both species, these, might be caused by a failure of the cytokinesis in both meiotic divisions. This is the first report about the presence of a Second Division Restitution mechanism (SDR) which causes the formation of 2n pollen in the genus Agave. The genetic implications of the presence of 2n pollen in the genus Agave are discussed.

  3. Arbuscular mycorrhizal fungi for the biocontrol of plant-parasitic nematodes: a review of the mechanisms involved

    Directory of Open Access Journals (Sweden)

    Nele eSchouteden

    2015-11-01

    Full Text Available Arbuscular mycorrhizal fungi (AMF are obligate root symbionts that can protect their host plant against biotic stress factors such as plant parasitic nematode (PPN infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead towards future field applications of AMF against PPN. The scientific community has entered an exciting era that provide the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

  4. Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved.

    Science.gov (United States)

    Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

  5. Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved

    Science.gov (United States)

    Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M.

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead. PMID:26635750

  6. Evolutionary principles and their practical application.

    Science.gov (United States)

    Hendry, Andrew P; Kinnison, Michael T; Heino, Mikko; Day, Troy; Smith, Thomas B; Fitt, Gary; Bergstrom, Carl T; Oakeshott, John; Jørgensen, Peter S; Zalucki, Myron P; Gilchrist, George; Southerton, Simon; Sih, Andrew; Strauss, Sharon; Denison, Robert F; Carroll, Scott P

    2011-03-01

    Evolutionary principles are now routinely incorporated into medicine and agriculture. Examples include the design of treatments that slow the evolution of resistance by weeds, pests, and pathogens, and the design of breeding programs that maximize crop yield or quality. Evolutionary principles are also increasingly incorporated into conservation biology, natural resource management, and environmental science. Examples include the protection of small and isolated populations from inbreeding depression, the identification of key traits involved in adaptation to climate change, the design of harvesting regimes that minimize unwanted life-history evolution, and the setting of conservation priorities based on populations, species, or communities that harbor the greatest evolutionary diversity and potential. The adoption of evolutionary principles has proceeded somewhat independently in these different fields, even though the underlying fundamental concepts are the same. We explore these fundamental concepts under four main themes: variation, selection, connectivity, and eco-evolutionary dynamics. Within each theme, we present several key evolutionary principles and illustrate their use in addressing applied problems. We hope that the resulting primer of evolutionary concepts and their practical utility helps to advance a unified multidisciplinary field of applied evolutionary biology.

  7. Research traditions and evolutionary explanations in medicine.

    Science.gov (United States)

    Méthot, Pierre-Olivier

    2011-02-01

    In this article, I argue that distinguishing 'evolutionary' from 'Darwinian' medicine will help us assess the variety of roles that evolutionary explanations can play in a number of medical contexts. Because the boundaries of evolutionary and Darwinian medicine overlap to some extent, however, they are best described as distinct 'research traditions' rather than as competing paradigms. But while evolutionary medicine does not stand out as a new scientific field of its own, Darwinian medicine is united by a number of distinctive theoretical and methodological claims. For example, evolutionary medicine and Darwinian medicine can be distinguished with respect to the styles of evolutionary explanations they employ. While the former primarily involves 'forward looking' explanations, the latter depends mostly on 'backward looking' explanations. A forward looking explanation tries to predict the effects of ongoing evolutionary processes on human health and disease in contemporary environments (e.g., hospitals). In contrast, a backward looking explanation typically applies evolutionary principles from the vantage point of humans' distant biological past in order to assess present states of health and disease. Both approaches, however, are concerned with the prevention and control of human diseases. In conclusion, I raise some concerns about the claim that 'nothing in medicine makes sense except in the light of evolution'.

  8. Cognition and Culture in Evolutionary Context.

    Science.gov (United States)

    Colmenares, Fernando; Hernández-Lloreda, María Victoria

    2017-01-09

    In humans and other animals, the individuals' ability to adapt efficiently and effectively to the niches they have actively contributed to construct relies heavily on an evolved psychology which has been shaped by biological, social, and cultural processes over evolutionary time. As expected, although many of the behavioral and cognitive components of this evolved psychology are widely shared across species, many others are species-unique. Although many animal species are known to acquire group-specific traditions (or cultures) via social learning, human culture is unique in terms of its contents and characteristics (observable and unobservable products, cumulative effects, norm conformity, and norm enforcement) and of its cognitive underpinnings (imitation, instructed teaching, and language). Here we provide a brief overview of some of the issues that are currently tackled in the field. We also highlight some of the strengths of a biological, comparative, non-anthropocentric and evolutionarily grounded approach to the study of culture. The main contributions of this approach to the science of culture are its emphasis (a) on the integration of information on mechanisms, function, and evolution, and on mechanistic factors located at different levels of the biological hierarchy, and (b) on the search for general principles that account for commonalities and differences between species, both in the cultural products and in the processes of innovation, dissemination, and accumulation involved that operate during developmental and evolutionary timespans.

  9. Chemotherapeutics-resistance "arms" race: An update on mechanisms involved in resistance limiting EGFR inhibitors in lung cancer.

    Science.gov (United States)

    Singh, Pankaj Kumar; Silakari, Om

    2017-10-01

    Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc., in the development of tolerance towards the EGFR TKI's, along with other commonly known mechanisms, such as amplification of signalling pathways such as, c-MET, Erbb2, AXL, additional acquired secondary mutations (PIK3CA, BRAF), or phenotypic transformation (small cell or epithelial to mesenchymal transitions). Interestingly, a recent study showed development of resistance via another point mutation, C797S, in case of tumors which were previously resistant and were administered agents capable of overcoming T790M gatekeeper mutation based resistance. Thus, raising serious concern over the direction of drug development involving tyrosine kinases such as EGFR. Current approaches focussing on development of third generation inhibitors, dual inhibitors or inhibitors of HSP90 have shown significant activity but do not answer the long term question of resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  11. Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

    Science.gov (United States)

    Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

    2012-12-01

    The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

  12. Variants of Evolutionary Algorithms for Real-World Applications

    CERN Document Server

    Weise, Thomas; Michalewicz, Zbigniew

    2012-01-01

    Evolutionary Algorithms (EAs) are population-based, stochastic search algorithms that mimic natural evolution. Due to their ability to find excellent solutions for conventionally hard and dynamic problems within acceptable time, EAs have attracted interest from many researchers and practitioners in recent years. This book “Variants of Evolutionary Algorithms for Real-World Applications” aims to promote the practitioner’s view on EAs by providing a comprehensive discussion of how EAs can be adapted to the requirements of various applications in the real-world domains. It comprises 14 chapters, including an introductory chapter re-visiting the fundamental question of what an EA is and other chapters addressing a range of real-world problems such as production process planning, inventory system and supply chain network optimisation, task-based jobs assignment, planning for CNC-based work piece construction, mechanical/ship design tasks that involve runtime-intense simulations, data mining for the predictio...

  13. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    Science.gov (United States)

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

    Science.gov (United States)

    MURATA, Kozue; TOMOSADA, Yohsuke; VILLENA, Julio; CHIBA, Eriko; SHIMAZU, Tomoyuki; ASO, Hisashi; IWABUCHI, Noriyuki; XIAO, Jin-zhong; SAITO, Tadao; KITAZAWA, Haruki

    2014-01-01

    Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117. PMID:24936377

  15. Effect of food azo dye tartrazine on learning and memory functions in mice and rats, and the possible mechanisms involved.

    Science.gov (United States)

    Gao, Yonglin; Li, Chunmei; Shen, Jingyu; Yin, Huaxian; An, Xiulin; Jin, Haizhu

    2011-08-01

    Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. Animals were administered different doses of tartrazine for a period of 30 d and were evaluated by open-field test, step-through test, and Morris water maze test, respectively. Furthermore, the biomarkers of the oxidative stress and pathohistology were also measured to explore the possible mechanisms involved. The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test and decreased the retention latency in step-through tests. The decline in the activities of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats, and these changes were associated with the brain from oxidative damage. The dose levels of tartrazine in the present study produced a few adverse effects in learning and memory functions in animals. The mechanisms might be attributed to promoting lipid peroxidation products and reactive oxygen species, inhibiting endogenous antioxidant defense enzymes and the brain tissue damage. Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the Joint FAO/WHO Expert Committee on Food Additives in 1964, many new studies have been conducted. However, there is a little information about the effects on learning and memory performance. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in animals and its possible mechanism involved. Based on our results, we believe that more extensive assessment of food additives in current use is warranted. © 2011 Institute of Food

  16. Incorporating Development Into Evolutionary Psychology

    Directory of Open Access Journals (Sweden)

    David F. Bjorklund

    2016-09-01

    Full Text Available Developmental thinking is gradually becoming integrated within mainstream evolutionary psychology. This is most apparent with respect to the role of parenting, with proponents of life history theory arguing that cognitive and behavioral plasticity early in life permits children to select different life history strategies, with such strategies being adaptive solutions to different fitness trade-offs. I argue that adaptations develop and are based on the highly plastic nature of infants’ and children’s behavior/cognition/brains. The concept of evolved probabilistic cognitive mechanisms is introduced, defined as information processing mechanisms evolved to solve recurrent problems faced by ancestral populations that are expressed in a probabilistic fashion in each individual in a generation and are based on the continuous and bidirectional interaction over time at all levels of organization, from the genetic through the cultural. Early perceptual/cognitive biases result in behavior that, when occurring in a species-typical environment, produce continuous adaptive changes in behavior (and cognition, yielding adaptive outcomes. Examples from social learning and tool use are provided, illustrating the development of adaptations via evolved probabilistic cognitive mechanisms. The integration of developmental concepts into mainstream evolutionary psychology (and evolutionary concepts into mainstream developmental psychology will provide a clearer picture of what it means to be human.

  17. Insertion of molecular oxygen into a palladium(II) methyl bond: a radical chain mechanism involving palladium(III) intermediates.

    Science.gov (United States)

    Boisvert, Luc; Denney, Melanie C; Hanson, Susan Kloek; Goldberg, Karen I

    2009-11-04

    The reaction of (bipy)PdMe(2) (1) (bipy = 2,2'-bipyridine) with molecular oxygen results in the formation of the palladium(II) methylperoxide complex (bipy)PdMe(OOMe) (2). The identity of the product 2 has been confirmed by independent synthesis. Results of kinetic studies of this unprecedented oxygen insertion reaction into a palladium alkyl bond support the involvement of a radical chain mechanism. Reproducible rates, attained in the presence of the radical initiator 2,2'-azobis(2-methylpropionitrile) (AIBN), reveal that the reaction is overall first-order (one-half-order in both [1] and [AIBN], and zero-order in [O(2)]). The unusual rate law (half-order in [1]) implies that the reaction proceeds by a mechanism that differs significantly from those for organic autoxidations and for the recently reported examples of insertion of O(2) into Pd(II) hydride bonds. The mechanism for the autoxidation of 1 is more closely related to that found for the autoxidation of main group and early transition metal alkyl complexes. Notably, the chain propagation is proposed to proceed via a stepwise associative homolytic substitution at the Pd center of 1 with formation of a pentacoordinate Pd(III) intermediate.

  18. Metal and metalloid foliar uptake by various plant species exposed to atmospheric industrial fallout: Mechanisms involved for lead

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, E., E-mail: eva.schreck@ensat.fr [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); Foucault, Y. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); STCM, Societe de Traitements Chimiques des Metaux, 30 Avenue de Fondeyre 31200 Toulouse (France); Sarret, G. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Sobanska, S. [LASIR (UMR CNRS 8516), Universite de Lille 1, Bat. C5, 59655 Villeneuve d' Ascq cedex (France); Cecillon, L. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Castrec-Rouelle, M. [Universite Pierre and Marie Curie (UPMC-Paris 6), Bioemco (Biogeochimie et Ecologie des Milieux Continentaux), Site Jussieu, Tour 56, 4 Place Jussieu, 75252 Paris cedex 05 (France); Uzu, G. [Laboratoire d' Aerologie (UMR 5560), OMP, UPS 14, Avenue Edouard Belin, 31400 Toulouse (France); GET (UMR 5563), IRD, 14, Avenue Edouard Belin, 31400 Toulouse (France); Dumat, C. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France)

    2012-06-15

    Fine and ultrafine metallic particulate matters (PMs) are emitted from metallurgic activities in peri-urban zones into the atmosphere and can be deposited in terrestrial ecosystems. The foliar transfer of metals and metalloids and their fate in plant leaves remain unclear, although this way of penetration may be a major contributor to the transfer of metals into plants. This study focused on the foliar uptake of various metals and metalloids from enriched PM (Cu, Zn, Cd, Sn, Sb, As, and especially lead (Pb)) resulting from the emissions of a battery-recycling factory. Metal and metalloid foliar uptake by various vegetable species, exhibiting different morphologies, use (food or fodder) and life-cycle (lettuce, parsley and rye-grass) were studied. The mechanisms involved in foliar metal transfer from atmospheric particulate matter fallout, using lead (Pb) as a model element was also investigated. Several complementary techniques (micro-X-ray fluorescence, scanning electron microscopy coupled with energy dispersive X-ray microanalysis and time-of-flight secondary ion mass spectrometry) were used to investigate the localization and the speciation of lead in their edible parts, i.e. leaves. The results showed lead-enriched PM on the surface of plant leaves. Biogeochemical transformations occurred on the leaf surfaces with the formation of lead secondary species (PbCO{sub 3} and organic Pb). Some compounds were internalized in their primary form (PbSO{sub 4}) underneath an organic layer. Internalization through the cuticle or penetration through stomata openings are proposed as two major mechanisms involved in foliar uptake of particulate matter. - Graphical abstract: Overall picture of performed observations and mechanisms potentially involved in lead foliar uptake. Highlights: Black-Right-Pointing-Pointer Foliar uptake of metallic particulate matter (PM) is of environmental and health concerns. Black-Right-Pointing-Pointer The leaf morphology influences the adsorption

  19. Gouty involvement of the patella and extensor mechanism of the knee mimicking aggressive neoplasm. A case series.

    Science.gov (United States)

    Kester, Christopher; Wallace, Matthew T; Jelinek, James; Aboulafia, Albert

    2018-06-01

    Gout is a common inflammatory crystal deposition disease that occurs in many joints throughout the body. Active gout is most often associated with painful synovitis causing searing joint pains, but gout can also produce large masses of space-occupying deposits called tophi. Tophi are most frequently seen in juxta-articular locations with or without bony erosion and are often misdiagnosed as degenerative joint disease. Soft tissue deposits and tendon involvement are also known manifestations of gout, but can present with indeterminate and alarming findings on imaging. We present three cases of tophaceous gout mimicking aggressive neoplasms in the extensor mechanism of the knee. All cases presented as extensor tendon masses eroding into the patella, with imaging findings initially concerning for primary musculoskeletal malignancy.

  20. Wallerian degeneration slow mouse neurons are protected against cell death caused by mechanisms involving mitochondrial electron transport dysfunction.

    Science.gov (United States)

    Tokunaga, Shinji; Araki, Toshiyuki

    2012-03-01

    Ischemia elicits a variety of stress responses in neuronal cells, which result in cell death. wld(S) Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wld(S) mice are protected from, we exposed primary cultured neurons derived from wld(S) mice to various components of hypoxic stress. We found that wld(S) mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wld(S) mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that Wld(S) protein expression may provide protection against neuronal cell death caused by mechanisms involving mitochondrial electron transport dysfunction. Copyright © 2011 Wiley Periodicals, Inc.

  1. Involvement of Mζ-Like Protein Kinase in the Mechanisms of Conditioned Food Aversion Memory Reconsolidation in the Helix lucorum.

    Science.gov (United States)

    Solntseva, S V; Kozyrev, S A; Nikitin, V P

    2015-06-01

    We studied the involvement of Mζ-like protein kinase (PKMζ) into mechanisms of conditioned food aversion memory reconsolidation in Helix lucorum. Injections PKMζ inhibitor ZIP in a dose of 5 mg/kg on day 2 or 10 after learning led to memory impairment and amnesia development. Injections of the inhibitor in doses of 1.5 or 2.5 mg/kg had no effect. Repeated training on day 11 after induction of amnesia resulted in the formation of memory on the same type of food aversion similar to first training. The number of combinations of conditional (food) and reinforcing (electrical shock) stimuli was similar during initial and repeated training. We hypothesize that the inhibition of Mζ-like protein kinase erases the memory trace and a new memory is formed during repeated training.

  2. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment.

    Science.gov (United States)

    Zuo, Li; Tozawa, Keiichi; Okada, Atsushi; Yasui, Takahiro; Taguchi, Kazumi; Ito, Yasuhiko; Hirose, Yasuhiko; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Ando, Ryosuke; Itoh, Yasunori; Zou, Jiangang; Kohri, Kenjiro

    2014-06-01

    We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation. Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells. Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Attractive evolutionary equilibria

    OpenAIRE

    Roorda, Berend; Joosten, Reinoud

    2011-01-01

    We present attractiveness, a refinement criterion for evolutionary equilibria. Equilibria surviving this criterion are robust to small perturbations of the underlying payoff system or the dynamics at hand. Furthermore, certain attractive equilibria are equivalent to others for certain evolutionary dynamics. For instance, each attractive evolutionarily stable strategy is an attractive evolutionarily stable equilibrium for certain barycentric ray-projection dynamics, and vice versa.

  4. Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

    Energy Technology Data Exchange (ETDEWEB)

    López-Canales, J.S. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico); Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); Lozano-Cuenca, J.; Muãoz-Islas, E.; Aguilar-Carrasco, J.C. [Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); López-Canales, O.A.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; Valencia-Hernández, I.; Castillo-Henkel, C. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico)

    2015-03-27

    Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca{sup 2+}-activated K{sup +} channels were involved in this effect.

  5. Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

    Directory of Open Access Journals (Sweden)

    Valérie Wolff

    2015-01-01

    Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

  6. GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

    Science.gov (United States)

    Stepanović-Petrović, Radica M; Tomić, Maja A; Vucković, Sonja M; Kocev, Nikola; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

    2008-01-01

    The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation. Copyright 2008 S. Karger AG, Basel.

  7. Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

    International Nuclear Information System (INIS)

    Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

    2013-01-01

    The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

  8. Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

    International Nuclear Information System (INIS)

    López-Canales, J.S.; Lozano-Cuenca, J.; Muãoz-Islas, E.; Aguilar-Carrasco, J.C.; López-Canales, O.A.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; Valencia-Hernández, I.; Castillo-Henkel, C.

    2015-01-01

    Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca 2+ -activated K + channels were involved in this effect

  9. Mecanismos envolvidos na cicatrização: uma revisão Mechanisms involved in wound healing: a revision

    Directory of Open Access Journals (Sweden)

    Carlos Aberto Balbino

    2005-03-01

    Full Text Available Os mecanismos envolvidos no processo de reparo de tecidos estão revisados nesse trabalho. O processo de cicatrização ocorre fundamentalmente em três fases: inflamação, formação de tecido de granulação e deposição de matriz extracelular e remodelação. Os eventos celulares e tissulares de cada uma dessas fases estão descritos e discutidos. Os mediadores químicos estão correlacionados com os eventos do processo de cicatrização e as células envolvidas. Especial ênfase é dada à participação dos fatores de crescimento.The mechanisms involved in tissue repair are revised. The wound healing process occurs basically in three phases: inflammation, formation of granulating tissue and extracellular tissue deposition, and tissue remodeling. The cellular and tissue events of each phase are described and discussed. The chemical mediators and their interplay with the wound healing events and cells involved are also discussed. However, especial attention was given to the role played by the growth factors in the tissue repair process.

  10. Gastroprotective and ulcer healing effects of hydroethanolic extract of leaves of Caryocar coriaceum: Mechanisms involved in the gastroprotective activity.

    Science.gov (United States)

    de Lacerda Neto, Luis Jardelino; Ramos, Andreza Guedes Barbosa; Santos Sales, Valterlucio; de Souza, Severino Denicio Gonçalves; Dos Santos, Antonia Thassya Lucas; de Oliveira, Larissa Rolim; Kerntopf, Marta Regina; de Albuquerque, Thais Rodrigues; Coutinho, Henrique Douglas Melo; Quintans-Júnior, Lucindo Jose; Wanderley, Almir Gonçalves; de Menezes, Irwin Rose Alencar

    2017-01-05

    This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α 2 -adrenergic receptors and primary afferent neurons sensitive to capsaicin were involved in the mechanism of gastric protection, in addition to the contribution of NO and prostaglandins. The results show that extract is a promising candidate for the treatment of gastric ulcers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Polymorphic Evolutionary Games.

    Science.gov (United States)

    Fishman, Michael A

    2016-06-07

    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Mechanisms involved in repairing the lesions induced in pBR 322 by PUVA treatment (8-Methoxypsoralen + ultraviolet A light)

    International Nuclear Information System (INIS)

    Bauluz, C.

    1988-01-01

    This work deals with the genotoxic effects derived from damaging pBR322 DNA through PUVA treatment (8-Methoxypsoralen plusUVA light), both with respect to the lethality and mutagenicity of the lesions produced by the treatment. The mechanisms involved in the repair of the plasmid lesions have been investigated by transforming several strains of E. coli differing in their DNA-repair capacities. The frequency, distribution and type of mutations occurring in a restriction fragment of the damaged plasmid were determined in order to establish the mutagenic features of the PUVA treatment. Damages produced bY PUVA habe a strong lethal effect on plasmid survival; however, partial recovery is possible through some of the bacterial DNA repair pathways, namely Excision repair, SOS-repair and a third mechanism which appears to be independent from the analised genes and is detected at high density of lesions per plasmid molecule. PUVA treatment produces a high increase in plasmid mutagenesis; however, the contribution of such an increase to the whole plasmid survival is negligible. Only punctual mutations were detected and consisted mainly in base-pair substitutions. Some mutation-prone regions were sound inside the investigated DNA fragment, a though their existence is more likely to be related with the structure acquired by the damaged DNA than with the type of damaging agent. (Author)

  13. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs).

    Science.gov (United States)

    Wang, Huizheng; Zhang, Kai; Zhu, Jie; Song, Weiwei; Zhao, Li; Zhang, Xiuguo

    2013-01-01

    Polyhydroxyalkanoates (PHAs) have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC), which belongs to (R)-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R)-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R)-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. The data in our study reveal the regulatory mechanism of an (R)-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  14. Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

    Science.gov (United States)

    Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

    2016-08-01

    During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Effects and mechanisms of 3α,5α,-THP on emotion, motivation, and reward functions involving pregnane xenobiotic receptor

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2012-01-01

    Full Text Available Progestogens [progesterone (P4 and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P4 metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP, influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA, 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P4, in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence. Thus, further understanding of 3α,5α-THP’s role and mechanisms to enhance affective and motivated

  16. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

    Directory of Open Access Journals (Sweden)

    Huizheng Wang

    Full Text Available Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic.We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC.The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  17. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

    International Nuclear Information System (INIS)

    Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

    2014-01-01

    Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

  18. Evolutionary algorithms for mobile ad hoc networks

    CERN Document Server

    Dorronsoro, Bernabé; Danoy, Grégoire; Pigné, Yoann; Bouvry, Pascal

    2014-01-01

    Describes how evolutionary algorithms (EAs) can be used to identify, model, and minimize day-to-day problems that arise for researchers in optimization and mobile networking. Mobile ad hoc networks (MANETs), vehicular networks (VANETs), sensor networks (SNs), and hybrid networks—each of these require a designer’s keen sense and knowledge of evolutionary algorithms in order to help with the common issues that plague professionals involved in optimization and mobile networking. This book introduces readers to both mobile ad hoc networks and evolutionary algorithms, presenting basic concepts as well as detailed descriptions of each. It demonstrates how metaheuristics and evolutionary algorithms (EAs) can be used to help provide low-cost operations in the optimization process—allowing designers to put some “intelligence” or sophistication into the design. It also offers efficient and accurate information on dissemination algorithms topology management, and mobility models to address challenges in the ...

  19. Evolutionary principles and their practical application

    DEFF Research Database (Denmark)

    Hendry, A. P.; Kinnison, M. T.; Heino, M.

    2011-01-01

    Evolutionary principles are now routinely incorporated into medicine and agriculture. Examples include the design of treatments that slow the evolution of resistance by weeds, pests, and pathogens, and the design of breeding programs that maximize crop yield or quality. Evolutionary principles...... are also increasingly incorporated into conservation biology, natural resource management, and environmental science. Examples include the protection of small and isolated populations from inbreeding depression, the identification of key traits involved in adaptation to climate change, the design...... of harvesting regimes that minimize unwanted life-history evolution, and the setting of conservation priorities based on populations, species, or communities that harbor the greatest evolutionary diversity and potential. The adoption of evolutionary principles has proceeded somewhat independently...

  20. Mechanisms Involved in Acquisition of blaNDM Genes by IncA/C2 and IncFIIY Plasmids.

    Science.gov (United States)

    Wailan, Alexander M; Sidjabat, Hanna E; Yam, Wan Keat; Alikhan, Nabil-Fareed; Petty, Nicola K; Sartor, Anna L; Williamson, Deborah A; Forde, Brian M; Schembri, Mark A; Beatson, Scott A; Paterson, David L; Walsh, Timothy R; Partridge, Sally R

    2016-07-01

    blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection.

    Science.gov (United States)

    Lamont, Kim T; Somers, Sarin; Lacerda, Lydia; Opie, Lionel H; Lecour, Sandrine

    2011-05-01

    Epidemiological studies suggest that regular moderate consumption of red wine confers cardioprotection but the mechanisms involved in this effect remain unclear. Recent studies demonstrate the presence of melatonin in wine. We propose that melatonin, at a concentration found in red wine, confers cardioprotection against ischemia-reperfusion injury. Furthermore, we investigated whether both melatonin and resveratrol protect via the activation of the newly discovered survivor activating factor enhancement (SAFE) prosurvival signaling pathway that involves the activation of tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Isolated perfused male mouse (wild type, TNFα receptor 2 knockout mice, and cardiomyocyte-specific STAT3-deficient mice) or rat hearts (Wistars) were subjected to ischemia-reperfusion. Resveratrol (2.3 mg/L) or melatonin (75 ng/L) was perfused for 15 min with a 10-min washout period prior to an ischemia-reperfusion insult. Infarct size was measured at the end of the protocol, and Western blot analysis was performed to evaluate STAT3 activation prior to the ischemic insult. Both resveratrol and melatonin, at concentrations found in red wine, significantly reduced infarct size compared with control hearts in wild-type mouse hearts (25 ± 3% and 25 ± 3% respectively versus control 69 ± 3%, P < 0.001) but failed to protect in TNF receptor 2 knockout or STAT3-deficient mice. Furthermore, perfusion with either melatonin or resveratrol increased STAT3 phosphorylation prior to ischemia by 79% and 50%, respectively (P < 0.001 versus control). Our data demonstrate that both melatonin and resveratrol, as found in red wine, protect the heart in an experimental model of myocardial infarction via the SAFE pathway. © 2011 John Wiley & Sons A/S.

  2. Testing evolutionary convergence on Europa

    Energy Technology Data Exchange (ETDEWEB)

    Chela-Flores, Julian [Instituto de Estudios Avanzados, Caracas (Venezuela); [Abdus Salam International Centre for Theoretical Physics, Trieste (Italy)

    2002-11-01

    A major objective in solar system exploration is the insertion of appropriate biology-oriented experiments in future missions. We discuss various reasons for suggesting that this type of research be considered a high priority for feasibility studies and, subsequently, for technological development of appropriate melters and submersibles. Based on numerous examples, we argue in favour of the assumption that Darwin's theory is valid for the evolution of life anywhere in the universe. We have suggested how to obtain preliminary insights into the question of the distribution of life in the universe. Universal evolution of intelligent behaviour is at the end of an evolutionary pathway, in which evolution of ion channels in the membrane of microorganisms occurs in its early stages. Further, we have argued that a preliminary test of this conjecture is feasible with experiments on the Europan surface or ocean, involving evolutionary biosignatures (ion channels). This aspect of the exploration for life in the solar system should be viewed as a complement to the astronomical approach for the search of evidence of the later stages of the evolutionary pathways towards intelligent behaviour. (author)

  3. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    Energy Technology Data Exchange (ETDEWEB)

    Ouadah-Boussouf, Nafia; Babin, Patrick J., E-mail: p.babin@gpp.u-bordeaux1.fr

    2016-03-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  4. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    International Nuclear Information System (INIS)

    Ouadah-Boussouf, Nafia; Babin, Patrick J.

    2016-01-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  5. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action.

    Directory of Open Access Journals (Sweden)

    Fernanda Fonseca-Silva

    2016-02-01

    Full Text Available The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis.Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers.In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports

  6. Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5’UTR and PI3K Signaling

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2018-06-01

    Full Text Available The α-secretase “a disintegrin and metalloproteinase domain-containing protein” (ADAM10 is involved in the processing of amyloid precursor protein (APP. Upregulation of ADAM10 precludes the generation of neurotoxic β-amyloid protein (Aβ and represents a plausible therapeutic strategy for Alzheimer’s disease (AD. In this study, we explored compounds that can potentially promote the expression of ADAM10. Therefore, we performed high-throughput small-molecule screening in SH-SY5Y (human neuroblastoma cells that stably express a luciferase reporter gene driven by the ADAM10 promoter, including a portion of its 5’-untranslated region (5’UTR. This has led to the discovery of cosmosiin (apigenin 7-O-β-glucoside. Here, we report that in human cell lines (SH-SY5Y and HEK293, cosmosiin proportionally increased the levels of the immature and mature forms of the ADAM10 protein without altering its mRNA level. This effect was attenuated by translation inhibitors or by deleting the 5’UTR of ADAM10, suggesting that a translational mechanism was responsible for the increased levels of ADAM10. Luciferase deletion assays revealed that the first 144 nucleotides of the 5’UTR were necessary for mediating the cosmosiin-induced enhancement of ADAM10 expression in SH-SY5Y cells. Cosmosiin failed to increase the levels of the ADAM10 protein in murine cells, which lack native expression of the ADAM10 transcript containing the identified 5’UTR element. The potential signaling pathway may involve phosphatidylinositide 3-kinase (PI3K because pharmacological inhibition of PI3K attenuated the effect of cosmosiin on the expression of the ADAM10 protein. Finally, cosmosiin attenuated Aβ generation because the levels of Aβ40/42 in HEK-APP cells were significantly reduced after cosmosiin treatment. Collectively, we found that the first 144 nucleotides of the ADAM10 5’UTR, and PI3K signaling, are involved in cosmosiin-induced enhancement of the expression

  7. Human compulsivity: A perspective from evolutionary medicine.

    Science.gov (United States)

    Stein, Dan J; Hermesh, Haggai; Eilam, David; Segalas, Cosi; Zohar, Joseph; Menchon, Jose; Nesse, Randolph M

    2016-05-01

    Biological explanations address not only proximal mechanisms (for example, the underlying neurobiology of obsessive-compulsive disorder), but also distal mechanisms (that is, a consideration of how particular neurobiological mechanisms evolved). Evolutionary medicine has emphasized a series of explanations for vulnerability to disease, including constraints, mismatch, and tradeoffs. The current paper will consider compulsive symptoms in obsessive-compulsive and related disorders and behavioral addictions from this evolutionary perspective. It will argue that while obsessive-compulsive disorder (OCD) is typically best conceptualized as a dysfunction, it is theoretically and clinically valuable to understand some symptoms of obsessive-compulsive and related disorders in terms of useful defenses. The symptoms of behavioral addictions can also be conceptualized in evolutionary terms (for example, mismatch), which in turn provides a sound foundation for approaching assessment and intervention. Copyright © 2016. Published by Elsevier B.V.

  8. Understanding the mind from an evolutionary perspective: an overview of evolutionary psychology.

    Science.gov (United States)

    Shackelford, Todd K; Liddle, James R

    2014-05-01

    The theory of evolution by natural selection provides the only scientific explanation for the existence of complex adaptations. The design features of the brain, like any organ, are the result of selection pressures operating over deep time. Evolutionary psychology posits that the human brain comprises a multitude of evolved psychological mechanisms, adaptations to specific and recurrent problems of survival and reproduction faced over human evolutionary history. Although some mistakenly view evolutionary psychology as promoting genetic determinism, evolutionary psychologists appreciate and emphasize the interactions between genes and environments. This approach to psychology has led to a richer understanding of a variety of psychological phenomena, and has provided a powerful foundation for generating novel hypotheses. Critics argue that evolutionary psychologists resort to storytelling, but as with any branch of science, empirical testing is a vital component of the field, with hypotheses standing or falling with the weight of the evidence. Evolutionary psychology is uniquely suited to provide a unifying theoretical framework for the disparate subdisciplines of psychology. An evolutionary perspective has provided insights into several subdisciplines of psychology, while simultaneously demonstrating the arbitrary nature of dividing psychological science into such subdisciplines. Evolutionary psychologists have amassed a substantial empirical and theoretical literature, but as a relatively new approach to psychology, many questions remain, with several promising directions for future research. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. © 2014 John Wiley & Sons, Ltd.

  9. Evolutionary ecology of virus emergence.

    Science.gov (United States)

    Dennehy, John J

    2017-02-01

    The cross-species transmission of viruses into new host populations, termed virus emergence, is a significant issue in public health, agriculture, wildlife management, and related fields. Virus emergence requires overlap between host populations, alterations in virus genetics to permit infection of new hosts, and adaptation to novel hosts such that between-host transmission is sustainable, all of which are the purview of the fields of ecology and evolution. A firm understanding of the ecology of viruses and how they evolve is required for understanding how and why viruses emerge. In this paper, I address the evolutionary mechanisms of virus emergence and how they relate to virus ecology. I argue that, while virus acquisition of the ability to infect new hosts is not difficult, limited evolutionary trajectories to sustained virus between-host transmission and the combined effects of mutational meltdown, bottlenecking, demographic stochasticity, density dependence, and genetic erosion in ecological sinks limit most emergence events to dead-end spillover infections. Despite the relative rarity of pandemic emerging viruses, the potential of viruses to search evolutionary space and find means to spread epidemically and the consequences of pandemic viruses that do emerge necessitate sustained attention to virus research, surveillance, prophylaxis, and treatment. © 2016 New York Academy of Sciences.

  10. Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

    International Nuclear Information System (INIS)

    He Chengyong; Zuo Zhenghong; Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin; Wang Chonggang

    2011-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

  11. Electroencephalogram oscillations support the involvement of task-unrelated thoughts in the mechanism of boredom: A pilot study.

    Science.gov (United States)

    Miyauchi, Eri; Kawasaki, Masahiro

    2018-06-11

    Boredom is a universal experience; however, the neural mechanisms underlying the phenomenon remain unclear. Previous research suggests that boredom is related to attentional failure and derives a possible explanation for the cognitive processes of boredom as a product of appraisals made about task-unrelated thoughts. There are little published data regarding proposed processes from neuroscientific perspectives. Therefore, the authors aimed to examine whether cognitive processes of boredom with task-unrelated thoughts followed by appraisals of them can be explained by examining oscillatory correlates. Electroencephalography was used to measure changes in neural oscillatory activity during subjective experiences of boredom or dislike in healthy subjects. Using this approach, temporal information of brain activity particular to the boredom experience was acquired. Additionally, the Adult Attention-Deficit Hyperactivity Disorder Self-Report Scale was used to evaluate the effects of attentional deficits in the neural processing of boredom. Tonic increase in theta and transient increases in alpha activity were exhibited before the key press response for experiencing boredom; however, only tonic increases in theta amplitudes were boredom specific. The results of this pilot study suggest that the boredom experience is possibly associated with cognitive processes involved in task-unrelated thoughts, followed by their appraisals to be bored, mediated by alpha and theta activity. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin.

    Science.gov (United States)

    Ouadah-Boussouf, Nafia; Babin, Patrick J

    2016-03-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Involvement of oxidative stress in the mechanism of p,p'-DDT-induced nephrotoxicity in adult rats.

    Science.gov (United States)

    Marouani, Neila; Hallegue, Dorsaf; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais; Tebourbi, Olfa

    2017-07-01

    The 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDT) is an organochlorine pesticide that persists in the environment and has a risk to human health. We investigated whether p,p'-DDT-induces nephrotoxicity in rats and whether oxidative stress and apoptosis are involved in the pathogenesis of this process. Male rats received the pesticide at doses of 50 and 100 mg/kg for 10 days. Renal damage was evaluated by histopathological examination and serum markers. The oxidative stress was evaluated by lipid peroxidation (LPO), metallothioneins (MTs) and protein carbonyl levels. Antioxidant enzymes were assessed by determination of superoxide dismutase (SOD) and catalase (CAT) activities. Glutathione-dependent enzymes and reducing power in kidney were evaluated by glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities. Renal tubular cells apoptosis was assessed through the TUNEL assay. After 10 days of treatment, an increase of serum creatinine and urea levels occurred, LPO and protein carbonyl levels were increased, while MTs level, SOD and CAT activities were decreased. Besides, the GPx, GR, GST, and GSH activities were decreased. Histological alterations in kidney tissue and intense apoptosis in renal tubular cells were observed. These results suggest that DDT sub-acute treatment causes oxidative stress and apoptosis, which may be the chief mechanisms of DDT-induced nephrotoxicity.

  14. Immunological mechanisms involved in the protection against intestinal taeniosis elicited by oral immunization with Taenia solium calreticulin.

    Science.gov (United States)

    Leon-Cabrera, Sonia; Cruz-Rivera, Mayra; Mendlovic, Fela; Romero-Valdovinos, Mirza; Vaughan, Gilberto; Salazar, Ana María; Avila, Guillermina; Flisser, Ana

    2012-11-01

    Oral immunization with functional recombinant Taenia solium calreticulin (rTsCRT) induces 37% reduction in tapeworm burden in the experimental model of intestinal taeniosis in hamsters. Furthermore, tapeworms recovered from vaccinated animals exhibit diminished length, being frequently found in more posterior parts of the small intestine. The aim of this study was to analyze the immunological mechanisms involved in protection in response to rTsCRT oral immunization. Hamsters were orally immunized with rTsCRT using cholera toxin (CT) as adjuvant, weekly for 4 weeks. Fifteen days after the last boost animals were challenged with four T. solium cysticerci. Reduction in the adult worm recovery and increased transcription of mRNA for IL-4 and IFN-γ in the mucosa of rTsCRT+CT immunized animals were observed. Immunization also induced goblet cell hyperplasia in the mucosa surrounding the implantation site of the parasite. Specific IgG and IgA antibodies in serum and fecal supernatants were detected after the second immunization, being more pronounced after challenge. Our data suggest that oral vaccination with rTsCRT+CT regulates a local expression of IL-4 and IFN-γ, stimulating secretion of IgA that, together with the increase of goblet cells and mucin production, could result in an unfavorable environment for T. solium promoting an impaired tapeworm development. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Clinical trial involving sufferers and non-sufferers of cervicogenic headache (CGH): potential mechanisms of action of photobiomodulation (Conference Presentation)

    Science.gov (United States)

    Liebert, Ann D.; Bicknell, Brian

    2017-02-01

    Photobiomodulation (PBM) is an effective tool for the management of spinal pain including inflammation of facet joints. Apart from cervical and lumbar joint pain the upper cervical spine facet joint inflammation can result in the CGH (traumatic or atraumatic in origin). This condition affects children, adults and elders and is responsible for 19% of chronic headache and up to 33% of patients in pain clinics. The condition responds well to physiotherapy, facet joint injection, radiofrequency neurotomy and surgery at a rate of 75%. The other 25% being unresponsive to treatment with no identified features of unresponsiveness. In other conditions of chronic unresponsive cervical pain have responded to photobiomodulation at a level of 80% in the short and medium term. A clinical trial was therefore conducted on a cohort of atraumatic patients from the ages of 5-93 (predominantly Neurologist referred / familial sufferers 2/3 generations vertically and laterally) who had responded to a course of PBM and physiotherapy. The CGH sufferers and their non CGH suffering relatives over these generations were then compared for features that distinguish the two groups. Fifty parameters were tested (anthropmetric, movement and neural tension tests included) and there was a noted difference in tandem stance between the groups (.04 significance with repeated measures). As this impairment is common to benign ataxia and migrainous vertigo and in these conditions there is an ion channelopathy (especially potassium channelopathy). A postulated mechanism of action of PBM would involve modulation of ion channels and this is discussed in this presentation.

  16. Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction

    Science.gov (United States)

    Zhou, Shan-Shan; Xu, Jun; Zhu, He; Wu, Jie; Xu, Jin-Di; Yan, Ru; Li, Xiu-Yang; Liu, Huan-Huan; Duan, Su-Min; Wang, Zhuo; Chen, Hu-Biao; Shen, Hong; Li, Song-Lin

    2016-03-01

    Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care.

  17. Mechanisms involved in the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation in mice

    International Nuclear Information System (INIS)

    De Ruysscher, D; Waer, M.; Vandeputte, M.; Van der Schueren, E.

    1990-01-01

    The mechanisms involved in the differential recovery of CD4 (helper/inducer phenotype) and CD8 (Cytotoxic/suppressor phenotype) T-lymphocytes after fractionated local irradiation were investigated. In mice, a better recovery of CD4 cells than of CD8 cells was found, while the reverse has been described in humans. Differences in radiosensivitity between CD4 and CD8 mouse splenocytes could not be found. No sequestration of CD8 cells in irradiated tissues could be demonstrated. Irradiation of the thymus did not influence the observed immune changes. Altered thymic production of CD4 and CD8 cells could be excluded by intrathymic injection of FITC (fluorescein isothiocyanate). Hindlimb and tail irradiation did suggest that the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation is determined by extrathymic factors in man and mice, and that the observed differences in immune recovery between man and mice are due to defective thymic function in the former and normal function in the latter. (author). 12 refs.; 5 figs.; 2 tabs

  18. Mechanisms involved in the hydrothermal growth of ultra-thin and high aspect ratio ZnO nanowires

    Science.gov (United States)

    Demes, Thomas; Ternon, Céline; Morisot, Fanny; Riassetto, David; Legallais, Maxime; Roussel, Hervé; Langlet, Michel

    2017-07-01

    Hydrothermal synthesis of ZnO nanowires (NWs) with tailored dimensions, notably high aspect ratios (AR) and small diameters, is a major concern for a wide range of applications and still represents a challenging and recurring issue. In this work, an additive-free and reproducible hydrothermal procedure has been developed to grow ultra-thin and high AR ZnO NWs on sol-gel deposited ZnO seed layers. Controlling the substrate temperature and using a low reagent concentration (1 mM) has been found to be essential for obtaining such NWs. We show that the NW diameter remains constant at about 20-25 nm with growth time contrary to the NW length that can be selectively increased leading to NWs with ARs up to 400. On the basis of investigated experimental conditions along with thermodynamic and kinetic considerations, a ZnO NW growth mechanism has been developed which involves the formation and growth of nuclei followed by NW growth when the nuclei reach a critical size of about 20-25 nm. The low reagent concentration inhibits NW lateral growth leading to ultra-thin and high AR NWs. These NWs have been assembled into electrically conductive ZnO nanowire networks, which opens attractive perspectives toward the development of highly sensitive low-cost gas- or bio-sensors.

  19. Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

    Energy Technology Data Exchange (ETDEWEB)

    He Chengyong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Zuo Zhenghong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Wang Chonggang, E-mail: cgwang@xmu.edu.cn [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

    2011-01-25

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

  20. Origins of evolutionary transitions

    Indian Academy of Sciences (India)

    2014-03-15

    Mar 15, 2014 ... ... of events: 'Entities that were capable of independent replication ... There have been many major evolutionary events that this definition of .... selection at level x to exclusive selection at x – will probably require a multiplicity ...

  1. Evolutionary relationships among Astroviridae

    NARCIS (Netherlands)

    Lukashov, Vladimir V.; Goudsmit, Jaap

    2002-01-01

    To study the evolutionary relationships among astroviruses, all available sequences for members of the family Astroviridae were collected. Phylogenetic analysis distinguished two deep-rooted groups: one comprising mammalian astroviruses, with ovine astrovirus being an outlier, and the other

  2. Evolutionary Multiplayer Games

    OpenAIRE

    Gokhale, Chaitanya S.; Traulsen, Arne

    2014-01-01

    Evolutionary game theory has become one of the most diverse and far reaching theories in biology. Applications of this theory range from cell dynamics to social evolution. However, many applications make it clear that inherent non-linearities of natural systems need to be taken into account. One way of introducing such non-linearities into evolutionary games is by the inclusion of multiple players. An example is of social dilemmas, where group benefits could e.g.\\ increase less than linear wi...

  3. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    Science.gov (United States)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

  4. Metabotropic Glutamate Receptor 7 Modulates the Rewarding Effects of Cocaine in Rats: Involvement of a Ventral Pallidal GABAergic Mechanism

    Science.gov (United States)

    Li, Xia; Li, Jie; Peng, Xiao-Qing; Spiller, Krista; Gardner, Eliot L; Xi, Zheng-Xiong

    2013-01-01

    The metabotropic glutamate receptor 7 (mGluR7) has received much attention as a potential target for the treatment of epilepsy, major depression, and anxiety. In this study, we investigated the possible involvement of mGluR7 in cocaine reward in animal models of drug addiction. Pretreatment with the selective mGluR7 allosteric agonist N,N’-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082; 1-20 mg/kg, i.p.) dose-dependently inhibited cocaine-induced enhancement of electrical brain-stimulation reward and intravenous cocaine self-administration under both fixed-ratio and progressive-ratio reinforcement conditions, but failed to alter either basal or cocaine-enhanced locomotion or oral sucrose self-administration, suggesting a specific inhibition of cocaine reward. Microinjections of AMN082 (1–5 μg/μl per side) into the nucleus accumbens (NAc) or ventral pallidum (VP), but not dorsal striatum, also inhibited cocaine self-administration in a dose-dependent manner. Intra-NAc or intra-VP co-administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP, 5 μg/μl per side), a selective mGluR7 allosteric antagonist, significantly blocked AMN082’s action, suggesting an effect mediated by mGluR7 in these brain regions. In vivo microdialysis demonstrated that cocaine (10 mg/kg, i.p.) priming significantly elevated extracellular DA in the NAc or VP, while decreasing extracellular GABA in VP (but not in NAc). AMN082 pretreatment selectively blocked cocaine-induced changes in extracellular GABA, but not in DA, in both naive rats and cocaine self-administration rats. These data suggest: (1) mGluR7 is critically involved in cocaine’s acute reinforcement; (2) GABA-, but not DA-, dependent mechanisms in the ventral striatopallidal pathway appear to underlie AMN082’s actions; and (3) AMN082 or other mGluR7-selective agonists may be useful in the treatment of cocaine addiction. PMID:19158667

  5. The Evolutionary Puzzle of Suicide

    Directory of Open Access Journals (Sweden)

    Henri-Jean Aubin

    2013-12-01

    Full Text Available Mechanisms of self-destruction are difficult to reconcile with evolution’s first rule of thumb: survive and reproduce. However, evolutionary success ultimately depends on inclusive fitness. The altruistic suicide hypothesis posits that the presence of low reproductive potential and burdensomeness toward kin can increase the inclusive fitness payoff of self-removal. The bargaining hypothesis assumes that suicide attempts could function as an honest signal of need. The payoff may be positive if the suicidal person has a low reproductive potential. The parasite manipulation hypothesis is founded on the rodent—Toxoplasma gondii host-parasite model, in which the parasite induces a “suicidal” feline attraction that allows the parasite to complete its life cycle. Interestingly, latent infection by T. gondii has been shown to cause behavioral alterations in humans, including increased suicide attempts. Finally, we discuss how suicide risk factors can be understood as nonadaptive byproducts of evolved mechanisms that malfunction. Although most of the mechanisms proposed in this article are largely speculative, the hypotheses that we raise accept self-destructive behavior within the framework of evolutionary theory.

  6. On the evolutionary arms-race between Utetheisa ornatrix moth and its Florida host, Crotalaria pumila: chemical attraction, and mechanical defense

    Science.gov (United States)

    While Utetheisa ornatrix larvae are able to develop through feeding only on foliage of its hostplants in the genus Crotalaria, in later instars they are attracted to seeds as a richer source of alkaloids. Recently, it was demonstrated that seeds receive different degrees of mechanical protection fro...

  7. Evolutionary responses of native plant species to invasive plants: a review.

    Science.gov (United States)

    Oduor, Ayub M O

    2013-12-01

    Strong competition from invasive plant species often leads to declines in abundances and may, in certain cases, cause localized extinctions of native plant species. Nevertheless, studies have shown that certain populations of native plant species can co-exist with invasive plant species,suggesting the possibility of adaptive evolutionary responses of those populations to the invasive plants. Empirical inference of evolutionary responses of the native plant species to invasive plants has involved experiments comparing two conspecific groups of native plants for differences in expression of growth/reproductive traits: populations that have experienced competition from the invasive plant species (i.e. experienced natives) versus populations with no known history of interactions with the invasive plant species (i.e. naıve natives). Here, I employ a meta-analysis to obtain a general pattern of inferred evolutionary responses of native plant species from 53 such studies. In general, the experienced natives had significantly higher growth/reproductive performances than naıve natives, when grown with or without competition from invasive plants.While the current results indicate that certain populations of native plant species could potentially adapt evolutionarily to invasive plant species, the ecological and evolutionary mechanisms that probably underlie such evolutionary responses remain unexplored and should be the focus of future studies.

  8. Cytotoxic mechanisms of Zn2+ and Cd2+ involve Na+/H+ exchanger (NHE) activation by ROS

    International Nuclear Information System (INIS)

    Koutsogiannaki, Sophia; Evangelinos, Nikolaos; Koliakos, George; Kaloyianni, Martha

    2006-01-01

    The signaling mechanism induced by cadmium (Cd) and zinc (Zn) in gill cells of Mytilus galloprovincialis was investigated. Both metals cause an increase in ·O 2 - production, with Cd to be more potent (216 ± 15%) than Zn (150 ± 9.5%), in relation to control value (100%). The metals effect was reversed after incubation with the amiloride analogue, EIPA, a selective Na + /H + exchanger (NHE) inhibitor as well as in the presence of calphostin C, a protein kinase C (PKC) inhibitor. The heavy metals effect on ·O 2 - production was mediated via the interaction of metal ions with α 1 - and β-adrenergic receptors, as shown after incubation with their respective agonists and antagonists. In addition, both metals caused an increase in intracellular pH (pHi) of gill cells. EIPA together with either metal significantly reduced the effect of each metal treatment on pHi. Incubation of gill cells with the oxidants rotenone, antimycin A and pyruvate caused a significant increase in pHi (ΔpHi 0.830, 0.272 and 0.610, respectively), while in the presence of the anti-oxidant N-acetyl cysteine (NAC) a decrease in pHi (ΔpHi -0.090) was measured, indicating that change in reactive oxygen species (ROS) production by heavy metals affects NHE activity. When rosiglitazone was incubated together with either heavy metal a decrease in O 2 - production was observed. Our results show a key role of NHE in the signal transduction pathway induced by Zn and Cd in gill cells, with the involvement of ROS, PKC, adrenergic and PPAR-γ receptors. In addition, differences between the two metals concerning NHE activation, O 2 - production and interaction with adrenergic receptors were observed

  9. Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages

    Directory of Open Access Journals (Sweden)

    Dimitri Vanhecke

    2017-11-01

    Full Text Available Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line were incubated with gold (AuNPs and iron oxide nanoparticles (FeOxNPs either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeOxNPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase. This increase was higher for both AuNPs and FeOxNPs during co-exposure. Cells treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for the delivery of pharmaceutical agents, this can be beneficial. However, co-exposure should also be taken into account in the case of risk assessment of occupational settings. The demonstration of co-exposure-invoked pathway interactions reveals that synergetic nanoparticle effects, either positive or negative, must be considered for nanotechnology and nanomedicine in particular to develop to its full potential.

  10. The asymmetric binding of PGC-1α to the ERRα and ERRγ nuclear receptor homodimers involves a similar recognition mechanism.

    Directory of Open Access Journals (Sweden)

    Maria Takacs

    Full Text Available PGC-1α is a crucial regulator of cellular metabolism and energy homeostasis that functionally acts together with the estrogen-related receptors (ERRα and ERRγ in the regulation of mitochondrial and metabolic gene networks. Dimerization of the ERRs is a pre-requisite for interactions with PGC-1α and other coactivators, eventually leading to transactivation. It was suggested recently (Devarakonda et al that PGC-1α binds in a strikingly different manner to ERRγ ligand-binding domains (LBDs compared to its mode of binding to ERRα and other nuclear receptors (NRs, where it interacts directly with the two ERRγ homodimer subunits.Here, we show that PGC-1α receptor interacting domain (RID binds in an almost identical manner to ERRα and ERRγ homodimers. Microscale thermophoresis demonstrated that the interactions between PGC-1α RID and ERR LBDs involve a single receptor subunit through high-affinity, ERR-specific L3 and low-affinity L2 interactions. NMR studies further defined the limits of PGC-1α RID that interacts with ERRs. Consistent with these findings, the solution structures of PGC-1α/ERRα LBDs and PGC-1α/ERRγ LBDs complexes share an identical architecture with an asymmetric binding of PGC-1α to homodimeric ERR.These studies provide the molecular determinants for the specificity of interactions between PGC-1α and the ERRs, whereby negative cooperativity prevails in the binding of the coactivators to these receptors. Our work indicates that allosteric regulation may be a general mechanism controlling the binding of the coactivators to homodimers.

  11. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Directory of Open Access Journals (Sweden)

    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  12. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Science.gov (United States)

    Borges, Cibele S; Missassi, Gabriela; Pacini, Enio S A; Kiguti, Luiz Ricardo A; Sanabria, Marciana; Silva, Raquel F; Banzato, Thais P; Perobelli, Juliana E; Pupo, André S; Kempinas, Wilma G

    2013-01-01

    Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors

  13. Mechanisms involved in the hydrothermal growth of ultra-thin and high aspect ratio ZnO nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Demes, Thomas [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Ternon, Céline, E-mail: celine.ternon@grenoble-inp.fr [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Univ. Grenoble Alpes, CNRS, LTM, F-38000 Grenoble (France); Morisot, Fanny [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Univ. Grenoble Alpes, CNRS, Grenoble-INP" 2, IMEP-LaHC, F-38000 Grenoble (France); Riassetto, David [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Legallais, Maxime [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Univ. Grenoble Alpes, CNRS, Grenoble-INP" 2, IMEP-LaHC, F-38000 Grenoble (France); Roussel, Hervé; Langlet, Michel [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France)

    2017-07-15

    Highlights: • ZnO nanowires are grown on sol-gel ZnO seed layers by hydrothermal synthesis. • Ultra-thin and high aspect ratio nanowires are obtained without using additives. • Nanowire diameter is 20–25 nm regardless of growth time and seed morphology. • A nanowire growth model is developed on the basis of thermodynamic considerations. • The nanowires are intended for integration into electrically conductive nanonets. - Abstract: Hydrothermal synthesis of ZnO nanowires (NWs) with tailored dimensions, notably high aspect ratios (AR) and small diameters, is a major concern for a wide range of applications and still represents a challenging and recurring issue. In this work, an additive-free and reproducible hydrothermal procedure has been developed to grow ultra-thin and high AR ZnO NWs on sol-gel deposited ZnO seed layers. Controlling the substrate temperature and using a low reagent concentration (1 mM) has been found to be essential for obtaining such NWs. We show that the NW diameter remains constant at about 20–25 nm with growth time contrary to the NW length that can be selectively increased leading to NWs with ARs up to 400. On the basis of investigated experimental conditions along with thermodynamic and kinetic considerations, a ZnO NW growth mechanism has been developed which involves the formation and growth of nuclei followed by NW growth when the nuclei reach a critical size of about 20–25 nm. The low reagent concentration inhibits NW lateral growth leading to ultra-thin and high AR NWs. These NWs have been assembled into electrically conductive ZnO nanowire networks, which opens attractive perspectives toward the development of highly sensitive low-cost gas- or bio-sensors.

  14. Applying evolutionary anthropology.

    Science.gov (United States)

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. © 2015 Wiley Periodicals, Inc.

  15. Applying Evolutionary Anthropology

    Science.gov (United States)

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. PMID:25684561

  16. Structured synthesis of MEMS using evolutionary approaches

    DEFF Research Database (Denmark)

    Fan, Zhun; Wang, Jiachuan; Achiche, Sofiane

    2008-01-01

    In this paper, we discuss the hierarchy that is involved in a typical MEMS design and how evolutionary approaches can be used to automate the hierarchical synthesis process for MEMS. The paper first introduces the flow of a structured MEMS design process and emphasizes that system-level lumped...

  17. Archaeogenetics in evolutionary medicine.

    Science.gov (United States)

    Bouwman, Abigail; Rühli, Frank

    2016-09-01

    Archaeogenetics is the study of exploration of ancient DNA (aDNA) of more than 70 years old. It is an important part of the wider studies of many different areas of our past, including animal, plant and pathogen evolution and domestication events. Hereby, we address specifically the impact of research in archaeogenetics in the broader field of evolutionary medicine. Studies on ancient hominid genomes help to understand even modern health patterns. Human genetic microevolution, e.g. related to abilities of post-weaning milk consumption, and specifically genetic adaptation in disease susceptibility, e.g. towards malaria and other infectious diseases, are of the upmost importance in contributions of archeogenetics on the evolutionary understanding of human health and disease. With the increase in both the understanding of modern medical genetics and the ability to deep sequence ancient genetic information, the field of archaeogenetic evolutionary medicine is blossoming.

  18. Towards unified characterization of cooperation mechanisms. Comment on "Universal scaling for the dilemma strength in evolutionary games" by Z. Wang et al.

    Science.gov (United States)

    Han, The Anh

    2015-09-01

    "I will jump into the river to save two brothers or eight cousins": This famous quote by J.B.S. Haldane accurately anticipates the conditions under which cooperation is the favorable choice in an interaction between genetic relatives. The general condition can later be formulated as a surprisingly simple mathematical expression, known as the Hamilton's rule, stating that natural selection favors cooperation if the genetic relatedness (r) between the donor and the recipient of a cooperative act is greater than its cost (c) to benefit (b) ratio [1]: r > c / b. Motivated by Hamilton's elegant early studies, researchers have attempted to find simple and concise rules that characterize the conditions for cooperation to be selected under various social viscosity [2,3]. For example, the seminal work by M. Nowak [3] in 2006 shows that similarly simple rules can be derived that govern each of the other four popular mechanisms of cooperation-direct reciprocity, indirect reciprocity, group selection and network reciprocity-, which can be expressed via the cost-to-benefit ratio being smaller than some critical value associated with the mechanism at work (as seen, for kin interactions, the critical value is relatedness). However, these rules are restricted to the donor and recipient (D&R) paradigm. The question is thus whether it is possible to obtain simple rules even for the general case? The answer is not trivial as a general two-player game is described by four independent parameters, not just two as in the D&R game.

  19. Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound

    Directory of Open Access Journals (Sweden)

    João Batista Gadelha de Cerqueira

    2012-10-01

    Full Text Available PURPOSE: The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH34(caffeine(NO]C13 (Rut-Caf and sodium nitroprusside (SNP. MATERIALS AND METHODS: The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE (1 µM and then concentration-response curves (10-12 - 10-4 M were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM, oxyhemoglobin (10 µM, L-cysteine (100 µM, hydroxicobalamine (100 µM, glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced. RESULTS: The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50 and maximum effect (Emax. The substances showed activity through activation of the soluble guanylyl cyclase (sGC, because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L-cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09. There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process. CONCLUSIONS: In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.

  20. A Double Evolutionary Pool Memetic Algorithm for Examination Timetabling Problems

    Directory of Open Access Journals (Sweden)

    Yu Lei

    2014-01-01

    Full Text Available A double evolutionary pool memetic algorithm is proposed to solve the examination timetabling problem. To improve the performance of the proposed algorithm, two evolutionary pools, that is, the main evolutionary pool and the secondary evolutionary pool, are employed. The genetic operators have been specially designed to fit the examination timetabling problem. A simplified version of the simulated annealing strategy is designed to speed the convergence of the algorithm. A clonal mechanism is introduced to preserve population diversity. Extensive experiments carried out on 12 benchmark examination timetabling instances show that the proposed algorithm is able to produce promising results for the uncapacitated examination timetabling problem.

  1. A chromatin modifying enzyme, SDG8, is involved in morphological, gene expression, and epigenetic responses to mechanical stimulation

    OpenAIRE

    Cazzonelli, Christopher I.; Nisar, Nazia; Roberts, Andrea C.; Murray, Kevin D.; Borevitz, Justin O.; Pogson, Barry J.

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzym...

  2. EVOLUTIONARY FOUNDATIONS FOR MOLECULAR MEDICINE

    Science.gov (United States)

    Nesse, Randolph M.; Ganten, Detlev; Gregory, T. Ryan; Omenn, Gilbert S.

    2015-01-01

    Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more opportunities for progress at the interface of evolution with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and others to speed the development of evolutionary molecular medicine. PMID:22544168

  3. Evolutionary Sound Synthesis Controlled by Gestural Data

    Directory of Open Access Journals (Sweden)

    Jose Fornari

    2011-05-01

    Full Text Available This article focuses on the interdisciplinary research involving Computer Music and Generative Visual Art. We describe the implementation of two interactive artistic systems based on principles of Gestural Data (WILSON, 2002 retrieval and self-organization (MORONI, 2003, to control an Evolutionary Sound Synthesis method (ESSynth. The first implementation uses, as gestural data, image mapping of handmade drawings. The second one uses gestural data from dynamic body movements of dance. The resulting computer output is generated by an interactive system implemented in Pure Data (PD. This system uses principles of Evolutionary Computation (EC, which yields the generation of a synthetic adaptive population of sound objects. Considering that music could be seen as “organized sound” the contribution of our study is to develop a system that aims to generate "self-organized sound" – a method that uses evolutionary computation to bridge between gesture, sound and music.

  4. Evolutionary dynamics of complex communications networks

    CERN Document Server

    Karyotis, Vasileios; Papavassiliou, Symeon

    2013-01-01

    Until recently, most network design techniques employed a bottom-up approach with lower protocol layer mechanisms affecting the development of higher ones. This approach, however, has not yielded fascinating results in the case of wireless distributed networks. Addressing the emerging aspects of modern network analysis and design, Evolutionary Dynamics of Complex Communications Networks introduces and develops a top-bottom approach where elements of the higher layer can be exploited in modifying the lowest physical topology-closing the network design loop in an evolutionary fashion similar to

  5. Evolutionary trends in Heteroptera

    NARCIS (Netherlands)

    Cobben, R.H.

    1968-01-01

    1. This work, the first volume of a series dealing with evolutionary trends in Heteroptera, is concerned with the egg system of about 400 species. The data are presented systematically in chapters 1 and 2 with a critical review of the literature after each family.

    2. Chapter 3 evaluates facts

  6. Evolutionary mysteries in meiosis

    NARCIS (Netherlands)

    Lenormand, Thomas; Engelstädter, Jan; Johnston, Susan E.; Wijnker, Erik; Haag, Christoph R.

    2016-01-01

    Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these

  7. Applications of Evolutionary Computation

    NARCIS (Netherlands)

    Mora, Antonio M.; Squillero, Giovanni; Di Chio, C; Agapitos, Alexandros; Cagnoni, Stefano; Cotta, Carlos; Fernández De Vega, F; Di Caro, G A; Drechsler, R.; Ekárt, A; Esparcia-Alcázar, Anna I.; Farooq, M; Langdon, W B; Merelo-Guervós, J.J.; Preuss, M; Richter, O.-M.H.; Silva, Sara; Sim$\\$~oes, A; Squillero, Giovanni; Tarantino, Ernesto; Tettamanzi, Andrea G B; Togelius, J; Urquhart, Neil; Uyar, A S; Yannakakis, G N; Smith, Stephen L; Caserta, Marco; Ramirez, Adriana; Voß, Stefan; Squillero, Giovanni; Burelli, Paolo; Mora, Antonio M.; Squillero, Giovanni; Jan, Mathieu; Matthias, M; Di Chio, C; Agapitos, Alexandros; Cagnoni, Stefano; Cotta, Carlos; Fernández De Vega, F; Di Caro, G A; Drechsler, R.; Ekárt, A; Esparcia-Alcázar, Anna I.; Farooq, M; Langdon, W B; Merelo-Guervós, J.J.; Preuss, M; Richter, O.-M.H.; Silva, Sara; Sim$\\$~oes, A; Squillero, Giovanni; Tarantino, Ernesto; Tettamanzi, Andrea G B; Togelius, J; Urquhart, Neil; Uyar, A S; Yannakakis, G N; Caserta, Marco; Ramirez, Adriana; Voß, Stefan; Squillero, Giovanni; Burelli, Paolo; Esparcia-Alcazar, Anna I; Silva, Sara; Agapitos, Alexandros; Cotta, Carlos; De Falco, Ivanoe; Cioppa, Antonio Della; Diwold, Konrad; Ekart, Aniko; Tarantino, Ernesto; Vega, Francisco Fernandez De; Burelli, Paolo; Sim, Kevin; Cagnoni, Stefano; Simoes, Anabela; Merelo, J.J.; Urquhart, Neil; Haasdijk, Evert; Zhang, Mengjie; Squillero, Giovanni; Eiben, A E; Tettamanzi, Andrea G B; Glette, Kyrre; Rohlfshagen, Philipp; Schaefer, Robert; Caserta, Marco; Ramirez, Adriana; Voß, Stefan

    2015-01-01

    The application of genetic and evolutionary computation to problems in medicine has increased rapidly over the past five years, but there are specific issues and challenges that distinguish it from other real-world applications. Obtaining reliable and coherent patient data, establishing the clinical

  8. Evolutionary perspectives on ageing.

    Science.gov (United States)

    Reichard, Martin

    2017-10-01

    From an evolutionary perspective, ageing is a decrease in fitness with chronological age - expressed by an increase in mortality risk and/or decline in reproductive success and mediated by deterioration of functional performance. While this makes ageing intuitively paradoxical - detrimental to individual fitness - evolutionary theory offers answers as to why ageing has evolved. In this review, I first briefly examine the classic evolutionary theories of ageing and their empirical tests, and highlight recent findings that have advanced our understanding of the evolution of ageing (condition-dependent survival, positive pleiotropy). I then provide an overview of recent theoretical extensions and modifications that accommodate those new discoveries. I discuss the role of indeterminate (asymptotic) growth for lifetime increases in fecundity and ageing trajectories. I outline alternative views that challenge a universal existence of senescence - namely the lack of a germ-soma distinction and the ability of tissue replacement and retrogression to younger developmental stages in modular organisms. I argue that rejuvenation at the organismal level is plausible, but includes a return to a simple developmental stage. This may exempt a particular genotype from somatic defects but, correspondingly, removes any information acquired during development. A resolution of the question of whether a rejuvenated individual is the same entity is central to the recognition of whether current evolutionary theories of ageing, with their extensions and modifications, can explain the patterns of ageing across the Tree of Life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Editorial overview: Evolutionary psychology

    NARCIS (Netherlands)

    Gangestad, S.W.; Tybur, J.M.

    2016-01-01

    Functional approaches in psychology - which ask what behavior is good for - are almost as old as scientific psychology itself. Yet sophisticated, generative functional theories were not possible until developments in evolutionary biology in the mid-20th century. Arising in the last three decades,

  10. Biochemistry and evolutionary biology

    Indian Academy of Sciences (India)

    Biochemical information has been crucial for the development of evolutionary biology. On the one hand, the sequence information now appearing is producing a huge increase in the amount of data available for phylogenetic analysis; on the other hand, and perhaps more fundamentally, it allows understanding of the ...

  11. Evolutionary Biology Today

    Indian Academy of Sciences (India)

    Hindi and English. Port 1. Resonance, Vo1.7 ... they use. Of course, many evolutionary biologists do work with fossils or DNA, or both, but there are also large numbers of ... The first major division that I like to make is between studies focussed ...

  12. Learning: An Evolutionary Analysis

    Science.gov (United States)

    Swann, Joanna

    2009-01-01

    This paper draws on the philosophy of Karl Popper to present a descriptive evolutionary epistemology that offers philosophical solutions to the following related problems: "What happens when learning takes place?" and "What happens in human learning?" It provides a detailed analysis of how learning takes place without any direct transfer of…

  13. Complex systems, evolutionary planning?

    NARCIS (Netherlands)

    Bertolini, L.; de Roo, G.; Silva, E.A.

    2010-01-01

    Coping with uncertainty is a defining challenge for spatial planners. Accordingly, most spatial planning theories and methods are aimed at reducing uncertainty. However, the question is what should be done when this seems impossible? This chapter proposes an evolutionary interpretation of spatial

  14. Molluscan Evolutionary Development

    DEFF Research Database (Denmark)

    Wanninger, Andreas Wilhelm Georg; Koop, Damien; Moshel-Lynch, Sharon

    2008-01-01

    Brought together by Winston F. Ponder and David R. Lindberg, thirty-six experts on the evolution of the Mollusca provide an up-to-date review of its evolutionary history. The Mollusca are the second largest animal phylum and boast a fossil record of over 540 million years. They exhibit remarkable...

  15. An Evolutionary Psychology Approach to Consumer Choice

    Directory of Open Access Journals (Sweden)

    ZURINA BT MOHAIDIN

    2013-07-01

    Full Text Available Human behaviour can be explained not only through experience and environments but also by incorporating evolutionary explanation. Consumer behaviour could not be understood accurately without infusing Darwinian evolutionary theory which has contributed in the knowledge of human nature. Evolutionary psychology revolves around the human’s evolved mental and the impact on human’s traits and behaviour where the influence of the environment to our genes would determine our individual behaviour and traits, resulting in variation among us. Foraging which is a part of behavioural ecology involves many sequences or repetitions of animals’ activities and decision making which is useful to relate these patterns of activities to the decisions made in human consumption. The aim of this research is to investigate the similarities of human consumption and ecological behaviour by employing interpretative and comparative approach. It is hoped that by applying the evolutionary theory in explaining consumer choice, this study is able to contribute to the development of behavioural ecology in human consumption. The analysis of the data is done aggregately for 200 consumers and individually for 20 consumers, who have purchased four product categories over a year. This study concludes that the theories of evolutionary psychology can fit to the consumers’ buying behaviour implicating its usefulness in explaining the consumers’ choice.

  16. Characterization and evolutionary analysis of tributyltin-binding protein and pufferfish saxitoxin and tetrodotoxin-binding protein genes in toxic and nontoxic pufferfishes.

    Science.gov (United States)

    Hashiguchi, Y; Lee, J M; Shiraishi, M; Komatsu, S; Miki, S; Shimasaki, Y; Mochioka, N; Kusakabe, T; Oshima, Y

    2015-05-01

    Understanding the evolutionary mechanisms of toxin accumulation in pufferfishes has been long-standing problem in toxicology and evolutionary biology. Pufferfish saxitoxin and tetrodotoxin-binding protein (PSTBP) is involved in the transport and accumulation of tetrodotoxin and is one of the most intriguing proteins related to the toxicity of pufferfishes. PSTBPs are fusion proteins consisting of two tandem repeated tributyltin-binding protein type 2 (TBT-bp2) domains. In this study, we examined the evolutionary dynamics of TBT-bp2 and PSTBP genes to understand the evolution of toxin accumulation in pufferfishes. Database searches and/or PCR-based cDNA cloning in nine pufferfish species (6 toxic and 3 nontoxic) revealed that all species possessed one or more TBT-bp2 genes, but PSTBP genes were found only in 5 toxic species belonging to genus Takifugu. These toxic Takifugu species possessed two or three copies of PSTBP genes. Phylogenetic analysis of TBT-bp2 and PSTBP genes suggested that PSTBPs evolved in the common ancestor of Takifugu species by repeated duplications and fusions of TBT-bp2 genes. In addition, a detailed comparison of Takifugu TBT-bp2 and PSTBP gene sequences detected a signature of positive selection under the pressure of gene conversion. The complicated evolutionary dynamics of TBT-bp2 and PSTBP genes may reflect the diversity of toxicity in pufferfishes. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  17. Evolutionary genomics and HIV restriction factors.

    Science.gov (United States)

    Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

    2015-03-01

    To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

  18. Opioid Mechanism Involvement in the Synergism Produced by the Combination of Diclofenac and Caffeine in the Formalin Model

    OpenAIRE

    Flores-Ramos, Jos? Mar?a; D?az-Reval, M. Irene

    2013-01-01

    Analgesics can be administered in combination with caffeine for improved analgesic effectiveness in a process known as synergism. The mechanisms by which these combinations produce synergism are not yet fully understood. The aim of this study was to analyze whether the administration of diclofenac combined with caffeine produced antinociceptive synergism and whether opioid mechanisms played a role in this event. The formalin model was used to evaluate the antinociception produced by the oral ...

  19. Origin of evolutionary change in avian clutch size.

    Science.gov (United States)

    Haywood, Sacha

    2013-11-01

    Why different bird species lay different numbers of eggs is a question that has long been associated with factors external to the organism, that is, factors which operate on inherited variation in clutch size through the action of natural selection. Yet, while external factors are important, the extent of what is evolutionarily possible rests with the mechanisms developed by birds for clutch-size control. Hitherto neglected, these mechanisms generate factors internal to the organism that are central to the origin of evolutionary change. They are related to the fact that a species-specific range of clutch size arises from the differential survival of pre-ovulatory follicles undergoing growth when the signal causing egg laying to end reaches the ovary. Herein, I examine three internal factors that, together with external factors, could impact the evolution of avian clutch size. Each factor acts by changing either the number of pre-ovulatory follicles present in the ovary at the time of follicular disruption or the timing of this event. These changes to clutch size can be explained by the concept of heterochrony. In light of this, the role of phenotypic plasticity and genes determining clutch size is discussed. Finally, to account for the origin of evolutionary change in clutch size, I detail an hypothesis involving a process similar to Waddington's theory of genetic assimilation. © 2013 The Author. Biological Reviews © 2013 Cambridge Philosophical Society.

  20. Involvement of protein kinase C in the mechanism of action of Escherichia coli heat-stable enterotoxin (STa) in a human colonic carcinoma cell line, COLO-205

    International Nuclear Information System (INIS)

    Gupta, Dyuti Datta; Saha, Subhrajit; Chakrabarti, Manoj K.

    2005-01-01

    The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP 3 -mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKCα) was specified using isotype-specific pseudosubstrate, which showed pronounce enzyme activity. Inhibition of enzyme activity by PKCα-specific inhibitor Goe6976 and immunoblott study employing isotype-specific antibody further demonstrated the involvement of calcium-dependent isoform of PKC in the mechanism of action of E. coli STa. Moreover, inhibition of guanylate cyclase activity by PKCα-specific inhibitor Goe6976 suggested the involvement of PKCα in the regulation of guanylate cyclase activity

  1. Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

    Science.gov (United States)

    Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

    2017-04-01

    Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

  2. Markov Networks in Evolutionary Computation

    CERN Document Server

    Shakya, Siddhartha

    2012-01-01

    Markov networks and other probabilistic graphical modes have recently received an upsurge in attention from Evolutionary computation community, particularly in the area of Estimation of distribution algorithms (EDAs).  EDAs have arisen as one of the most successful experiences in the application of machine learning methods in optimization, mainly due to their efficiency to solve complex real-world optimization problems and their suitability for theoretical analysis. This book focuses on the different steps involved in the conception, implementation and application of EDAs that use Markov networks, and undirected models in general. It can serve as a general introduction to EDAs but covers also an important current void in the study of these algorithms by explaining the specificities and benefits of modeling optimization problems by means of undirected probabilistic models. All major developments to date in the progressive introduction of Markov networks based EDAs are reviewed in the book. Hot current researc...

  3. An extrahepatic receptor-associated protein-sensitive mechanism is involved in the metabolism of triglyceride-rich lipoproteins

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Rohlmann, A.; Page, S.T.; Bensadoun, A.; Bos, I.S.T.; Berkel, T.J.C. van; Havekes, L.M.; Herz, J.

    1999-01-01

    We have used adenovirus-mediated gene transfer in mice to investigate low density lipoprotein receptor (LDLR) and LDLR-related protein (LRP)- independent mechanisms that control the metabolism of chylomicron and very low density lipoprotein (VLDL) remnants in vivo. Overexpression of receptor-

  4. Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

    Science.gov (United States)

    Pingel, Jessica; Suhr, Frank

    2017-08-01

    Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young and adults. Muscle contractures are characterized by gradually increasing passive muscle stiffness resulting in complete fixation of joints. Different mechanisms have been identified in CP-related contractures, i.e. altered calcium handling, altered metabolism or altered titin regulation. The muscle-related extracellular matrix (ECM), specifically collagens, plays a role in CP-related contractures. Herein, we focus on mechanically sensitive complexes, known as costameres (Cstms), and discuss their potential role in CP-related contractures. We extend our discussion to the ECM due to the limited knowledge of its role in CP-related contractures. The aims of this review are (1) to summarize CP-related contracture mechanisms, (2) to raise novel hypotheses on the genesis of contractures with a focus on Cstms, and (3) to stimulate novel approaches to study CP-related contractures.

  5. A chromatin modifying enzyme, SDG8, is involved in morphological, gene expression, and epigenetic responses to mechanical stimulation.

    Science.gov (United States)

    Cazzonelli, Christopher I; Nisar, Nazia; Roberts, Andrea C; Murray, Kevin D; Borevitz, Justin O; Pogson, Barry J

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzyme, SDG8/ASHH2, which can regulate the expression of many touch responsive genes identified in Arabidopsis. SDG8 is required for the permissive expression of touch induced genes; and the loss of function of sdg8 perturbs the maximum levels of induction on selected touch gene targets. SDG8 is required to maintain permissive H3K4 trimethylation marks surrounding the Arabidopsis touch-inducible gene TOUCH 3 (TCH3), which encodes a calmodulin-like protein (CML12). The gene neighboring was also slightly down regulated, revealing a new target for SDG8 mediated chromatin modification. Finally, sdg8 mutants show perturbed morphological response to wind-agitated mechanical stimuli, implicating an epigenetic memory-forming process in the acclimation response of thigmomorphogenesis.

  6. Positive effect of Chang Run Tong on colonic remodeling in streptozotocin-induced diabetic rats and mechanisms involved

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Sha, Hong; Gregersen, Hans

    2015-01-01

    Objective: It has been documented that the Chinese medicine Chang Run Tong (CRT) has a positive effect on constipation which is a prominent symptom in diabetic patients. This present study investigated the effect and the possible mechanism of CRT on colonic remodeling in streptozotocin (STZ...

  7. Autophosphorylation of [alpha]CaMKII is Differentially Involved in New Learning and Unlearning Mechanisms of Memory Extinction

    Science.gov (United States)

    Kimura, Ryoichi; Silva, Alcino J.; Ohno, Masuo

    2008-01-01

    Accumulating evidence indicates the key role of [alpha]-calcium/calmodulin-dependent protein kinase II ([alpha]CaMKII) in synaptic plasticity and learning, but it remains unclear how this kinase participates in the processing of memory extinction. Here, we investigated the mechanism by which [alpha]CaMKII may mediate extinction by using…

  8. Introduction to Evolutionary Algorithms

    CERN Document Server

    Yu, Xinjie

    2010-01-01

    Evolutionary algorithms (EAs) are becoming increasingly attractive for researchers from various disciplines, such as operations research, computer science, industrial engineering, electrical engineering, social science, economics, etc. This book presents an insightful, comprehensive, and up-to-date treatment of EAs, such as genetic algorithms, differential evolution, evolution strategy, constraint optimization, multimodal optimization, multiobjective optimization, combinatorial optimization, evolvable hardware, estimation of distribution algorithms, ant colony optimization, particle swarm opti

  9. Biochemical mechanisms involved in the endotoxin-induced type II cell hyperplasia in F344 rat lung

    International Nuclear Information System (INIS)

    Tesfaigzi, J.; Johnson, N.F.; Lechner, J.F.

    1994-01-01

    Proliferative lesions and pulmonary epithelial neoplasms induced in the rat by plutonium inhalation have been shown to be of type II cell origin. Defining the gene changes responsible for the development of the type II proliferative lesions would help to elucidate the genetic events involved in the expansion of initiated type II cells into fully transformed tumor cells. One problem in identifying these gene alterations is dissociating changes in gene expression linked to cell replication or repair from those involved in tumor initiation and progression. The long-term goals of these investigations are to first develop and characterize a model of transient type II cell hyperplasia. Second, changes in gene expression associated with remodeling epithelium will be compared to gene changes exhibited by the 239 Pu-induced hyperplastic lesions

  10. Evolutionary games on graphs

    Science.gov (United States)

    Szabó, György; Fáth, Gábor

    2007-07-01

    Game theory is one of the key paradigms behind many scientific disciplines from biology to behavioral sciences to economics. In its evolutionary form and especially when the interacting agents are linked in a specific social network the underlying solution concepts and methods are very similar to those applied in non-equilibrium statistical physics. This review gives a tutorial-type overview of the field for physicists. The first four sections introduce the necessary background in classical and evolutionary game theory from the basic definitions to the most important results. The fifth section surveys the topological complications implied by non-mean-field-type social network structures in general. The next three sections discuss in detail the dynamic behavior of three prominent classes of models: the Prisoner's Dilemma, the Rock-Scissors-Paper game, and Competing Associations. The major theme of the review is in what sense and how the graph structure of interactions can modify and enrich the picture of long term behavioral patterns emerging in evolutionary games.

  11. Evolutionary mysteries in meiosis.

    Science.gov (United States)

    Lenormand, Thomas; Engelstädter, Jan; Johnston, Susan E; Wijnker, Erik; Haag, Christoph R

    2016-10-19

    Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often 'weird' features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'. © 2016 The Author(s).

  12. Asymmetric Evolutionary Games

    Science.gov (United States)

    McAvoy, Alex; Hauert, Christoph

    2015-01-01

    Evolutionary game theory is a powerful framework for studying evolution in populations of interacting individuals. A common assumption in evolutionary game theory is that interactions are symmetric, which means that the players are distinguished by only their strategies. In nature, however, the microscopic interactions between players are nearly always asymmetric due to environmental effects, differing baseline characteristics, and other possible sources of heterogeneity. To model these phenomena, we introduce into evolutionary game theory two broad classes of asymmetric interactions: ecological and genotypic. Ecological asymmetry results from variation in the environments of the players, while genotypic asymmetry is a consequence of the players having differing baseline genotypes. We develop a theory of these forms of asymmetry for games in structured populations and use the classical social dilemmas, the Prisoner’s Dilemma and the Snowdrift Game, for illustrations. Interestingly, asymmetric games reveal essential differences between models of genetic evolution based on reproduction and models of cultural evolution based on imitation that are not apparent in symmetric games. PMID:26308326

  13. Evolutionary dynamics of incubation periods.

    Science.gov (United States)

    Ottino-Loffler, Bertrand; Scott, Jacob G; Strogatz, Steven H

    2017-12-21

    The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dynamics on graphs. For simple models of a mutant or pathogen invading a network-structured population of healthy cells, we show that skewed distributions of incubation periods emerge for a wide range of assumptions about invader fitness, competition dynamics, and network structure. The skewness stems from stochastic mechanisms associated with two classic problems in probability theory: the coupon collector and the random walk. Unlike previous explanations that rely crucially on heterogeneity, our results hold even for homogeneous populations. Thus, we predict that two equally healthy individuals subjected to equal doses of equally pathogenic agents may, by chance alone, show remarkably different time courses of disease.

  14. Evolutionary adaptations to dietary changes.

    Science.gov (United States)

    Luca, F; Perry, G H; Di Rienzo, A

    2010-08-21

    Through cultural innovation and changes in habitat and ecology, there have been a number of major dietary shifts in human evolution, including meat eating, cooking, and those associated with plant and animal domestication. The identification of signatures of adaptations to such dietary changes in the genome of extant primates (including humans) may shed light not only on the evolutionary history of our species, but also on the mechanisms that underlie common metabolic diseases in modern human populations. In this review, we provide a brief overview of the major dietary shifts that occurred during hominin evolution, and we discuss the methods and approaches used to identify signals of natural selection in patterns of sequence variation. We then review the results of studies aimed at detecting the genetic loci that played a major role in dietary adaptations and conclude by outlining the potential of future studies in this area.

  15. Immune Response Induction and New Effector Mechanisms Possibly Involved in Protection Conferred by the Cuban Anti-Meningococcal BC Vaccine

    Science.gov (United States)

    Pérez, Oliver; Lastre, Miriam; Lapinet, José; Bracho, Gustavo; Díaz, Miriam; Zayas, Caridad; Taboada, Carlos; Sierra, Gustavo

    2001-01-01

    This report explores the participation of some afferent mechanisms in the immune response induced by the Cuban anti-meningococcal vaccine VA-MENGOC-BC. The induction of delayed-type hypersensitivity in nursing babies and lymphocyte proliferation after immunization is demonstrated. The presence of gamma interferon IFN-γ and interleukin-2 (IL-2) mRNAs but absence of IL-4, IL-5, and IL-10 mRNAs were observed in peripheral blood mononuclear cells from immunized subjects after in vitro challenge with outer membrane vesicles. In addition, some effector functions were also explored. The presence of opsonic activity was demonstrated in sera from vaccinees. The role of neutrophils as essential effector cells was shown. In conclusion, we have shown that, at least in the Cuban adult population, VA-MENGOC-BC induces mechanisms with a T-helper 1 pattern in the afferent and effector branches of the immune response. PMID:11401992

  16. Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone

    Directory of Open Access Journals (Sweden)

    Sergio Perez-Alvarez

    2012-01-01

    Full Text Available Previously, we have shown that SH-SY5Y cells exposed to high concentrations of methadone died due to a necrotic-like cell death mechanism related to delayed calcium deregulation (DCD. In this study, we show that, in terms of their Ca2+ responses to 0.5 mM methadone, SH-SY5Y cells can be pooled into four different groups. In a broad pharmacological survey, the relevance of different Ca2+-related mechanisms on methadone-induced DCD was investigated including extracellular calcium, L-type Ca2+ channels, μ-opioid receptor, mitochondrial inner membrane potential, mitochondrial ATP synthesis, mitochondrial Ca2+/2Na+-exchanger, reactive oxygen species, and mitochondrial permeability transition. Only those compounds targeting mitochondria such as oligomycin, FCCP, CGP 37157, and cyclosporine A were able to amend methadone-induced Ca2+ dyshomeostasis suggesting that methadone induces DCD by modulating the ability of mitochondria to handle Ca2+. Consistently, mitochondria became dramatically shorter and rounder in the presence of methadone. Furthermore, analysis of oxygen uptake by isolated rat liver mitochondria suggested that methadone affected mitochondrial Ca2+ uptake in a respiratory substrate-dependent way. We conclude that methadone causes failure of intracellular Ca2+ homeostasis, and this effect is associated with morphological and functional changes of mitochondria. Likely, this mechanism contributes to degenerative side effects associated with methadone treatment.

  17. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

    Science.gov (United States)

    Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-03-13

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h -1 ) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch -1 ) seeds (P  0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

  18. Timely activation of budding yeast APCCdh1 involves degradation of its inhibitor, Acm1, by an unconventional proteolytic mechanism.

    Directory of Open Access Journals (Sweden)

    Michael Melesse

    Full Text Available Regulated proteolysis mediated by the ubiquitin proteasome system is a fundamental and essential feature of the eukaryotic cell division cycle. Most proteins with cell cycle-regulated stability are targeted for degradation by one of two related ubiquitin ligases, the Skp1-cullin-F box protein (SCF complex or the anaphase-promoting complex (APC. Here we describe an unconventional cell cycle-regulated proteolytic mechanism that acts on the Acm1 protein, an inhibitor of the APC activator Cdh1 in budding yeast. Although Acm1 can be recognized as a substrate by the Cdc20-activated APC (APCCdc20 in anaphase, APCCdc20 is neither necessary nor sufficient for complete Acm1 degradation at the end of mitosis. An APC-independent, but 26S proteasome-dependent, mechanism is sufficient for complete Acm1 clearance from late mitotic and G1 cells. Surprisingly, this mechanism appears distinct from the canonical ubiquitin targeting pathway, exhibiting several features of ubiquitin-independent proteasomal degradation. For example, Acm1 degradation in G1 requires neither lysine residues in Acm1 nor assembly of polyubiquitin chains. Acm1 was stabilized though by conditional inactivation of the ubiquitin activating enzyme Uba1, implying some requirement for the ubiquitin pathway, either direct or indirect. We identified an amino terminal predicted disordered region in Acm1 that contributes to its proteolysis in G1. Although ubiquitin-independent proteasome substrates have been described, Acm1 appears unique in that its sensitivity to this mechanism is strictly cell cycle-regulated via cyclin-dependent kinase (Cdk phosphorylation. As a result, Acm1 expression is limited to the cell cycle window in which Cdk is active. We provide evidence that failure to eliminate Acm1 impairs activation of APCCdh1 at mitotic exit, justifying its strict regulation by cell cycle-dependent transcription and proteolytic mechanisms. Importantly, our results reveal that strict cell

  19. Timely Activation of Budding Yeast APCCdh1 Involves Degradation of Its Inhibitor, Acm1, by an Unconventional Proteolytic Mechanism

    Science.gov (United States)

    Melesse, Michael; Choi, Eunyoung; Hall, Hana; Walsh, Michael J.; Geer, M. Ariel; Hall, Mark C.

    2014-01-01

    Regulated proteolysis mediated by the ubiquitin proteasome system is a fundamental and essential feature of the eukaryotic cell division cycle. Most proteins with cell cycle-regulated stability are targeted for degradation by one of two related ubiquitin ligases, the Skp1-cullin-F box protein (SCF) complex or the anaphase-promoting complex (APC). Here we describe an unconventional cell cycle-regulated proteolytic mechanism that acts on the Acm1 protein, an inhibitor of the APC activator Cdh1 in budding yeast. Although Acm1 can be recognized as a substrate by the Cdc20-activated APC (APCCdc20) in anaphase, APCCdc20 is neither necessary nor sufficient for complete Acm1 degradation at the end of mitosis. An APC-independent, but 26S proteasome-dependent, mechanism is sufficient for complete Acm1 clearance from late mitotic and G1 cells. Surprisingly, this mechanism appears distinct from the canonical ubiquitin targeting pathway, exhibiting several features of ubiquitin-independent proteasomal degradation. For example, Acm1 degradation in G1 requires neither lysine residues in Acm1 nor assembly of polyubiquitin chains. Acm1 was stabilized though by conditional inactivation of the ubiquitin activating enzyme Uba1, implying some requirement for the ubiquitin pathway, either direct or indirect. We identified an amino terminal predicted disordered region in Acm1 that contributes to its proteolysis in G1. Although ubiquitin-independent proteasome substrates have been described, Acm1 appears unique in that its sensitivity to this mechanism is strictly cell cycle-regulated via cyclin-dependent kinase (Cdk) phosphorylation. As a result, Acm1 expression is limited to the cell cycle window in which Cdk is active. We provide evidence that failure to eliminate Acm1 impairs activation of APCCdh1 at mitotic exit, justifying its strict regulation by cell cycle-dependent transcription and proteolytic mechanisms. Importantly, our results reveal that strict cell-cycle expression profiles

  20. MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

    Science.gov (United States)

    Verdelli, C; Corbetta, S

    2017-01-01

    Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed. © 2017 European Society of Endocrinology.

  1. The Crystal Structure and Mechanism of an Unusual Oxidoreductase, GilR, Involved in Gilvocarcin V Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bosserman, Mary A.; Schickli, M. Alexandra; Piszczek, Grzegorz; Kharel, Madan K.; Pahari, Pallab; Buchanan, Susan K.; Rohr, Jürgen (NIH); (Kentucky)

    2012-11-26

    GilR is a recently identified oxidoreductase that catalyzes the terminal step of gilvocarcin V biosynthesis and is a unique enzyme that establishes the lactone core of the polyketide-derived gilvocarcin chromophore. Gilvocarcin-type compounds form a small distinct family of anticancer agents that are involved in both photo-activated DNA-alkylation and histone H3 cross-linking. High resolution crystal structures of apoGilR and GilR in complex with its substrate pregilvocarcin V reveals that GilR belongs to the small group of a relatively new type of the vanillyl-alcohol oxidase flavoprotein family characterized by bicovalently tethered cofactors. GilR was found as a dimer, with the bicovalently attached FAD cofactor mediated through His-65 and Cys-125. Subsequent mutagenesis and functional assays indicate that Tyr-445 may be involved in reaction catalysis and in mediating the covalent attachment of FAD, whereas Tyr-448 serves as an essential residue initiating the catalysis by swinging away from the active site to accommodate binding of the 6R-configured substrate and consequently abstracting the proton of the hydroxyl residue of the substrate hemiacetal 6-OH group. These studies lay the groundwork for future enzyme engineering to broaden the substrate specificity of this bottleneck enzyme of the gilvocarcin biosynthetic pathway for the development of novel anti-cancer therapeutics.

  2. Effects of Time-Compressed Speech Training on Multiple Functional and Structural Neural Mechanisms Involving the Left Superior Temporal Gyrus.

    Science.gov (United States)

    Maruyama, Tsukasa; Takeuchi, Hikaru; Taki, Yasuyuki; Motoki, Kosuke; Jeong, Hyeonjeong; Kotozaki, Yuka; Nakagawa, Seishu; Nouchi, Rui; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Sakaki, Kohei; Sasaki, Yukako; Magistro, Daniele; Kawashima, Ryuta

    2018-01-01

    Time-compressed speech is an artificial form of rapidly presented speech. Training with time-compressed speech (TCSSL) in a second language leads to adaptation toward TCSSL. Here, we newly investigated the effects of 4 weeks of training with TCSSL on diverse cognitive functions and neural systems using the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time-compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time-compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension.

  3. Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Shi J

    2016-11-01

    Full Text Available Jinshan Shi,1,* Ke Jiang,2,* Zhaoduan Li,3 1Department of Anesthesiology, Guizhou Provincial People’s Hospital, 2Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 3Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Little is known about the effects of the development of type 2 diabetes on glutamate homeostasis in the spinal cord. Therefore, we quantified the extracellular levels of glutamate in the spinal cord of Zucker diabetic fatty (ZDF rats using in vivo microdialysis. In addition, protein levels of glutamate transporter-1 (GLT-1 in the spinal cord of ZDF rats were measured using Western blot. Finally, the effects of repeated intrathecal injections of ceftriaxone, which was previously shown to enhance GLT-1 expression, on the development of mechanical allodynia and hyperalgesia as well as on basal extracellular level of glutamate and the expression of GLT-1 in the spinal cord of ZDF rats were evaluated. It was found that ZDF rats developed mechanical hyperalgesia and allodynia, which were associated with increased basal extracellular levels of glutamate and attenuated levels of GLT-1 expression in the spinal cord, particularly in the dorsal horn. Furthermore, repeated intrathecal administrations of ceftriaxone dose-dependently prevented the development of mechanical hyperalgesia and allodynia in ZDF rats, which were correlated with enhanced GLT-1 expression without altering the basal glutamate levels in the spinal cord of ZDF rats. Overall, the results suggested that impaired glutamate reuptake in the spinal cord may contribute to the development of neuropathic pains in type 2 diabetes. Keywords: diabetes, peripheral neuropathy, spinal cord, Zucker diabetic fatty rats, glutamate, glutamate transporter-1

  4. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

    Directory of Open Access Journals (Sweden)

    Wagner Shin Nishitani

    Full Text Available A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7 expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

  5. Optimization of an innovative approach involving mechanical activation and acid digestion for the extraction of lithium from lepidolite

    Science.gov (United States)

    Vieceli, Nathália; Nogueira, Carlos A.; Pereira, Manuel F. C.; Durão, Fernando O.; Guimarães, Carlos; Margarido, Fernanda

    2018-01-01

    The recovery of lithium from hard rock minerals has received increased attention given the high demand for this element. Therefore, this study optimized an innovative process, which does not require a high-temperature calcination step, for lithium extraction from lepidolite. Mechanical activation and acid digestion were suggested as crucial process parameters, and experimental design and response-surface methodology were applied to model and optimize the proposed lithium extraction process. The promoting effect of amorphization and the formation of lithium sulfate hydrate on lithium extraction yield were assessed. Several factor combinations led to extraction yields that exceeded 90%, indicating that the proposed process is an effective approach for lithium recovery.

  6. Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

    DEFF Research Database (Denmark)

    Pingel, Jessica; Suhr, Frank

    2017-01-01

    mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young...... role in CP-related contractures. The aims of this review are (1) to summarize CP-related contracture mechanisms, (2) to raise novel hypotheses on the genesis of contractures with a focus on Cstms, and (3) to stimulate novel approaches to study CP-related contractures....

  7. Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes.

    Science.gov (United States)

    Turkseven, Saadet; Kruger, Adam; Mingone, Christopher J; Kaminski, Pawel; Inaba, Muneo; Rodella, Luigi F; Ikehara, Susumu; Wolin, Michael S; Abraham, Nader G

    2005-08-01

    Increased heme oxygenase (HO)-1 activity attenuates endothelial cell apoptosis and decreases superoxide anion (O2-) formation in experimental diabetes by unknown mechanisms. We examined the effect of HO-1 protein and HO activity on extracellular SOD (EC-SOD), catalase, O2-, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) levels and vascular responses to ACh in control and diabetic rats. Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats (P inhibitor of HO-1 activity, decreased EC-SOD protein. Increased HO-1 activity in diabetic rats was associated with a decrease in iNOS but increases in eNOS and plasma catalase activity. On the other hand, aortic ring segments from diabetic rats exhibited a significant reduction in vascular relaxation to ACh, which was reversed with cobalt protoporphyrin treatment. These data demonstrate that an increase in HO-1 protein and activity, i.e., CO and bilirubin production, in diabetic rats brings about a robust increase in EC-SOD, catalase, and eNOS with a concomitant increase in endothelial relaxation and a decrease in O2-. These observations in experimental diabetes suggest that the vascular cytoprotective mechanism of HO-1 against oxidative stress requires an increase in EC-SOD and catalase.

  8. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

    Science.gov (United States)

    Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-01-01

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

  9. The First Joke: Exploring the Evolutionary Origins of Humor

    Directory of Open Access Journals (Sweden)

    Joseph Polimeni

    2006-01-01

    Full Text Available Humor is a complex cognitive function which often leads to laughter. Contemporary humor theorists have begun to formulate hypotheses outlining the possible innate cognitive structures underlying humor. Humor's conspicuous presence in the behavioral repertoire of humankind invites adaptive explanations. This article explores the possible adaptive features of humor and ponders its evolutionary path through hominid history. Current humor theories and previous evolutionary ideas on humor are reviewed. In addition, scientific fields germane to the evolutionary study of humor are examined: animal models, genetics, children's humor, humor in pathological conditions, neurobiology, humor in traditional societies and cognitive archeology. Candidate selection pressures and associated evolutionary mechanisms are considered. The authors conclude that several evolutionary-related topics such as the origins of language, cognition underlying spiritual feelings, hominid group size, and primate teasing could have special relevance to the origins of humor.

  10. Probability Weighting as Evolutionary Second-best

    OpenAIRE

    Herold, Florian; Netzer, Nick

    2011-01-01

    The economic concept of the second-best involves the idea that multiple simultaneous deviations from a hypothetical first-best optimum may be optimal once the first-best itself can no longer be achieved, since one distortion may partially compensate for another. Within an evolutionary framework, we translate this concept to behavior under uncertainty. We argue that the two main components of prospect theory, the value function and the probability weighting function, are complements in the sec...

  11. Expanding Evolutionary Theory beyond Darwinism with Elaborating, Self-Organizing, and Fractionating Complex Evolutionary Systems

    Science.gov (United States)

    Fichter, Lynn S.; Pyle, E. J.; Whitmeyer, S. J.

    2010-01-01

    Earth systems increase in complexity, diversity, and interconnectedness with time, driven by tectonic/solar energy that keeps the systems far from equilibrium. The evolution of Earth systems is facilitated by three evolutionary mechanisms: "elaboration," "fractionation," and "self-organization," that share…

  12. Genomic signatures of evolutionary transitions from solitary to group living

    Science.gov (United States)

    Kapheim, Karen M.; Pan, Hailin; Li, Cai; Salzberg, Steven L.; Puiu, Daniela; Magoc, Tanja; Robertson, Hugh M.; Hudson, Matthew E.; Venkat, Aarti; Fischman, Brielle J.; Hernandez, Alvaro; Yandell, Mark; Ence, Daniel; Holt, Carson; Yocum, George D.; Kemp, William P.; Bosch, Jordi; Waterhouse, Robert M.; Zdobnov, Evgeny M.; Stolle, Eckart; Kraus, F. Bernhard; Helbing, Sophie; Moritz, Robin F. A.; Glastad, Karl M.; Hunt, Brendan G.; Goodisman, Michael A. D.; Hauser, Frank; Grimmelikhuijzen, Cornelis J. P.; Pinheiro, Daniel Guariz; Nunes, Francis Morais Franco; Soares, Michelle Prioli Miranda; Tanaka, Érica Donato; Simões, Zilá Luz Paulino; Hartfelder, Klaus; Evans, Jay D.; Barribeau, Seth M.; Johnson, Reed M.; Massey, Jonathan H.; Southey, Bruce R.; Hasselmann, Martin; Hamacher, Daniel; Biewer, Matthias; Kent, Clement F.; Zayed, Amro; Blatti, Charles; Sinha, Saurabh; Johnston, J. Spencer; Hanrahan, Shawn J.; Kocher, Sarah D.; Wang, Jun; Robinson, Gene E.; Zhang, Guojie

    2017-01-01

    The evolution of eusociality is one of the major transitions in evolution, but the underlying genomic changes are unknown. We compared the genomes of 10 bee species that vary in social complexity, representing multiple independent transitions in social evolution, and report three major findings. First, many important genes show evidence of neutral evolution as a consequence of relaxed selection with increasing social complexity. Second, there is no single road map to eusociality; independent evolutionary transitions in sociality have independent genetic underpinnings. Third, though clearly independent in detail, these transitions do have similar general features, including an increase in constrained protein evolution accompanied by increases in the potential for gene regulation and decreases in diversity and abundance of transposable elements. Eusociality may arise through different mechanisms each time, but would likely always involve an increase in the complexity of gene networks. PMID:25977371

  13. An evolutionary framework for cultural change: Selectionism versus communal exchange

    Science.gov (United States)

    Gabora, Liane

    2013-06-01

    Dawkins' replicator-based conception of evolution has led to widespread mis-application of selectionism across the social sciences because it does not address the paradox that necessitated the theory of natural selection in the first place: how do organisms accumulate change when traits acquired over their lifetime are obliterated? This is addressed by von Neumann's concept of a self-replicating automaton (SRA). A SRA consists of a self-assembly code that is used in two distinct ways: (1) actively deciphered during development to construct a self-similar replicant, and (2) passively copied to the replicant to ensure that it can reproduce. Information that is acquired over a lifetime is not transmitted to offspring, whereas information that is inherited during copying is transmitted. In cultural evolution there is no mechanism for discarding acquired change. Acquired change can accumulate orders of magnitude faster than, and quickly overwhelm, inherited change due to differential replication of variants in response to selection. This prohibits a selectionist but not an evolutionary framework for culture and the creative processes that fuel it. The importance non-Darwinian processes in biological evolution is increasingly recognized. Recent work on the origin of life suggests that early life evolved through a non-Darwinian process referred to as communal exchange that does not involve a self-assembly code, and that natural selection emerged from this more haphazard, ancestral evolutionary process. It is proposed that communal exchange provides an evolutionary framework for culture that enables specification of cognitive features necessary for a (real or artificial) societies to evolve culture. This is supported by a computational model of cultural evolution and a conceptual network based program for documenting material cultural history, and it is consistent with high levels of human cooperation.

  14. Modeling of Glycerol-3-Phosphate Transporter Suggests a Potential ‘Tilt’ Mechanism involved in its Function

    Science.gov (United States)

    Tsigelny, Igor F.; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K.

    2009-01-01

    Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane α-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family — the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY) — have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational “switching” mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible “switch” mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.23 We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a “tilt” of 9°–10° rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the “tilted” structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while

  15. Large-Scale Phylogenomic Analysis Reveals the Complex Evolutionary History of Rabies Virus in Multiple Carnivore Hosts.

    Directory of Open Access Journals (Sweden)

    Cécile Troupin

    2016-12-01

    Full Text Available The natural evolution of rabies virus (RABV provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence. Using 321 genome sequences spanning an unprecedented diversity of RABV, we compared evolutionary rates and selection pressures in viruses sampled from multiple primary host shifts that occurred on various continents. Two major phylogenetic groups, bat-related RABV and dog-related RABV, experiencing markedly different evolutionary dynamics were identified. While no correlation between time and genetic divergence was found in bat-related RABV, the evolution of dog-related RABV followed a generally clock-like structure, although with a relatively low evolutionary rate. Subsequent molecular clock dating indicated that dog-related RABV likely underwent a rapid global spread following the intensification of intercontinental trade starting in the 15th century. Strikingly, although dog RABV has jumped to various wildlife species from the order Carnivora, we found no clear evidence that these host-jumping events involved adaptive evolution, with RABV instead characterized by strong purifying selection, suggesting that ecological processes also play an important role in shaping patterns of emergence. However, specific amino acid changes were associated with the parallel emergence of RABV in ferret-badgers in Asia, and some host shifts were associated with increases in evolutionary rate, particularly in the ferret-badger and mongoose, implying that changes in host species can have important impacts on evolutionary dynamics.

  16. A possible mechanism of maxillofacial abscess formation: involvement of Porphyromonas endodontalis lipopolysaccharide via the expression of inflammatory cytokines.

    Science.gov (United States)

    Murakami, Y; Hanazawa, S; Tanaka, S; Iwahashi, H; Yamamoto, Y; Fujisawa, S

    2001-12-01

    In a previous study, we developed a specific monoclonal antibody against Porphyromonas endodontalis lipopolysaccharide, and demonstrated that this lipopolysaccharide was detected in bacterially infected root canal fluid. We suggest here that P. endodontalis lipopolysaccharide in the infectious materials plays a stimulatory role in maxillofacial abscess formation via the expression of inflammatory cytokines. Our epidemiological study showed that this lipopolysaccharide was detected in significant levels the infectious material of patients with periapical periodontitis and odontogenic abscesses. Interestingly, infectious material-induced expression of tumor necrosis factor-alpha, interleukin-1beta, or neutrophil chemoattractant KC genes in mouse macrophages, was significantly neutralized by monoclonal antibody against the lipopolysaccharide. In addition, we also detected a significant amount of tumor necrosis factor-alpha in the infectious material. These results suggest that P. endodontalis lipopolysaccharide plays an important role in the pathogenic mechanism of maxillofacial abscess formation via the expression of inflammatory cytokines.

  17. Studies in evolutionary agroecology

    DEFF Research Database (Denmark)

    Wille, Wibke

    of population performance will increase in frequency. Yield, one of the fundamental agronomic variables, is not an individual, but a population characteristic. A farmer wants a high yield per hectare; he is not interested in the performance of individual plants. When individual selection and population...... of Evolutionary Agroecology that the highest yielding individuals do not necessarily perform best as a population. The investment of resources into strategies and structures increasing individual competitive ability carries a cost. If a whole population consists of individuals investing resources to compete...

  18. Towards Adaptive Evolutionary Architecture

    DEFF Research Database (Denmark)

    Bak, Sebastian HOlt; Rask, Nina; Risi, Sebastian

    2016-01-01

    This paper presents first results from an interdisciplinary project, in which the fields of architecture, philosophy and artificial life are combined to explore possible futures of architecture. Through an interactive evolutionary installation, called EvoCurtain, we investigate aspects of how...... to the development of designs tailored to the individual preferences of inhabitants, changing the roles of architects and designers entirely. Architecture-as-it-could-be is a philosophical approach conducted through artistic methods to anticipate the technological futures of human-centered development within...

  19. Evolutionary primacy of sodium bioenergetics

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2008-04-01

    Full Text Available Abstract Background The F- and V-type ATPases are rotary molecular machines that couple translocation of protons or sodium ions across the membrane to the synthesis or hydrolysis of ATP. Both the F-type (found in most bacteria and eukaryotic mitochondria and chloroplasts and V-type (found in archaea, some bacteria, and eukaryotic vacuoles ATPases can translocate either protons or sodium ions. The prevalent proton-dependent ATPases are generally viewed as the primary form of the enzyme whereas the sodium-translocating ATPases of some prokaryotes are usually construed as an exotic adaptation to survival in extreme environments. Results We combine structural and phylogenetic analyses to clarify the evolutionary relation between the proton- and sodium-translocating ATPases. A comparison of the structures of the membrane-embedded oligomeric proteolipid rings of sodium-dependent F- and V-ATPases reveals nearly identical sets of amino acids involved in sodium binding. We show that the sodium-dependent ATPases are scattered among proton-dependent ATPases in both the F- and the V-branches of the phylogenetic tree. Conclusion Barring convergent emergence of the same set of ligands in several lineages, these findings indicate that the use of sodium gradient for ATP synthesis is the ancestral modality of membrane bioenergetics. Thus, a primitive, sodium-impermeable but proton-permeable cell membrane that harboured a set of sodium-transporting enzymes appears to have been the evolutionary predecessor of the more structurally demanding proton-tight membranes. The use of proton as the coupling ion appears to be a later innovation that emerged on several independent occasions. Reviewers This article was reviewed by J. Peter Gogarten, Martijn A. Huynen, and Igor B. Zhulin. For the full reviews, please go to the Reviewers' comments section.

  20. From simple receptors to complex multimodal percepts: a first global picture on the mechanisms involved in perceptual binding.

    Science.gov (United States)

    Velik, Rosemarie

    2012-01-01

    The binding problem in perception is concerned with answering the question how information from millions of sensory receptors, processed by millions of neurons working in parallel, can be merged into a unified percept. Binding in perception reaches from the lowest levels of feature binding up to the levels of multimodal binding of information coming from the different sensor modalities and also from other functional systems. The last 40 years of research have shown that the binding problem cannot be solved easily. Today, it is considered as one of the key questions to brain understanding. To date, various solutions have been suggested to the binding problem including: (1) combination coding, (2) binding by synchrony, (3) population coding, (4) binding by attention, (5) binding by knowledge, expectation, and memory, (6) hardwired vs. on-demand binding, (7) bundling and binding of features, (8) the feature-integration theory of attention, and (9) synchronization through top-down processes. Each of those hypotheses addresses important aspects of binding. However, each of them also suffers from certain weak points and can never give a complete explanation. This article gives a brief overview of the so far suggested solutions of perceptual binding and then shows that those are actually not mutually exclusive but can complement each other. A computationally verified model is presented which shows that, most likely, the different described mechanisms of binding act (1) at different hierarchical levels and (2) in different stages of "perceptual knowledge acquisition." The model furthermore considers and explains a number of inhibitory "filter mechanisms" that suppress the activation of inappropriate or currently irrelevant information.

  1. From simple receptors to complex multimodal percepts: A first global picture on the mechanisms involved in perceptual binding

    Directory of Open Access Journals (Sweden)

    Rosemarie eVelik

    2012-07-01

    Full Text Available The binding problem in perception is concerned with answering the question how information from millions of sensory receptors, processed by millions of neurons working in parallel, can be merged into a unified percept. Binding in perception reaches from the lowest levels of feature binding up to the levels of multimodal binding of information coming from the different sensor modalities and also from other functional systems. The last 40 years of research have shown that the binding problem cannot be solved easily. Today, it is considered as one of the key questions to brain understanding. To date, various solutions have been suggested to the binding problem including: (1 combination coding, (2 binding by synchrony, (3 population coding, (4 binding by attention, (5 binding by knowledge, expectation, and memory, (6 hardwired versus on-demand binding, (7 bundling and binding of features, (8 the feature-integration theory of attention, (9 synchronization through top-down processes. Each of those hypotheses addresses important aspects of binding. However, each of them also suffers from certain weak points and can never give a complete explanation. This article gives a brief overview of the so far suggested solutions of perceptual binding and then shows that those are actually not mutually exclusive but can complement each other. A computationally verified model is presented which shows that, most likely, the different described mechanisms of binding act (1 at different hierarchical levels and (2 in different stages of perceptual knowledge acquisition. The model furthermore considers and explains a number of inhibitory filter mechanisms that suppress the activation of inappropriate or currently irrelevant information.

  2. The involvement of topoisomerases and DNA polymerase I in the mechanism of induced thermal and radiation resistance in yeast

    International Nuclear Information System (INIS)

    Boreham, D.R.; Trivedi, A.; Weinberger, P.; Mitchel, R.E.

    1990-01-01

    Either an ionizing radiation exposure or a heat shock is capable of inducing both thermal tolerance and radiation resistance in yeast. Yeast mutants, deficient in topoisomerase I, in topoisomerase II, or in DNA polymerase I, were used to investigate the mechanism of these inducible resistances. The absence of either or both topoisomerase activities did not prevent induction of either heat or radiation resistance. However, if both topoisomerase I and II activities were absent, the sensitivity of yeast to become thermally tolerant (in response to a heat stress) was markedly increased. The absence of only topoisomerase I activity (top1) resulted in the constitutive expression of increased radiation resistance equivalent to that induced by a heat shock in wild-type cells, and the topoisomerase I-deficient cells were not further inducible by heat. This heat-inducible component of radiation resistance (or its equivalent constitutive expression in top1 cells) was, in turn, only a portion of the full response inducible by radiation. The absence of polymerase I activity had no detectable effect on either response. Our results indicate that the actual systems that confer resistance to heat or radiation are independent of either topoisomerase activity or DNA polymerase function, but suggest that topoisomerases may have a regulatory role during the signaling of these mechanisms. The results of our experiments imply that maintenance of correct DNA topology prevents induction of the heat-shock response, and that heat-shock induction of a component of the full radiation resistance in yeast may be the consequence of topoisomerase I inactivation

  3. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  4. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

    Directory of Open Access Journals (Sweden)

    Karin Voordeckers

    2015-11-01

    Full Text Available Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.

  5. Multiparty Evolutionary Game Model in Coal Mine Safety Management and Its Application

    Directory of Open Access Journals (Sweden)

    Rongwu Lu

    2018-01-01

    Full Text Available Coal mine safety management involves many interested parties and there are complex relationships between them. According to game theory, a multiparty evolutionary game model is established to analyze the selection of strategies. Then, a simplified three-party model is taken as an example to carry out detailed analysis and solution. Based on stability theory of dynamics system and phase diagram analysis, this article studies replicator dynamics of the evolutionary model to make an optimization analysis of the behaviors of those interested parties and the adjustment mechanism of safety management policies and decisions. The results show how the charge of supervision of government department and inspection of coal mine enterprise impact the efficiency of safety management and the effect of constraint measures and incentive and other measures in safety management.

  6. Can manipulations of cognitive load be used to test evolutionary hypotheses?

    Science.gov (United States)

    Barrett, H Clark; Frederick, David A; Haselton, Martie G; Kurzban, Robert

    2006-09-01

    D. DeSteno, M. Y. Bartlett, J. Braverman, and P. Salovey proposed that if sex-differentiated responses to infidelity are evolved, then they should be automatic, and therefore cognitive load should not attenuate them. DeSteno et al. found smaller sex differences in response to sexual versus emotional infidelity among participants under cognitive load, an effect interpreted as evidence against the evolutionary hypothesis. This logic is faulty. Cognitive load probably affects mechanisms involved in simulating infidelity experiences, thus seriously challenging the usefulness of cognitive load manipulations in testing hypotheses involving simulation. The method also entails the assumption that evolved jealousy mechanisms are necessarily automatic, an assumption not supported by theory or evidence. Regardless of how the jealousy debate is eventually settled, cognitive load manipulations cannot rule out the operation of evolved mechanisms. ((c) 2006 APA, all rights reserved).

  7. Tee-junction of LMFR secondary circuit involving thermal, thermomechanical and fracture mechanics assessment on a striping phenomenon

    International Nuclear Information System (INIS)

    Lee, H.-Y.; Kim, J.-B.; Yoo, B.

    2002-01-01

    This paper presents the thermomechanical and fracture mechanics evaluation procedure of thermal striping damage on the secondary piping of LMFR using Green's function method and standard FEM. The thermohydraulic loading conditions used in the present analysis are simplified sinusoidal thermal loads and the random type thermal loads. The thermomechanical fatigue damage was evaluated according to ASME code subsection NH. The results of fatigue analysis for the sinusoidal and random type load cases showed that fatigue failure would occur at a welded joint during 90 000 hours of operation. The assessment for the fracture behavior of the welded joint showed that the crack would be initiated at an early stage of the operation. The fatigue crack was evaluated to propagate up to 5 mm along the thickness direction during the first 940.7 and 42 698.9 hours of operation for the sinusoidal and the random loading cases, respectively. However, it was evaluated that the crack would be arrested because of the low level of the primary stresses. The fatigue and crack propagation analyses for the random type loads were performed by Green's function method. (author)

  8. Effect of Selenium on Control of Postharvest Gray Mold of Tomato Fruit and the Possible Mechanisms Involved

    Science.gov (United States)

    Wu, Zhilin; Yin, Xuebin; Bañuelos, Gary S.; Lin, Zhi-Qing; Zhu, Zhu; Liu, Ying; Yuan, Linxi; Li, Miao

    2016-01-01

    Selenium (Se) has important benefits for crop growth and stress tolerance at low concentrations. However, there is very little information on antimicrobial effect of Se against the economically important fungus Botrytis cinerea. In the present study, using sodium selenite as Se source, we investigated the effect of Se salts on spore germination and mycelial growth of the fungal pathogen in vitro and gray mold control in harvested tomato fruit. Se treatment at 24 mg/L significantly inhibited spore germination of the fungal pathogen and effectively controlled gray mold in harvested tomato fruit. Se treatment at 24 mg/L seems to induce the generation of intracellular reactive oxygen species in the fungal spores. The membrane integrity damage was observed with fluorescence microscopy following staining with propidium iodide after treatment of the spores with Se. These results suggest that Se has the potential for controlling gray mold rot of tomato fruits and might be useful in integrated control against gray mold disease of postharvest fruits and vegetables caused by B. cinerea. The mechanisms by which Se decreased gray mold decay of tomato fruit may be directly related to the severe damage to the conidia plasma membrane and loss of cytoplasmic materials from the hyphae. PMID:26779128

  9. Effect of selenium on control of postharvest gray mould of tomato fruit and the possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Zhilin eWu

    2016-01-01

    Full Text Available Selenium (Se has important benefits for crop growth and stress tolerance at low concentrations. However, there is very little information on antimicrobial effect of selenium against the economically important fungus Botrytis cinerea. In the present study, using sodium selenite as Se source, we investigated the effect of Se salts on spore germination and mycelial growth of the fungal pathogen in vitro and gray mould control in harvested tomato fruit. Se treatment at 24 mg/L significantly inhibited spore germination of the fungal pathogen and effectively controlled gray mould in harvested tomato fruit. Se treatment at 24 mg/L seems to induce the generation of intracellular reactive oxygen species in the fungal spores. The membrane integrity damage was observed with fluorescence microscopy following staining with propidium iodide after treatment of the spores with Se. These results suggest that Se has the potential for controlling gray mould rot of tomato fruits and might be useful in integrated control against gray mould disease of postharvest fruits and vegetables caused by B. cinerea. The mechanisms by which Se decreased gray mould decay of tomato fruit may be directly related to the severe damage to the conidia plasma membrane and loss of cytoplasmic materials from the hyphae.

  10. Possible Mechanisms of Mercury Toxicity and Cancer Promotion: Involvement of Gap Junction Intercellular Communications and Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Roberto Zefferino

    2017-01-01

    Full Text Available A number of observations indicate that heavy metals are able to alter cellular metabolic pathways through induction of a prooxidative state. Nevertheless, the outcome of heavy metal-mediated effects in the development of human diseases is debated and needs further insights. Cancer is a well-established DNA mutation-linked disease; however, epigenetic events are perhaps more important and harmful than genetic alterations. Unfortunately, we do not have reliable screening methods to assess/validate the epigenetic (promoter effects of a physical or a chemical agent. We propose a mechanism of action whereby mercury acts as a possible promoter carcinogen. In the present contribution, we resume our previous studies on mercury tested at concentrations comparable with its occurrence as environmental pollutant. It is shown that Hg(II elicits a prooxidative state in keratinocytes linked to inhibition of gap junction-mediated intercellular communication and proinflammatory cytokine production. These combined effects may on one hand isolate cells from tissue-specific homeostasis promoting their proliferation and on the other hand tamper the immune system defense/surveillance checkmating the whole organism. Since Hg(II is not a mutagenic/genotoxic compound directly affecting gene expression, in a broader sense, mercury might be an example of an epigenetic tumor promoter or, further expanding this concept, a “metagenetic” effector.

  11. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

    2014-01-17

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  12. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    International Nuclear Information System (INIS)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

    2014-01-01

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC

  13. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4

    Science.gov (United States)

    Semeraro, Fabrizio; Ammollo, Concetta T.; Morrissey, James H.; Dale, George L.; Friese, Paul; Esmon, Naomi L.

    2011-01-01

    The release of histones from dying cells is associated with microvascular thrombosis and, because histones activate platelets, this could represent a possible pathogenic mechanism. In the present study, we assessed the influence of histones on the procoagulant potential of human platelets in platelet-rich plasma (PRP) and in purified systems. Histones dose-dependently enhanced thrombin generation in PRP in the absence of any trigger, as evaluated by calibrated automated thrombinography regardless of whether the contact phase was inhibited. Activation of coagulation required the presence of fully activatable platelets and was not ascribable to platelet tissue factor, whereas targeting polyphosphate with phosphatase reduced thrombin generation even when factor XII (FXII) was blocked or absent. In the presence of histones, purified polyphosphate was able to induce thrombin generation in plasma independently of FXII. In purified systems, histones induced platelet aggregation; P-selectin, phosphatidylserine, and FV/Va expression; and prothrombinase activity. Blocking platelet TLR2 and TLR4 with mAbs reduced the percentage of activated platelets and lowered the amount of thrombin generated in PRP. These data show that histone-activated platelets possess a procoagulant phenotype that drives plasma thrombin generation and suggest that TLR2 and TLR4 mediate the activation process. PMID:21673343

  14. High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

    Directory of Open Access Journals (Sweden)

    Tarek A. M. Almabrouk

    2018-02-01

    Full Text Available Background and aim: Perivascular adipose tissue (PVAT positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD on aortic PVAT and whether any changes involved AMPK.Methods: Wild type Sv129 (WT and AMPKα1 knockout (KO mice aged 8 weeks were fed normal diet (ND or HFD (42% kcal fat for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later.Key results: Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markers Nos2 and Il1b and the M2 marker Chil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice.Conclusions: High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to

  15. Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency.

    Directory of Open Access Journals (Sweden)

    Mia Olsson

    Full Text Available Immunoglobulin A deficiency (IgAD is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei identified 35 genomic loci suggestively associated (p <0.0005 to IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9 were genome-wide significantly associated (p <0.0002 with IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005 to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development.

  16. Mechanism of plant-mediated synthesis of silver nanoparticles - A review on biomolecules involved, characterisation and antibacterial activity.

    Science.gov (United States)

    Rajeshkumar, S; Bharath, L V

    2017-08-01

    Engineering a reliable and eco-accommodating methodology for the synthesis of metal nanoparticles is a crucial step in the field of nanotechnology. Plant-mediated synthesis of metal nanoparticles has been developed as a substitute to defeat the limitations of conventional synthesis approaches such as physical and chemical methods. Biomolecules, such as proteins, amino acids, enzymes, flavonoids, and terpenoids from several plant extracts have been used as a stabilising and reducing agents for the synthesis of AgNPs. Regardless of an extensive range of biomolecules assistance in the synthesis procedure, researchers are facing a significant challenge to synthesise stable and geometrically controlled AgNPs. In the past decade, several efforts were made to develop Plant-mediated synthesis methods to produce stable, cost effective and eco-friendly AgNPs. More than hundred different plants extract sources for synthesising AgNPs were described in the last decade by several researchers. Most of the reviews were focused on various plant sources for synthesis, various characterization techniques for characteristic analysis, and antibacterial activity against bacterial. There are many reviews are available for the plant-mediated synthesis of AgNPs as well as antibacterial activity of AgNPs but this is the first review article mainly focused on biomolecules of plants and its various parts and operating conditions involved in the synthesis. Apart from, this review includes the characterisation of AgNPs and antibacterial activity of such nanoparticles with size, shape and method used for this study. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Core principles of evolutionary medicine

    Science.gov (United States)

    Grunspan, Daniel Z; Nesse, Randolph M; Barnes, M Elizabeth; Brownell, Sara E

    2018-01-01

    Abstract Background and objectives Evolutionary medicine is a rapidly growing field that uses the principles of evolutionary biology to better understand, prevent and treat disease, and that uses studies of disease to advance basic knowledge in evolutionary biology. Over-arching principles of evolutionary medicine have been described in publications, but our study is the first to systematically elicit core principles from a diverse panel of experts in evolutionary medicine. These principles should be useful to advance recent recommendations made by The Association of American Medical Colleges and the Howard Hughes Medical Institute to make evolutionary thinking a core competency for pre-medical education. Methodology The Delphi method was used to elicit and validate a list of core principles for evolutionary medicine. The study included four surveys administered in sequence to 56 expert panelists. The initial open-ended survey created a list of possible core principles; the three subsequent surveys winnowed the list and assessed the accuracy and importance of each principle. Results Fourteen core principles elicited at least 80% of the panelists to agree or strongly agree that they were important core principles for evolutionary medicine. These principles over-lapped with concepts discussed in other articles discussing key concepts in evolutionary medicine. Conclusions and implications This set of core principles will be helpful for researchers and instructors in evolutionary medicine. We recommend that evolutionary medicine instructors use the list of core principles to construct learning goals. Evolutionary medicine is a young field, so this list of core principles will likely change as the field develops further. PMID:29493660

  18. Practical advantages of evolutionary computation

    Science.gov (United States)

    Fogel, David B.

    1997-10-01

    Evolutionary computation is becoming a common technique for solving difficult, real-world problems in industry, medicine, and defense. This paper reviews some of the practical advantages to using evolutionary algorithms as compared with classic methods of optimization or artificial intelligence. Specific advantages include the flexibility of the procedures, as well as their ability to self-adapt the search for optimum solutions on the fly. As desktop computers increase in speed, the application of evolutionary algorithms will become routine.

  19. Behavioral and electrophysiological evidence for the mechanisms involved in the detection of ionizing radiations by the crayfish Pacifastacus trowbridgii

    International Nuclear Information System (INIS)

    Rodriguez, A.

    1976-01-01

    The light-adapted crayfish, Pacifastacus trowbridgii, displayed a behavioral response to exposure to 300 kV x-rays at exposure rates of 10 to 30 R/s. Within this range, the proportion of subjects that responded increased with an increase in exposure rate. The response latency was inversely proportional to the exposure rate. Ophthalmectomized animals exhibited a similar response with a significantly shorter latency than the intact animals at the same exposure rate (30 R/s). Partial body exposure of ophthalmectomized animals also elicited a behavioral response and indicated that a radiation-sensitive receptor was located in the abdomen. X-ray exposure of the dark-adapted compound eye evoked an electroretinogram (ERG) that was similar to the light evoked ERG. The x-ray evoked ERG amplitude was found to be dependent on total exposure for stimulus durations of 300 ms or less. With stimulus durations greater than 300 ms, the ERG amplitude increased in relation to the logarithm of the exposure rate. Similar responses with light indicated that the mechanism of interaction may be the same for x-rays. The time course for maximal dark-adaptation, after a 500 ms exposure to 3.85 ft-c of light, was comparable for both x-ray and light exposure (9 min). Differences observed in ERG amplitude between the light and x-ray evoked responses during the initial recovery period can be attributed to absorption of light by migrating accessory pigments or by differential interaction of light with photosensitive pigments in the eye

  20. The anxiolytic-like effect of 6-styryl-2-pyrone in mice involves GABAergic mechanism of action.

    Science.gov (United States)

    Chaves, Edna Maria Camelo; Honório-Júnior, Jose Eduardo Ribeiro; Sousa, Caren Nádia Soares; Monteiro, Valdécio Silveira; Nonato, Dayanne Terra Tenório; Dantas, Leonardo Pimentel; Lúcio, Ana Silvia Suassuna Carneiro; Barbosa-Filho, José Maria; Patrocínio, Manoel Cláudio Azevedo; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

    2018-02-01

    The present work aims to investigate the anxiolytic activity of 6-styryl-2-pyrone (STY), obtained from Aniba panurensis, in behavioral tests and amino acids dosage on male Swiss mice. The animals were treated with STY (1, 10 or 20 mg), diazepam (DZP 1 or 2 mg/kg) or imipramine (IMI 30 mg/kg). Some groups were administered with flumazenil, 30 min before administration of the STYor DZP. The behavioral tests performed were open field, rota rod, elevated plus maze (EPM), hole-board (HB) and tail suspension test (TST). After behavioral tests, these animals were sacrificed and had their prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) dissected for assaying amino acids (aspartate- ASP, glutamate- GLU, glycine- GLY, taurine- TAU and Gamma-aminobutyric acid- GABA). In EPM test, STY or DZP increased the number of entries and the time of permanence in the open arms, but these effects were reverted by flumazenil. In the HB test, STY increased the number of head dips however this effect was blocked by flumazenil. The effects of the STY on amino acid concentration in PFC showed increased GLU, GABA and TAU concentrations. In hippocampus, STY increased the concentrations of all amino acids studied. In striatum, STY administration at lowest dose reduced GLU concentrations, while the highest dosage caused the opposite effect. GLI, TAU and GABA concentrations increased with STY administration at highest doses. In conclusion, this study showed that STY presents an anxiolytic-like effect in behavioral tests that probably is related to GABAergic mechanism of action.

  1. The effect of maternal chromium status on lipid metabolism in female elderly mice offspring and involved molecular mechanism.

    Science.gov (United States)

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-04-30

    Maternal malnutrition leads to the incidence of metabolic diseases in offspring. The purpose of this project was to examine whether maternal low chromium could disturb normal lipid metabolism in offspring, altering adipose cell differentiation and leading to the incidence of lipid metabolism diseases, including metabolic syndrome and obesity. Female C57BL mice were given a control diet (CD) or a low chromium diet (LCD) during the gestational and lactation periods. After weaning, offspring was fed with CD or LCD. The female offspring were assessed at 32 weeks of age. Fresh adipose samples from CD-CD group and LCD-CD group were collected. Genome mRNA were analysed using Affymetrix GeneChip Mouse Gene 2.0 ST Whole Transcript-based array. Differentially expressed genes (DEGs) were analysed based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis database. Maternal low chromium irreversibly increased offspring body weight, fat-pad weight, serum triglyceride (TG) and TNF-α. Eighty five genes increased and 109 genes reduced in the offspring adipose of the maternal low chromium group. According to KEGG pathway and String analyses, the PPAR signalling pathway may be the key controlled pathway related to the effect of maternal low chromium on female offspring. Maternal chromium status have long-term effects of lipid metabolism in female mice offspring. Normalizing offspring diet can not reverse these effects. The potential underlying mechanisms are the disturbance of the PPAR signalling pathway in adipose tissue. © 2017 The Author(s).

  2. Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Jingru Zhao

    2016-04-01

    Full Text Available Although quorum-sensing (QS systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS. Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR, and its C-terminal HTH (helix-turn-helix domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator. Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

  3. Activation of rho is involved in the mechanism of hydrogen-peroxide-induced lung edema in isolated perfused rabbit lung.

    Science.gov (United States)

    Chiba, Y; Ishii, Y; Kitamura, S; Sugiyama, Y

    2001-09-01

    Acute lung injury is attributed primarily to increased vascular permeability caused by reactive oxygen species derived from neutrophils, such as hydrogen peroxide (H2O2). Increased permeability is accompanied by the contraction and cytoskeleton reorganization of endothelial cells, resulting in intercellular gap formation. The Rho family of Ras-like GTPases is implicated in the regulation of the cytoskeleton and cell contraction. We examined the role of Rho in H2O2-induced pulmonary edema with the use of isolated perfused rabbit lungs. To our knowledge, this is the first study to examine the role of Rho in increased vascular permeability induced by H2O2 in perfused lungs. Vascular permeability was evaluated on the basis of the capillary filtration coefficient (Kfc, ml/min/cm H2O/100 g). We found that H2O2 (300 microM) increased lung weight, Kfc, and pulmonary capillary pressure. These effects of H2O2 were abolished by treatment with Y-27632 (50 microM), an inhibitor of the Rho effector p160 ROCK. In contrast, the muscular relaxant papaverine inhibited the H2O2-induced rise in pulmonary capillary pressure, but did not suppress the increases in lung weight and Kfc. These findings indicate that H2O2 causes pulmonary edema by elevating hydrostatic pressure and increasing vascular permeability. Y-27632 inhibited the formation of pulmonary edema by blocking both of these H2O2-induced effects. Our results suggest that Rho-related pathways have a part in the mechanism of H2O2-induced pulmonary edema. Copyright 2001 Academic Press.

  4. Natural pedagogy as evolutionary adaptation.

    Science.gov (United States)

    Csibra, Gergely; Gergely, György

    2011-04-12

    We propose that the cognitive mechanisms that enable the transmission of cultural knowledge by communication between individuals constitute a system of 'natural pedagogy' in humans, and represent an evolutionary adaptation along the hominin lineage. We discuss three kinds of arguments that support this hypothesis. First, natural pedagogy is likely to be human-specific: while social learning and communication are both widespread in non-human animals, we know of no example of social learning by communication in any other species apart from humans. Second, natural pedagogy is universal: despite the huge variability in child-rearing practices, all human cultures rely on communication to transmit to novices a variety of different types of cultural knowledge, including information about artefact kinds, conventional behaviours, arbitrary referential symbols, cognitively opaque skills and know-how embedded in means-end actions. Third, the data available on early hominin technological culture are more compatible with the assumption that natural pedagogy was an independently selected adaptive cognitive system than considering it as a by-product of some other human-specific adaptation, such as language. By providing a qualitatively new type of social learning mechanism, natural pedagogy is not only the product but also one of the sources of the rich cultural heritage of our species.

  5. Natural pedagogy as evolutionary adaptation

    Science.gov (United States)

    Csibra, Gergely; Gergely, György

    2011-01-01

    We propose that the cognitive mechanisms that enable the transmission of cultural knowledge by communication between individuals constitute a system of ‘natural pedagogy’ in humans, and represent an evolutionary adaptation along the hominin lineage. We discuss three kinds of arguments that support this hypothesis. First, natural pedagogy is likely to be human-specific: while social learning and communication are both widespread in non-human animals, we know of no example of social learning by communication in any other species apart from humans. Second, natural pedagogy is universal: despite the huge variability in child-rearing practices, all human cultures rely on communication to transmit to novices a variety of different types of cultural knowledge, including information about artefact kinds, conventional behaviours, arbitrary referential symbols, cognitively opaque skills and know-how embedded in means-end actions. Third, the data available on early hominin technological culture are more compatible with the assumption that natural pedagogy was an independently selected adaptive cognitive system than considering it as a by-product of some other human-specific adaptation, such as language. By providing a qualitatively new type of social learning mechanism, natural pedagogy is not only the product but also one of the sources of the rich cultural heritage of our species. PMID:21357237

  6. A Neural Circuit Mechanism for the Involvements of Dopamine in Effort-Related Choices: Decay of Learned Values, Secondary Effects of Depletion, and Calculation of Temporal Difference Error

    Science.gov (United States)

    2018-01-01

    Abstract Dopamine has been suggested to be crucially involved in effort-related choices. Key findings are that dopamine depletion (i) changed preference for a high-cost, large-reward option to a low-cost, small-reward option, (ii) but not when the large-reward option was also low-cost or the small-reward option gave no reward, (iii) while increasing the latency in all the cases but only transiently, and (iv) that antagonism of either dopamine D1 or D2 receptors also specifically impaired selection of the high-cost, large-reward option. The underlying neural circuit mechanisms remain unclear. Here we show that findings i–iii can be explained by the dopaminergic representation of temporal-difference reward-prediction error (TD-RPE), whose mechanisms have now become clarified, if (1) the synaptic strengths storing the values of actions mildly decay in time and (2) the obtained-reward-representing excitatory input to dopamine neurons increases after dopamine depletion. The former is potentially caused by background neural activity–induced weak synaptic plasticity, and the latter is assumed to occur through post-depletion increase of neural activity in the pedunculopontine nucleus, where neurons representing obtained reward exist and presumably send excitatory projections to dopamine neurons. We further show that finding iv, which is nontrivial given the suggested distinct functions of the D1 and D2 corticostriatal pathways, can also be explained if we additionally assume a proposed mechanism of TD-RPE calculation, in which the D1 and D2 pathways encode the values of actions with a temporal difference. These results suggest a possible circuit mechanism for the involvements of dopamine in effort-related choices and, simultaneously, provide implications for the mechanisms of TD-RPE calculation. PMID:29468191

  7. Single turnover studies of oxidative halophenol dehalogenation by horseradish peroxidase reveal a mechanism involving two consecutive one electron steps: toward a functional halophenol bioremediation catalyst.

    Science.gov (United States)

    Sumithran, Suganya; Sono, Masanori; Raner, Gregory M; Dawson, John H

    2012-12-01

    Horseradish peroxidase (HRP) catalyzes the oxidative para-dechlorination of the environmental pollutant/carcinogen 2,4,6-trichlorophenol (2,4,6-TCP). A possible mechanism for this reaction is a direct oxygen atom transfer from HRP compound I (HRP I) to trichlorophenol to generate 2,6-dichloro 1,4-benzoquinone, a two-electron transfer process. An alternative mechanism involves two consecutive one-electron transfer steps in which HRP I is reduced to compound II (HRP II) and then to the ferric enzyme as first proposed by Wiese et al. [F.W. Wiese, H.C. Chang, R.V. Lloyd, J.P. Freeman, V.M. Samokyszyn, Arch. Environ. Contam. Toxicol. 34 (1998) 217-222]. To probe the mechanism of oxidative halophenol dehalogenation, the reactions between 2,4,6-TCP and HRP compounds I or II have been investigated under single turnover conditions (i.e., without excess H(2)O(2)) using rapid scan stopped-flow spectroscopy. Addition of 2,4,6-TCP to HRP I leads rapidly to HRP II and then more slowly to the ferric resting state, consistent with a mechanism involving two consecutive one-electron oxidations of the substrate via a phenoxy radical intermediate. HRP II can also directly dechlorinate 2,4,6-TCP as judged by rapid scan stopped-flow and mass spectrometry. This observation is particularly significant since HRP II can only carry out one-electron oxidations. A more detailed understanding of the mechanism of oxidative halophenol dehalogenation will facilitate the use of HRP as a halophenol bioremediation catalyst. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Invisible hand effect in an evolutionary minority game model

    Science.gov (United States)

    Sysi-Aho, Marko; Saramäki, Jari; Kaski, Kimmo

    2005-03-01

    In this paper, we study the properties of a minority game with evolution realized by using genetic crossover to modify fixed-length decision-making strategies of agents. Although the agents in this evolutionary game act selfishly by trying to maximize their own performances only, it turns out that the whole society will eventually be rewarded optimally. This “invisible hand” effect is what Adam Smith over two centuries ago expected to take place in the context of free market mechanism. However, this behaviour of the society of agents is realized only under idealized conditions, where all agents are utilizing the same efficient evolutionary mechanism. If on the other hand part of the agents are adaptive, but not evolutionary, the system does not reach optimum performance, which is also the case if part of the evolutionary agents form a uniformly acting “cartel”.

  9. Evolutionary design assistants for architecture

    Directory of Open Access Journals (Sweden)

    N. Onur Sönmez

    2015-04-01

    existing literature and the proposals and applications of the thesis; secondly, proposals for descriptive and prescriptive models, mappings, summary illustrations, task structures, decomposition schemes, and integratory frameworks; and finally, experimental applications of these proposals. This tripartite progression allows an evaluation of each proposal both conceptually and practically; thereby, enabling a progressive improvement of the understanding regarding the research question, while producing concrete outputs on the way. Besides theoretical and interpretative examinations, the thesis investigates its subject through a set of practical and speculative proposals, which function as both research instruments and the outputs of the study. The first main output of the study is the “design_proxy” approach (d_p, which is an integrated approach for draft making design assistants. It is an outcome of both theoretical examinations and experimental applications, and proposes an integration of, (1 flexible and relaxed task definitions and representations (instead of strict formalisms, (2 intuitive interfaces that make use of usual design media, (3 evaluation of solution proposals through their similarity to given examples, and (4 a dynamic evolutionary approach for solution generation. The design_proxy approach may be useful for AD researchers that aim at developing practical design assistants, as has been examined and demonstrated with the two applications, i.e., design_proxy.graphics and design_proxy.layout. The second main output, the “Interleaved Evolutionary Algorithm” (IEA, or Interleaved EA is a novel evolutionary algorithm proposed and used as the underlying generative mechanism of design_proxybased design assistants. The Interleaved EA is a dynamic, adaptive, and multi-objective EA, in which one of the objectives leads the evolution until its fitness progression stagnates; in the sense that the settings and fitness values of this objective is used for most

  10. Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats

    Directory of Open Access Journals (Sweden)

    Katagiri Ayano

    2012-03-01

    Full Text Available Abstract Background It has been reported that the P2Y12 receptor (P2Y12R is involved in satellite glial cells (SGCs activation, indicating that P2Y12R expressed in SGCs may play functional roles in orofacial neuropathic pain mechanisms. However, the involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown. We therefore studied the reflex to noxious mechanical or heat stimulation of the tongue, P2Y12R and glial fibrillary acidic protein (GFAP immunohistochemistries in the trigeminal ganglion (TG in a rat model of unilateral lingual nerve crush (LNC to evaluate role of P2Y12R in SGC in lingual neuropathic pain. Results The head-withdrawal reflex thresholds to mechanical and heat stimulation of the lateral tongue were significantly decreased in LNC-rats compared to sham-rats. These nocifensive effects were apparent on day 1 after LNC and lasted for 17 days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons encircled with GFAP-immunoreactive (IR cells significantly increased in the ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC, P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN-IR cells (i.e. neurons in TG. After 3 days of successive administration of the P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly decreased coincident with a significant reversal of the lowered head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue compared to vehicle-injected rats. Furthermore, after 3 days of successive administration of the P2YR agonist 2-MeSADP into the TG in naïve rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly increased and head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue were significantly decreased in a dose-dependent manner compared to vehicle-injected rats

  11. Spore: Spawning Evolutionary Misconceptions?

    Science.gov (United States)

    Bean, Thomas E.; Sinatra, Gale M.; Schrader, P. G.

    2010-10-01

    The use of computer simulations as educational tools may afford the means to develop understanding of evolution as a natural, emergent, and decentralized process. However, special consideration of developmental constraints on learning may be necessary when using these technologies. Specifically, the essentialist (biological forms possess an immutable essence), teleological (assignment of purpose to living things and/or parts of living things that may not be purposeful), and intentionality (assumption that events are caused by an intelligent agent) biases may be reinforced through the use of computer simulations, rather than addressed with instruction. We examine the video game Spore for its depiction of evolutionary content and its potential to reinforce these cognitive biases. In particular, we discuss three pedagogical strategies to mitigate weaknesses of Spore and other computer simulations: directly targeting misconceptions through refutational approaches, targeting specific principles of scientific inquiry, and directly addressing issues related to models as cognitive tools.

  12. Evolutionary games under incompetence.

    Science.gov (United States)

    Kleshnina, Maria; Filar, Jerzy A; Ejov, Vladimir; McKerral, Jody C

    2018-02-26

    The adaptation process of a species to a new environment is a significant area of study in biology. As part of natural selection, adaptation is a mutation process which improves survival skills and reproductive functions of species. Here, we investigate this process by combining the idea of incompetence with evolutionary game theory. In the sense of evolution, incompetence and training can be interpreted as a special learning process. With focus on the social side of the problem, we analyze the influence of incompetence on behavior of species. We introduce an incompetence parameter into a learning function in a single-population game and analyze its effect on the outcome of the replicator dynamics. Incompetence can change the outcome of the game and its dynamics, indicating its significance within what are inherently imperfect natural systems.

  13. Evolutionary Trajectories of Entomopathogenic Fungi ABC Transporters.

    Science.gov (United States)

    Baral, Bikash

    2017-01-01

    The ABC protein superfamily-also called traffic ATPases-are energy-dependent ubiquitous proteins, representing one of the crucial and the largest family in the fungal genomes. The ATP-binding cassette endows a characteristic 200-250 amino acids and is omnipresent in all organisms ranging from prokaryotes to eukaryotes. Unlike in bacteria with nutrient import functions, ABC transporters in fungal entomopathogens serve as effective efflux pumps that are largely involved in the shuttle of metabolites across the biological membranes. Thus, the search for ABC proteins may prove of immense importance in elucidating the functional and molecular mechanism at the host-pathogen (insect-fungus) interface. Their sequence homology, domain topology, and functional traits led to the actual identification of nine different families in fungal entomopathogens. Evolutionary relationships within the ABC superfamily are discussed, concentrating on computational approaches for comparative identification of ABC transporters in insect-pathogenic fungi (entomopathogens) with those of animals, plants, and their bacterial orthologs. Ancestors of some fungal candidates have duplicated extensively in some phyla, while others were lost in one lineage or the other, and predictions for the cause of their duplications and/or loss in some phyla are made. ABC transporters of fungal insect-pathogens serve both defensive and offensive functions effective against land-dwelling and ground foraging voracious insects. This study may help to unravel the molecular cascades of ABC proteins to illuminate the means through which insects cope with fungal infection and fungal-related diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The ectomycorrhizal fungus Paxillus involutus converts organic matter in plant litter using a trimmed brown-rot mechanism involving Fenton chemistry

    DEFF Research Database (Denmark)

    Rineau, Francois; Roth, Doris; Shah, Firoz

    2012-01-01

    chemistry similar to that of brown-rot fungi. The set of enzymes expressed by Pa. involutus during the degradation of the organic matter was similar to the set of enzymes involved in the oxidative degradation of wood by brown-rot fungi. However, Pa. involutus lacked transcripts encoding extracellular...... the mycorrhizal fungi. To capture the nitrogen, the fungi must at least partly disrupt the recalcitrant organic matterprotein complexes within which the nitrogen is embedded. This disruption process is poorly characterized. We used spectroscopic analyses and transcriptome profiling to examine the mechanism...... by which the ectomycorrhizal fungus Paxillus involutus degrades organic matter when acquiring nitrogen from plant litter. The fungus partially degraded polysaccharides and modified the structure of polyphenols. The observed chemical changes were consistent with a hydroxyl radical attack, involving Fenton...

  15. Is Exercise Really Medicine? An Evolutionary Perspective.

    Science.gov (United States)

    Lieberman, Daniel E

    2015-01-01

    An evolutionary perspective helps evaluate the extent to which exercise is medicine and to explain the exercise paradox: why people tend to avoid exercise despite its benefits. Many lines of evidence indicate that humans evolved to be adapted for regular, moderate amounts of endurance physical activity into late age. However, because energy from food was limited, humans also were selected to avoid unnecessary exertion, and most anatomical and physiological systems evolved to require stimuli from physical activity to adjust capacity to demand. Consequently, selection never operated to cope with the long-term effects of chronic inactivity. However, because all adaptations involve trade-offs, there is no evolutionary-determined dose or type of physical activity that will optimize health. Furthermore, because humans evolved to be active for play or necessity, efforts to promote exercise will require altering environments in ways that nudge or even compel people to be active and to make exercise fun.

  16. Molecular characterization of a genomic region in a Lactococcus bacteriophage that is involved in its sensitivity to the phage defense mechanism AbiA.

    OpenAIRE

    Dinsmore, P K; Klaenhammer, T R

    1997-01-01

    A spontaneous mutant of the lactococcal phage phi31 that is insensitive to the phage defense mechanism AbiA was characterized in an effort to identify the phage factor(s) involved in sensitivity of phi31 to AbiA. A point mutation was localized in the genome of the AbiA-insensitive phage (phi31A) by heteroduplex analysis of a 9-kb region. The mutation (G to T) was within a 738-bp open reading frame (ORF245) and resulted in an arginine-to-leucine change in the predicted amino acid sequence of t...

  17. Open Issues in Evolutionary Robotics.

    Science.gov (United States)

    Silva, Fernando; Duarte, Miguel; Correia, Luís; Oliveira, Sancho Moura; Christensen, Anders Lyhne

    2016-01-01

    One of the long-term goals in evolutionary robotics is to be able to automatically synthesize controllers for real autonomous robots based only on a task specification. While a number of studies have shown the applicability of evolutionary robotics techniques for the synthesis of behavioral control, researchers have consistently been faced with a number of issues preventing the widespread adoption of evolutionary robotics for engineering purposes. In this article, we review and discuss the open issues in evolutionary robotics. First, we analyze the benefits and challenges of simulation-based evolution and subsequent deployment of controllers versus evolution on real robotic hardware. Second, we discuss specific evolutionary computation issues that have plagued evolutionary robotics: (1) the bootstrap problem, (2) deception, and (3) the role of genomic encoding and genotype-phenotype mapping in the evolution of controllers for complex tasks. Finally, we address the absence of standard research practices in the field. We also discuss promising avenues of research. Our underlying motivation is the reduction of the current gap between evolutionary robotics and mainstream robotics, and the establishment of evolutionary robotics as a canonical approach for the engineering of autonomous robots.

  18. Evolutionary economics and industry location

    NARCIS (Netherlands)

    Boschma, R.A.; Frenken, K.

    2003-01-01

    This paper aims to provide the outlines of an evolutionary economic geography of industry location. We discuss two evolutionary explanations of industry location, that is, one that concentrates on spin-offs, and one that focuses attention on knowledge and agglomeration economies. We claim that both

  19. Contemporary issues in evolutionary biology

    Indian Academy of Sciences (India)

    We are delighted to bring to the readers, a set of peer-reviewed papers on evolutionary biology, published as a special issue of the Journal of Genetics. These papers emanated from ruminations upon and discussions at the Foundations of. Evolutionary Theory: the Ongoing Synthesis meeting at Coorg, India, in February ...

  20. Fixation Time for Evolutionary Graphs

    Science.gov (United States)

    Nie, Pu-Yan; Zhang, Pei-Ai

    Evolutionary graph theory (EGT) is recently proposed by Lieberman et al. in 2005. EGT is successful for explaining biological evolution and some social phenomena. It is extremely important to consider the time of fixation for EGT in many practical problems, including evolutionary theory and the evolution of cooperation. This study characterizes the time to asymptotically reach fixation.

  1. Applications of evolutionary economic geography

    NARCIS (Netherlands)

    Boschma, R.A.; Frenken, K.; Puranam, Krishna Kishore; Ravi Kumar Jain B., xx

    2008-01-01

    This paper is written as the first chapter of an edited volume on evolutionary economics and economic geography (Frenken, K., editor, Applied Evolutionary Economics and Economic Geography, Cheltenham: Edward Elgar, expected publication date February 2007). The paper reviews empirical applications of

  2. Neutral Evolution of Duplicated DNA: An Evolutionary Stick-Breaking Process Causes Scale-Invariant Behavior

    Science.gov (United States)

    Massip, Florian; Arndt, Peter F.

    2013-04-01

    Recently, an enrichment of identical matching sequences has been found in many eukaryotic genomes. Their length distribution exhibits a power law tail raising the question of what evolutionary mechanism or functional constraints would be able to shape this distribution. Here we introduce a simple and evolutionarily neutral model, which involves only point mutations and segmental duplications, and produces the same statistical features as observed for genomic data. Further, we extend a mathematical model for random stick breaking to analytically show that the exponent of the power law tail is -3 and universal as it does not depend on the microscopic details of the model.

  3. Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

    Science.gov (United States)

    Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

    2014-12-01

    Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

  4. The pangenome of (Antarctic) Pseudoalteromonas bacteria: evolutionary and functional insights.

    Science.gov (United States)

    Bosi, Emanuele; Fondi, Marco; Orlandini, Valerio; Perrin, Elena; Maida, Isabel; de Pascale, Donatella; Tutino, Maria Luisa; Parrilli, Ermenegilda; Lo Giudice, Angelina; Filloux, Alain; Fani, Renato

    2017-01-17

    Pseudoalteromonas is a genus of ubiquitous marine bacteria used as model organisms to study the biological mechanisms involved in the adaptation to cold conditions. A remarkable feature shared by these bacteria is their ability to produce secondary metabolites with a strong antimicrobial and antitumor activity. Despite their biotechnological relevance, representatives of this genus are still lacking (with few exceptions) an extensive genomic characterization, including features involved in the evolution of secondary metabolites production. Indeed, biotechnological applications would greatly benefit from such analysis. Here, we analyzed the genomes of 38 strains belonging to different Pseudoalteromonas species and isolated from diverse ecological niches, including extreme ones (i.e. Antarctica). These sequences were used to reconstruct the largest Pseudoalteromonas pangenome computed so far, including also the two main groups of Pseudoalteromonas strains (pigmented and not pigmented strains). The downstream analyses were conducted to describe the genomic diversity, both at genus and group levels. This allowed highlighting a remarkable genomic heterogeneity, even for closely related strains. We drafted all the main evolutionary steps that led to the current structure and gene content of Pseudoalteromonas representatives. These, most likely, included an extensive genome reduction and a strong contribution of Horizontal Gene Transfer (HGT), which affected biotechnologically relevant gene sets and occurred in a strain-specific fashion. Furthermore, this study also identified the genomic determinants related to some of the most interesting features of the Pseudoalteromonas representatives, such as the production of secondary metabolites, the adaptation to cold temperatures and the resistance to abiotic compounds. This study poses the bases for a comprehensive understanding of the evolutionary trajectories followed in time by this peculiar bacterial genus and for a

  5. Genotoxic potential of montmorillonite clay mineral and alteration in the expression of genes involved in toxicity mechanisms in the human hepatoma cell line HepG2.

    Science.gov (United States)

    Maisanaba, Sara; Hercog, Klara; Filipic, Metka; Jos, Ángeles; Zegura, Bojana

    2016-03-05

    Montmorillonite, also known as Cloisite(®)Na(+) (CNa(+)), is a natural clay with a wide range of well-documented and novel applications, such as pharmaceutical products or food packaging. Although considered a low toxic product, the expected increased exposure to CNa(+) arises concern on the potential consequences on human and environmental health especially as its genotoxicity has scarcely been investigated so far. Thus, we investigated, for the first time, the influence of non-cytotoxic concentrations of CNa(+) (15.65, 31.25 and 62.5 μg/mL) on genomic instability of human hepatoma cell line (HepG2) by determining the formation of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) with the Cytokinesis block micronucleus cytome assay. Further on we studied the influence of CNa(+) on the expression of several genes involved in toxicity mechanisms using the real-time quantitative PCR. The results showed that CNa(+) increased the number of MNi, while the numbers of NBUDs and NPBs were not affected. In addition it deregulated genes in all the groups studied, mainly after longer time of exposure. These findings provide the evidence that CNa(+) is potentially genotoxic. Therefore further studies that will elucidate the molecular mechanisms involved in toxic activity of CNa(+) are needed for hazard identification and human safety assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. 长期合作关系中惩罚机制的演化博弈分析%Evolutionary game analysis on punishment mechanism of long-term cooperative partnership

    Institute of Scientific and Technical Information of China (English)

    陈通; 罗晓彬; 汪勇杰

    2015-01-01

    In the public cultural PPP project management,establishing long-term cooperative partnership between construction unit and contractor will help reduce the cost of trust and acquire long-term gains.But some contractors take opportunistic be-havior by using information superiority for the pursuit of excess earnings and undermine the long-term cooperation condition. So,construction unit should take certain management tools to inhibit contractors’opportunistic behaviors.The inhibitory effect and necessity of the punishment mechanism for opportunistic behavior are investigated by establishing evolutionary game model and analyzing evolution path of the contractors’opportunistic behaviors in the long-term cooperation condition.The re-sults show that punishment mechanism does not play significant inhibitory role on the opportunistic behavior of the contractor under the condition of establishing long-term cooperative partnership in public cultural PPP projects.Based on this,construc-tion unit should fully communicate with the contractors to establish integrity and cooperation platform,and try to improve the potential long-term cooperative revenue through a variety of ways to achieve mutual benefit.%在公共文化 PPP 项目管理中,建设单位和承包商建立长期合作伙伴关系有助于降低信任成本,获得长期收益;但不排除承包商为追求超额收益,运用信息优势采取机会主义行为,破坏长期合作状态。因此,建设单位需采取一定的管理手段来抑制承包商的机会主义行为。运用演化博弈理论建立模型,分析承包商机会主义的演化路径,探讨在长期合作状态下,惩罚机制对承包商机会主义行为的抑制效果及其建立的必要性。结果表明,公共文化 PPP 项目中,在双方建立长期合作关系的前提下,惩罚机制对承包商的机会主义行为并未起到较为显著的抑制效果。基于此,建设单位应与承包商进行充分

  7. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad F Saeed

    2010-09-01

    Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

  8. A BDNF sensitive mechanism is involved in the fear memory resulting from the interaction between stress and the retrieval of an established trace.

    Science.gov (United States)

    Giachero, Marcelo; Bustos, Silvia G; Calfa, Gaston; Molina, Victor A

    2013-04-15

    The present study investigates the fear memory resulting from the interaction of a stressful experience and the retrieval of an established fear memory trace. Such a combination enhanced both fear expression and fear retention in adult Wistar rats. Likewise, midazolam intra-basolateral amygdala (BLA) infusion prior to stress attenuated the enhancement of fear memory thus suggesting the involvement of a stress-induced reduction of the GABAergic transmission in BLA in the stress-induced enhancing effect. It has been suggested that, unlike the immediate-early gene Zif268 which is related to the reconsolidation process, the expression of hippocampal brain-derived neurotrophic factor (BDNF) is highly correlated with consolidation. We therefore evaluate the relative contribution of these two neurobiological processes to the fear memory resulting from the above-mentioned interaction. Intra-dorsal hippocampus (DH) infusions of either the antisense Zif268 or the inhibitor of the protein degradation (Clasto-Lactacystin β-Lactone), suggested to be involved in the retrieval-dependent destabilization process, did not affect the resulting contextual memory. In contrast, the knockdown of hippocampal BDNF mitigated the stress-induced facilitating influence on fear retention. In addition, the retrieval experience elevated BDNF level in DH at 60 min after recall exclusively in stressed animals. These findings suggest the involvement of a hippocampal BDNF sensitive mechanism in the stress-promoting influence on the fear memory following retrieval.

  9. Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-Jun-N-terminal kinase signaling.

    Science.gov (United States)

    Eshraghi, Adrien A; Gupta, Chhavi; Van De Water, Thomas R; Bohorquez, Jorge E; Garnham, Carolyn; Bas, Esperanza; Talamo, Victoria Maria

    2013-03-01

    To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111. An animal model of cochlear implantation. Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT. ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae. Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  10. Mechanism for iron control of the Vibrio fischeri luminescence system: involvement of cyclic AMP and cyclic AMP receptor protein and modulation of DNA level.

    Science.gov (United States)

    Dunlap, P V

    1992-07-01

    Iron controls luminescence in Vibrio fischeri by an indirect but undefined mechanism. To gain insight into that mechanism, the involvement of cyclic AMP (cAMP) and cAMP receptor protein (CRP) and of modulation of DNA levels in iron control of luminescence were examined in V. fischeri and in Escherichia coli containing the cloned V. fischeri lux genes on plasmids. For V. fischeri and E. coli adenylate cyclase (cya) and CRP (crp) mutants containing intact lux genes (luxR luxICDABEG), presence of the iron chelator ethylenediamine-di(o-hydroxyphenyl acetic acid) (EDDHA) increased expression of the luminescence system like in the parent strains only in the cya mutants in the presence of added cAMP. In the E. coli strains containing a plasmid with a Mu dl(lacZ) fusion in luxR, levels of beta-galactosidase activity (expression from the luxR promoter) and luciferase activity (expression from the lux operon promoter) were both 2-3-fold higher in the presence of EDDHA in the parent strain, and for the mutants this response to EDDHA was observed only in the cya mutant in the presence of added cAMP. Therefore, cAMP and CRP are required for the iron restriction effect on luminescence, and their involvement in iron control apparently is distinct from the known differential control of transcription from the luxR and luxICDABEG promoters by cAMP-CRP. Furthermore, plasmid and chromosomal DNA levels were higher in E. coli and V. fischeri in the presence of EDDHA. The higher DNA levels correlated with an increase in expression of chromosomally encoded beta-galactosidase in E. coli and with a higher level of autoinducer in cultures of V. fischeri. These results implicate cAMP-CRP and modulation of DNA levels in the mechanism of iron control of the V. fischeri luminescence system.

  11. Chemical evolutionary games.

    Science.gov (United States)

    Aristotelous, Andreas C; Durrett, Richard

    2014-0